Skip to content
2000
image of Lipid Metabolism in Cerebral Ischemia: From Pathogenesis to Therapy
file format pdf download PDF

Abstract

Cerebral ischemia, a leading global cause of death and disability, is marked by multifaceted pathological processes through dysregulation of lipid metabolism. This review examines the pivotal role of lipid metabolism in the pathogenesis of cerebral ischemia, with a particular emphasis on its dual function in neuroinflammation and neuroprotection. It delves into the mechanisms by which Arachidonic Acid (AA) metabolites, such as prostaglandins and Leukotrienes (LTs), drive neuroinflammation through Cyclooxygenase (COX) and Lipoxygenase (LOX) pathways, exacerbating ischemic injury. Conversely, the aim was to review the therapeutic potential of Specialized Pro-resolving Mediators (SPMs), including lipoxins, Resolvins (RVs), and protectins, that resolve inflammation and promote tissue repair. In addition, the roles of Peroxisome Proliferator-Activated Receptors (PPARs) and sphingolipid signaling in modulating oxidative stress, mitochondrial dysfunction, and neuronal survival were also addressed. Integrating recent advances in lipid biology and cerebral ischemia research, this review presents an overview of the role of lipid metabolism in disease progression and its potential as a target for new therapeutic interventions. These findings bridge the gap between basic science and clinical research, opening new doors for the treatment of cerebral ischemia.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/cn/10.2174/011570159X389784250715064745
2025-07-23
2025-10-29

  • From This Site

    /content/journals/cn/10.2174/011570159X389784250715064745
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/cn/10.2174/011570159X389784250715064745/BMS-CN-2025-HT3-6363-9.html?itemId=/content/journals/cn/10.2174/011570159X389784250715064745&mimeType=html&fmt=ahah

References

  1. Feigin V.L. Stark B.A. Johnson C.O. Roth G.A. Bisignano C. Abady G.G. Abbasifard M. Abbasi-Kangevari M. Abd-Allah F. Abedi V. Abualhasan A. Abu-Rmeileh N.M.E. Abushouk A.I. Adebayo O.M. Agarwal G. Agasthi P. Ahinkorah B.O. Ahmad S. Ahmadi S. Ahmed Salih Y. Aji B. Akbarpour S. Akinyemi R.O. Al Hamad H. Alahdab F. Alif S.M. Alipour V. Aljunid S.M. Almustanyir S. Al-Raddadi R.M. Al-Shahi Salman R. Alvis-Guzman N. Ancuceanu R. Anderlini D. Anderson J.A. Ansar A. Antonazzo I.C. Arabloo J. Ärnlöv J. Artanti K.D. Aryan Z. Asgari S. Ashraf T. Athar M. Atreya A. Ausloos M. Baig A.A. Baltatu O.C. Banach M. Barboza M.A. Barker-Collo S.L. Bärnighausen T.W. Barone M.T.U. Basu S. Bazmandegan G. Beghi E. Beheshti M. Béjot Y. Bell A.W. Bennett D.A. Bensenor I.M. Bezabhe W.M. Bezabih Y.M. Bhagavathula A.S. Bhardwaj P. Bhattacharyya K. Bijani A. Bikbov B. Birhanu M.M. Boloor A. Bonny A. Brauer M. Brenner H. Global, regional, and national burden of stroke and its risk factors, 1990-2019: A systematic analysis for the global burden of disease study 2019. Lancet Neurol. 2021 20 10 795 820 10.1016/S1474‑4422(21)00252‑0 34487721
    [Google Scholar]
  2. China stroke prevention and treatment report 2021. Chin J. Cerebrovasc Dis. 2023 20 11 783 793
    [Google Scholar]
  3. Mao R. Zong N. Hu Y. Chen Y. Xu Y. Neuronal death mechanisms and therapeutic strategy in ischemic stroke. Neurosci. Bull. 2022 38 10 1229 1247 10.1007/s12264‑022‑00859‑0 35513682
    [Google Scholar]
  4. Tracey T.J. Steyn F.J. Wolvetang E.J. Ngo S.T. Neuronal lipid metabolism: Multiple pathways driving functional outcomes in health and disease. Front. Mol. Neurosci. 2018 11 10 10.3389/fnmol.2018.00010 29410613
    [Google Scholar]
  5. Kloska A. Malinowska M. Gabig-Cimińska, M.; Jakóbkiewicz-Banecka, J. Lipids and lipid mediators associated with the risk and pathology of ischemic stroke. Int. J. Mol. Sci. 2020 21 10 3618 10.3390/ijms21103618 32443889
    [Google Scholar]
  6. Ma Y. Chen Z. He Q. Guo Z.N. Yang Y. Liu F. Li F. Luo Q. Chang J. Spatiotemporal lipidomics reveals key features of brain lipid dynamic changes after cerebral ischemia and reperfusion therapy. Pharmacol. Res. 2022 185 106482 10.1016/j.phrs.2022.106482 36195305
    [Google Scholar]
  7. Hilkens N.A. Casolla B. Leung T.W. de Leeuw F.E. Stroke. Lancet 2024 403 10446 2820 2836 10.1016/S0140‑6736(24)00642‑1 38759664
    [Google Scholar]
  8. Easton J.D. Johnston S.C. Time to retire the concept of transient ischemic attack. JAMA 2022 327 9 813 814 10.1001/jama.2022.0300 35147656
    [Google Scholar]
  9. Washida K. Hattori Y. Ihara M. Animal models of chronic cerebral hypoperfusion: From mouse to primate. Int. J. Mol. Sci. 2019 20 24 6176 10.3390/ijms20246176 31817864
    [Google Scholar]
  10. Lipsanen A. Jolkkonen J. Experimental approaches to study functional recovery following cerebral ischemia. Cell. Mol. Life Sci. 2011 68 18 3007 3017 10.1007/s00018‑011‑0733‑3 21626271
    [Google Scholar]
  11. Babu M. Singh N. Datta A. In vitro oxygen glucose deprivation model of ischemic stroke: A proteomics-driven systems biological perspective. Mol. Neurobiol. 2022 59 4 2363 2377 10.1007/s12035‑022‑02745‑2 35080759
    [Google Scholar]
  12. Oxford Dictionary of Biochemistry and Molecular Biology. 2nd ed United Kingdom Oxford University Press 2024
    [Google Scholar]
  13. Fahy E. Subramaniam S. Murphy R.C. Nishijima M. Raetz C.R.H. Shimizu T. Spener F. van Meer G. Wakelam M.J.O. Dennis E.A. Update of the LIPID MAPS comprehensive classification system for lipids. J. Lipid Res. 2009 50 Suppl. S9 S14 10.1194/jlr.R800095‑JLR200 19098281
    [Google Scholar]
  14. Fahy E. Cotter D. Sud M. Subramaniam S. Lipid classification, structures and tools. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2011 1811 11 637 647 10.1016/j.bbalip.2011.06.009 21704189
    [Google Scholar]
  15. He S. Xu Z. Han X. Lipidome disruption in Alzheimer’s disease brain: Detection, pathological mechanisms, and therapeutic implications. Mol. Neurodegener. 2025 20 1 11 10.1186/s13024‑025‑00803‑6 39871348
    [Google Scholar]
  16. Farooqui A.A. Farooqui T. Phospholipids, sphingolipids, and cholesterol-derived lipid mediators and their role in neurological disorders. Int. J. Mol. Sci. 2024 25 19 10672 10.3390/ijms251910672 39409002
    [Google Scholar]
  17. Wang S. Soni K.G. Semache M. Casavant S. Fortier M. Pan L. Mitchell G.A. Lipolysis and the integrated physiology of lipid energy metabolism. Mol. Genet. Metab. 2008 95 3 117 126 10.1016/j.ymgme.2008.06.012 18762440
    [Google Scholar]
  18. Liu L. Liang J. Liu Y. Liu B. Dong X. Cai W. Zhang N. The Intersection of cerebral cholesterol metabolism and Alzheimer’s disease: Mechanisms and therapeutic prospects. Heliyon 2024 10 9 30523 10.1016/j.heliyon.2024.e30523 38726205
    [Google Scholar]
  19. Mencarelli C. Martinez-Martinez P. Ceramide function in the brain: when a slight tilt is enough. Cell. Mol. Life Sci. 2013 70 2 181 203 10.1007/s00018‑012‑1038‑x 22729185
    [Google Scholar]
  20. Okuno T. Gijón M.A. Zarini S. Martin S.A. Barkley R.M. Johnson C.A. Ohba M. Yokomizo T. Murphy R.C. Altered eicosanoid production and phospholipid remodeling during cell culture. J. Lipid Res. 2018 59 3 542 549 10.1194/jlr.M083030 29353239
    [Google Scholar]
  21. Yang L. Lv P. Ai W. Li L. Shen S. Nie H. Shan Y. Bai Y. Huang Y. Liu H. Lipidomic analysis of plasma in patients with lacunar infarction using normal-phase/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry. Anal. Bioanal. Chem. 2017 409 12 3211 3222 10.1007/s00216‑017‑0261‑6 28251292
    [Google Scholar]
  22. Sifat A.E. Nozohouri S. Archie S.R. Chowdhury E.A. Abbruscato T.J. Brain energy metabolism in ischemic stroke: Effects of smoking and diabetes. Int. J. Mol. Sci. 2022 23 15 8512 10.3390/ijms23158512 35955647
    [Google Scholar]
  23. Ebert D. Haller R.G. Walton M.E. Energy contribution of octanoate to intact rat brain metabolism measured by 13C nuclear magnetic resonance spectroscopy. J. Neurosci. 2003 23 13 5928 5935 10.1523/JNEUROSCI.23‑13‑05928.2003 12843297
    [Google Scholar]
  24. Zhang Y. Yin R. Research progress on the relationship between metabolites and clinical diagnosis and treatment of ischemic stroke. Chin J. Cerebrova Diseases 2021 18 12 870 875
    [Google Scholar]
  25. Wu Q.J. Tymianski M. Targeting NMDA receptors in stroke: New hope in neuroprotection. Mol. Brain 2018 11 1 15 10.1186/s13041‑018‑0357‑8 29534733
    [Google Scholar]
  26. Cen J. Liu L. He L. Liu M. Wang C.J. Ji B.S. N1 -(quinolin-2-ylmethyl)butane-1,4-diamine, a polyamine analogue, attenuated injury in in vitro and in vivo models of cerebral ischemia. Int. J. Dev. Neurosci. 2012 30 7 584 595 10.1016/j.ijdevneu.2012.08.008 22982502
    [Google Scholar]
  27. Schwertz D.W. Halverson J. Changes in phosphoinositide-specific phospholipase C and phospholipase A2 activity in ischemic and reperfused rat heart. Basic Res. Cardiol. 1992 87 2 113 127 10.1007/BF00801959 1590734
    [Google Scholar]
  28. Sun G.Y. Geng X. Teng T. Yang B. Appenteng M.K. Greenlief C.M. Lee J.C. Dynamic role of phospholipases A2 in health and diseases in the central nervous system. Cells 2021 10 11 2963 10.3390/cells10112963 34831185
    [Google Scholar]
  29. Bazan N.G. de Turco E.B.R. Allan G. Mediators of injury in neurotrauma: Intracellular signal transduction and gene expression. J. Neurotrauma 1995 12 5 791 814 10.1089/neu.1995.12.791 8594208
    [Google Scholar]
  30. Zheng L. Xie C. Zheng J. Dong Q. Si T. Zhang J. Hou S.T. An imbalanced ratio between PC(16:0/16:0) and LPC(16:0) revealed by lipidomics supports the role of the Lands cycle in ischemic brain injury. J. Biol. Chem. 2021 296 100151 10.1074/jbc.RA120.016565 33288676
    [Google Scholar]
  31. Rodriguez de Turco E.B. Belayev L. Liu Y. Busto R. Parkins N. Bazan N.G. Ginsberg M.D. Systemic fatty acid responses to transient focal cerebral ischemia: Influence of neuroprotectant therapy with human albumin. J. Neurochem. 2002 83 3 515 524 10.1046/j.1471‑4159.2002.01121.x 12390513
    [Google Scholar]
  32. Kinouchi H. Imaizumi S. Yoshimoto T. Yamamoto H. Motomiya M. Changes of polyphosphoinositides, lysophospholipid, and free fatty acids in transient cerebral ischemia of rat brain. Mol. Chem. Neuropathol. 1990 12 3 215 228 10.1007/BF03159946 1965409
    [Google Scholar]
  33. de Rodríguez Turco E.B. Cascone G.D. Pediconi M.F. Bazán N.G. Phosphatidate, phosphatidylinositol, diacylglycerols, and free fatty acids in the brain following electroshock, anoxia, or ischemia. Adv. Exp. Med. Biol. 1977 83 389 396 10.1007/978‑1‑4684‑3276‑3_36 920472
    [Google Scholar]
  34. Zhang J.P. Sun G.Y. Regulation of FFA by the acyltransferase pathway in focal cerebral ischemia-reperfusion. Neurochem. Res. 1995 20 11 1279 1286 10.1007/BF00992502 8786813
    [Google Scholar]
  35. Yoshida S. Ikeda M. Busto R. Santiso M. Martinez E. Ginsberg M.D. Cerebral phosphoinositide, triacylglycerol, and energy metabolism in reversible ischemia: origin and fate of free fatty acids. J. Neurochem. 1986 47 3 744 757 10.1111/j.1471‑4159.1986.tb00675.x 3016186
    [Google Scholar]
  36. Adibhatla R.M. Hatcher J.F. Dempsey R.J. Lipids and lipidomics in brain injury and diseases. AAPS J. 2006 8 2 E314 E321 10.1007/BF02854902 16796382
    [Google Scholar]
  37. Tian H. Qiu T. Zhao J. Li L. Guo J. Sphingomyelinase-induced ceramide production stimulate calcium-independent JNK and PP2A activation following cerebral ischemia. Brain Inj. 2009 23 13-14 1073 1080 10.3109/02699050903379388 19891536
    [Google Scholar]
  38. Kolesnick R.N. Krönke M. Regulation of ceramide production and apoptosis. Annu. Rev. Physiol. 1998 60 1 643 665 10.1146/annurev.physiol.60.1.643 9558480
    [Google Scholar]
  39. Perry D.K. Ceramide and apoptosis. Biochem. Soc. Trans. 1999 27 4 399 404 10.1042/bst0270399 10917610
    [Google Scholar]
  40. Bernoud-Hubac N. Lo Van A. Lazar A.N. Lagarde M. Ischemic brain injury: Involvement of lipids in the pathophysiology of stroke and therapeutic strategies. Antioxidants 2024 13 6 634 10.3390/antiox13060634 38929073
    [Google Scholar]
  41. Li Y. Wang Y. Yang W. Wu Z. Ma D. Sun J. Tao H. Ye Q. Liu J. Ma Z. Qiu L. Li W. Li L. Hu M. ROS-responsive exogenous functional mitochondria can rescue neural cells post-ischemic stroke. Front. Cell Dev. Biol. 2023 11 1207748 10.3389/fcell.2023.1207748 37465011
    [Google Scholar]
  42. Wang B. Wang Y. Zhang J. Hu C. Jiang J. Li Y. Peng Z. ROS-induced lipid peroxidation modulates cell death outcome: Mechanisms behind apoptosis, autophagy, and ferroptosis. Arch. Toxicol. 2023 97 6 1439 1451 10.1007/s00204‑023‑03476‑6 37127681
    [Google Scholar]
  43. Van Kuijk F.J.G.M. Holte L.L. Dratz E.A. 4-Hydroxyhexenal: A lipid peroxidation product derived from oxidized docosahexaenoic acid. Biochim. Biophys. Acta Lipids Lipid Metab. 1990 1043 1 116 118 10.1016/0005‑2760(90)90118‑H 2138035
    [Google Scholar]
  44. Saimoto Y. Kusakabe D. Morimoto K. Matsuoka Y. Kozakura E. Kato N. Tsunematsu K. Umeno T. Kiyotani T. Matsumoto S. Tsuji M. Hirayama T. Nagasawa H. Uchida K. Karasawa S. Jutanom M. Yamada K. Lysosomal lipid peroxidation contributes to ferroptosis induction via lysosomal membrane permeabilization. Nat. Commun. 2025 16 1 3554 10.1038/s41467‑025‑58909‑w 40229298
    [Google Scholar]
  45. Zheng Y. Sun J. Luo Z. Li Y. Huang Y. Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications. Cell Death Dis. 2024 15 11 859 10.1038/s41419‑024‑07244‑x 39587094
    [Google Scholar]
  46. Kumar S.S. Singh D. Mitochondrial mechanisms in cerebral ischemia-reperfusion injury: Unravelling the intricacies. Mitochondrion 2024 77 101883 10.1016/j.mito.2024.101883 38631511
    [Google Scholar]
  47. He J. Liu J. Huang Y. Tang X. Xiao H. Hu Z. Oxidative stress, inflammation, and autophagy: Potential targets of mesenchymal stem cells-based therapies in ischemic stroke. Front. Neurosci. 2021 15 641157 10.3389/fnins.2021.641157 33716657
    [Google Scholar]
  48. Ranneh Y. Ali F. Akim A.M. Hamid H.A. Khazaai H. Fadel A. Crosstalk between reactive oxygen species and pro-inflammatory markers in developing various chronic diseases: A review. Appl. Biol. Chem. 2017 60 3 327 338 10.1007/s13765‑017‑0285‑9
    [Google Scholar]
  49. Chen H. Chen X. Li W. Shen J. Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: Potential application for drug discovery. Acta Pharmacol. Sin. 2018 39 5 669 682 10.1038/aps.2018.27 29595191
    [Google Scholar]
  50. Stratigi K Chatzidoukaki O Garinis G A DNA damage-induced inflammation and nuclear architecture. Mech. Ageing Dev 2017 165 Pt A 17 26 10.1016/j.mad.2016.09.008 27702596
    [Google Scholar]
  51. Yu W. Tu Y. Long Z. Liu J. Kong D. Peng J. Wu H. Zheng G. Zhao J. Chen Y. Liu R. Li W. Hai C. Reactive oxygen species bridge the gap between chronic inflammation and tumor development. Oxid. Med. Cell. Longev. 2022 2022 1 2606928 10.1155/2022/2606928 35799889
    [Google Scholar]
  52. Alsbrook D.L. Di Napoli M. Bhatia K. Biller J. Andalib S. Hinduja A. Rodrigues R. Rodriguez M. Sabbagh S.Y. Selim M. Farahabadi M.H. Jafarli A. Divani A.A. Neuroinflammation in acute ischemic and hemorrhagic stroke. Curr. Neurol. Neurosci. Rep. 2023 23 8 407 431 10.1007/s11910‑023‑01282‑2 37395873
    [Google Scholar]
  53. Colląo-Moraes, Y.; Aspey, B.; Harrison, M.; de Belleroche, J. Cyclo-oxygenase-2 messenger RNA induction in focal cerebral ischemia. J. Cereb. Blood Flow Metab. 1996 16 6 1366 1372 10.1097/00004647‑199611000‑00035 8898713
    [Google Scholar]
  54. Iadecola C. Forster C. Nogawa S. Clark H.B. Ross M.E. Cyclooxygenase-2 immunoreactivity in the human brain following cerebral ischemia. Acta Neuropathol. 1999 98 1 9 14 10.1007/s004010051045 10412795
    [Google Scholar]
  55. Ahmad M. Graham S.H. Inflammation after stroke: Mechanisms and therapeutic approaches. Transl. Stroke Res. 2010 1 2 74 84 10.1007/s12975‑010‑0023‑7 20976117
    [Google Scholar]
  56. Gaudet R.J. Levine L. Effect of unilateral common carotid artery occlusion on levels of prostaglandins D2, F2 alpha and 6-keto-prostaglandin F1 alpha in gerbil brain. Stroke 1980 11 6 648 652 10.1161/01.STR.11.6.648 7210072
    [Google Scholar]
  57. Ikeda-Matsuo Y. Tanji H. Ota A. Hirayama Y. Uematsu S. Akira S. Sasaki Y. Microsomal prostaglandin E synthase-1 contributes to ischaemic excitotoxicity through prostaglandin E 2 EP 3 receptors. Br. J. Pharmacol. 2010 160 4 847 859 10.1111/j.1476‑5381.2010.00711.x 20590584
    [Google Scholar]
  58. Minamisawa H. Terashi A. Katayama Y. Kanda Y. Shimizu J. Shiratori T. Inamura K. Kaseki H. Yoshino Y. Brain eicosanoid levels in spontaneously hypertensive rats after ischemia with reperfusion: Leukotriene C4 as a possible cause of cerebral edema. Stroke 1988 19 3 372 377 10.1161/01.STR.19.3.372 3354024
    [Google Scholar]
  59. Wautier J.L. Wautier M.P. Pro- and anti-inflammatory prostaglandins and cytokines in humans: A mini review. Int. J. Mol. Sci. 2023 24 11 9647 10.3390/ijms24119647 37298597
    [Google Scholar]
  60. Wang B. Wu L. Chen J. Dong L. Chen C. Wen Z. Hu J. Fleming I. Wang D.W. Metabolism pathways of arachidonic acids: Mechanisms and potential therapeutic targets. Signal Transduct. Target. Ther. 2021 6 1 94 10.1038/s41392‑020‑00443‑w 33637672
    [Google Scholar]
  61. Rao A.M. Hatcher J.F. Kindy M.S. Dempsey R.J. Arachidonic acid and leukotriene C4: Role in transient cerebral ischemia of gerbils. Neurochem. Res. 1999 24 10 1225 1232 10.1023/A:1020916905312 10492517
    [Google Scholar]
  62. Jana B. Andronowska A. Całka, J.; Mówińska, A. Biosynthetic pathway for leukotrienes is stimulated by lipopolysaccharide and cytokines in pig endometrial stromal cells. Sci. Rep. 2025 15 1 2806 10.1038/s41598‑025‑86787‑1 39843578
    [Google Scholar]
  63. Yin P. Wei Y. Wang X. Zhu M. Feng J. Roles of specialized pro-resolving lipid mediators in cerebral ischemia reperfusion injury. Front. Neurol. 2018 9 617 10.3389/fneur.2018.00617 30131754
    [Google Scholar]
  64. Wu Y. Wang, Y-P.; Guo, P.; Ye, X-H.; Wang, J.; Yuan, S-Y.; Yao, S-L.; and Shang, Y. A lipoxin A4 analog ameliorates blood-brain barrier dysfunction and reduces MMP-9 expression in a rat model of focal cerebral ischemia-reperfusion injury. J. Mol. Neurosci. 2012 46 3 483 491 10.1007/s12031‑011‑9620‑5 21845429
    [Google Scholar]
  65. Sobrado M. Pereira M.P. Ballesteros I. Hurtado O. Fernández-López D. Pradillo J.M. Caso J.R. Vivancos J. Nombela F. Serena J. Lizasoain I. Moro M.A. Synthesis of lipoxin A4 by 5-lipoxygenase mediates PPARgamma-dependent, neuroprotective effects of rosiglitazone in experimental stroke. J. Neurosci. 2009 29 12 3875 3884 10.1523/JNEUROSCI.5529‑08.2009 19321784
    [Google Scholar]
  66. Bazan N.G. Eady T.N. Khoutorova L. Atkins K.D. Hong S. Lu Y. Zhang C. Jun B. Obenaus A. Fredman G. Zhu M. Winkler J.W. Petasis N.A. Serhan C.N. Belayev L. Novel aspirin-triggered neuroprotectin D1 attenuates cerebral ischemic injury after experimental stroke. Exp. Neurol. 2012 236 1 122 130 10.1016/j.expneurol.2012.04.007 22542947
    [Google Scholar]
  67. Chao H.C. Lee T.H. Chiang C.S. Yang S.Y. Kuo C.H. Tang S.C. Sphingolipidomics investigation of the temporal dynamics after ischemic brain injury. J. Proteome Res. 2019 18 9 3470 3478 10.1021/acs.jproteome.9b00370 31310127
    [Google Scholar]
  68. Spiegel S. Milstien S. Sphingosine-1-phosphate: An enigmatic signalling lipid. Nat. Rev. Mol. Cell Biol. 2003 4 5 397 407 10.1038/nrm1103 12728273
    [Google Scholar]
  69. Hasegawa Y. Suzuki H. Sozen T. Rolland W. Zhang J.H. Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats. Stroke 2010 41 2 368 374 10.1161/STROKEAHA.109.568899 19940275
    [Google Scholar]
  70. Spiegel S. Milstien S. Sphingosine 1-phosphate, a key cell signaling molecule. J. Biol. Chem. 2002 277 29 25851 25854 10.1074/jbc.R200007200 12011102
    [Google Scholar]
  71. Zhang S.Q. Xiao J. Chen M. Zhou L.Q. Shang K. Qin C. Tian D.S. Sphingosine-1-phosphate signaling in ischemic stroke: From bench to bedside and beyond. Front. Cell. Neurosci. 2021 15 781098 10.3389/fncel.2021.781098 34916911
    [Google Scholar]
  72. Sapkota A. Gaire B.P. Kang M.G. Choi J.W. S1P2 contributes to microglial activation and M1 polarization following cerebral ischemia through ERK1/2 and JNK. Sci. Rep. 2019 9 1 12106 10.1038/s41598‑019‑48609‑z 31431671
    [Google Scholar]
  73. Koh S.H. Park H.H. Neurogenesis in stroke recovery. Transl. Stroke Res. 2017 8 1 3 13 10.1007/s12975‑016‑0460‑z 26987852
    [Google Scholar]
  74. Martínez-Vila E. Irimia P. Challenges of neuroprotection and neurorestoration in ischemic stroke treatment. Cerebrovasc. Dis. 2005 20 Suppl. 2 148 158 10.1159/000089369 16327266
    [Google Scholar]
  75. Wall P.D. Egger M.D. Formation of new connexions in adult rat brains after partial deafferentation. Nature 1971 232 5312 542 545 10.1038/232542a0 4328622
    [Google Scholar]
  76. Rossini P.M. Calautti C. Pauri F. Baron J.C. Post-stroke plastic reorganisation in the adult brain. Lancet Neurol. 2003 2 8 493 502 10.1016/S1474‑4422(03)00485‑X 12878437
    [Google Scholar]
  77. Jones T.A. Schallert T. Overgrowth and pruning of dendrites in adult rats recovering from neocortical damage. Brain Res. 1992 581 1 156 160 10.1016/0006‑8993(92)90356‑E 1498666
    [Google Scholar]
  78. Ioannou M.S. Jackson J. Sheu S.H. Chang C.L. Weigel A.V. Liu H. Pasolli H.A. Xu C.S. Pang S. Matthies D. Hess H.F. Lippincott-Schwartz J. Liu Z. Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell 2019 177 6 1522 1535.e14 10.1016/j.cell.2019.04.001 31130380
    [Google Scholar]
  79. Chen Z.P. Wang S. Zhao X. Fang W. Wang Z. Ye H. Wang M.J. Ke L. Huang T. Lv P. Jiang X. Zhang Q. Li L. Xie S.T. Zhu J.N. Hang C. Chen D. Liu X. Yan C. Lipid-accumulated reactive astrocytes promote disease progression in epilepsy. Nat. Neurosci. 2023 26 4 542 554 10.1038/s41593‑023‑01288‑6 36941428
    [Google Scholar]
  80. Clain J. Couret D. Bringart M. Lecadieu A. Meilhac O. Lefebvre d’Hellencourt C. Diotel N. Metabolic disorders exacerbate the formation of glial scar after stroke. Eur. J. Neurosci. 2024 59 11 3009 3029 10.1111/ejn.16325 38576159
    [Google Scholar]
  81. García-Juan M. Villa M. Benito-Cuesta I. Ordóñez-Gutiérrez L. Wandosell F. Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system. Neural Regen. Res. 2025 20 11 3209 3210 10.4103/NRR.NRR‑D‑24‑00733 39715086
    [Google Scholar]
  82. Yamamoto H. Zhang S. Mizushima N. Autophagy genes in biology and disease. Nat. Rev. Genet. 2023 24 6 382 400 10.1038/s41576‑022‑00562‑w 36635405
    [Google Scholar]
  83. Chen Y. Deng H. Zhang N. Autophagy-targeting modulation to promote peripheral nerve regeneration. Neural Regen. Res. 2025 20 7 1864 1882 10.4103/NRR.NRR‑D‑23‑01948 39254547
    [Google Scholar]
  84. Ko S.H. Cho K.A. Li X. Ran Q. Liu Z. Chen L. GPX modulation promotes regenerative axonal fusion and functional recovery after injury through PSR-1 condensation. Nat. Commun. 2025 16 1 1079 10.1038/s41467‑025‑56382‑z 39870634
    [Google Scholar]
  85. Neumann B. Coakley S. Giordano-Santini R. Linton C. Lee E.S. Nakagawa A. Xue D. Hilliard M.A. EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway. Nature 2015 517 7533 219 222 10.1038/nature14102 25567286
    [Google Scholar]
  86. Sezgin E. Levental I. Mayor S. Eggeling C. The mystery of membrane organization: Composition, regulation and roles of lipid rafts. Nat. Rev. Mol. Cell Biol. 2017 18 6 361 374 10.1038/nrm.2017.16 28356571
    [Google Scholar]
  87. Tsui-Pierchala B.A. Encinas M. Milbrandt J. Johnson E.M. Lipid rafts in neuronal signaling and function. Trends Neurosci. 2002 25 8 412 417 10.1016/S0166‑2236(02)02215‑4 12127758
    [Google Scholar]
  88. Viljetić B.; Blažetić S.; Labak, I.; Ivić V.; Zjalić M.; Heffer, M.; Balog, M. Lipid rafts: The maestros of normal brain development. Biomolecules 2024 14 3 362 10.3390/biom14030362 38540780
    [Google Scholar]
  89. Sonnino S. Aureli M. Grassi S. Mauri L. Prioni S. Prinetti A. Lipid rafts in neurodegeneration and neuroprotection. Mol. Neurobiol. 2014 50 1 130 148 10.1007/s12035‑013‑8614‑4 24362851
    [Google Scholar]
  90. Grassi S. Giussani P. Mauri L. Prioni S. Sonnino S. Prinetti A. Lipid rafts and neurodegeneration: Structural and functional roles in physiologic aging and neurodegenerative diseases. J. Lipid Res. 2020 61 5 636 654 10.1194/jlr.TR119000427 31871065
    [Google Scholar]
  91. Hérincs Z. Corset V. Cahuzac N. Furne C. Castellani V. Hueber A.O. Mehlen P. DCC association with lipid rafts is required for netrin-1-mediated axon guidance. J. Cell Sci. 2005 118 8 1687 1692 10.1242/jcs.02296 15811950
    [Google Scholar]
  92. Xu N.J. Henkemeyer M. Ephrin reverse signaling in axon guidance and synaptogenesis. Semin. Cell Dev. Biol. 2012 23 1 58 64 10.1016/j.semcdb.2011.10.024 22044884
    [Google Scholar]
  93. Madwar C. Gopalakrishnan G. Lennox R.B. Lipid microdomains in synapse formation. ACS Chem. Neurosci. 2016 7 6 833 841 10.1021/acschemneuro.6b00058 27070205
    [Google Scholar]
  94. Pfrieger F.W. Role of cholesterol in synapse formation and function. Biochim. Biophys. Acta Biomembr. 2003 1610 2 271 280 10.1016/S0005‑2736(03)00024‑5 12648780
    [Google Scholar]
  95. Yasuda H. Kishiro K. Izumi N. Nakanishi M. Biphasic liberation of arachidonic and stearic acids during cerebral ischemia. J. Neurochem. 1985 45 1 168 172 10.1111/j.1471‑4159.1985.tb05489.x 2987409
    [Google Scholar]
  96. Reilly M.P. Lawson J.A. FitzGerald G.A. Eicosanoids and isoeicosanoids: Indices of cellular function and oxidant stress. J. Nutr. 1998 128 2 Suppl. 434S 438S 10.1093/jn/128.2.434S 9478043
    [Google Scholar]
  97. Abe K. Kogure K. Yamamoto H. Imazawa M. Miyamoto K. Mechanism of arachidonic acid liberation during ischemia in gerbil cerebral cortex. J. Neurochem. 1987 48 2 503 509 10.1111/j.1471‑4159.1987.tb04121.x 3794719
    [Google Scholar]
  98. McCoy J.M. Wicks J.R. Audoly L.P. The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis. J. Clin. Invest. 2002 110 5 651 658 10.1172/JCI0215528 12208866
    [Google Scholar]
  99. Nguyen M. Solle M. Audoly L.P. Tilley S.L. Stock J.L. McNeish J.D. Coffman T.M. Dombrowicz D. Koller B.H. Receptors and signaling mechanisms required for prostaglandin E2-mediated regulation of mast cell degranulation and IL-6 production. J. Immunol. 2002 169 8 4586 4593 10.4049/jimmunol.169.8.4586 12370397
    [Google Scholar]
  100. Kabashima K. Murata T. Tanaka H. Matsuoka T. Sakata D. Yoshida N. Katagiri K. Kinashi T. Tanaka T. Miyasaka M. Nagai H. Ushikubi F. Narumiya S. Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity. Nat. Immunol. 2003 4 7 694 701 10.1038/ni943 12778172
    [Google Scholar]
  101. Matsuoka T. Hirata M. Tanaka H. Takahashi Y. Murata T. Kabashima K. Sugimoto Y. Kobayashi T. Ushikubi F. Aze Y. Eguchi N. Urade Y. Yoshida N. Kimura K. Mizoguchi A. Honda Y. Nagai H. Narumiya S. Prostaglandin D2 as a mediator of allergic asthma. Science 2000 287 5460 2013 2017 10.1126/science.287.5460.2013 10720327
    [Google Scholar]
  102. Hirai H. Tanaka K. Yoshie O. Ogawa K. Kenmotsu K. Takamori Y. Ichimasa M. Sugamura K. Nakamura M. Takano S. Nagata K. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J. Exp. Med. 2001 193 2 255 262 10.1084/jem.193.2.255 11208866
    [Google Scholar]
  103. Sharma V. Sharma P. Singh T.G. Leukotriene signaling in neurodegeneration: Implications for treatment strategies. Inflammopharmacology 2024 32 6 3571 3584 10.1007/s10787‑024‑01557‑1 39167313
    [Google Scholar]
  104. Shabab T. Khanabdali R. Moghadamtousi S.Z. Kadir H.A. Mohan G. Neuroinflammation pathways: A general review. Int. J. Neurosci. 2017 127 7 624 633 10.1080/00207454.2016.1212854 27412492
    [Google Scholar]
  105. Szczuko M. Kozioł I.; Kotlęga, D.; Brodowski, J.; Drozd, A. The role of thromboxane in the course and treatment of ischemic stroke. Int. J. Mol. Sci. 2021 22 21 11644 10.3390/ijms222111644 34769074
    [Google Scholar]
  106. Xu G. Dong F. Su L. Tan Z.X. Lei M. Li L. Wen D. Zhang F. The role and therapeutic potential of nuclear factor κB (NF-κB) in ischemic stroke. Biomed. Pharmacother. 2024 171 116140 10.1016/j.biopha.2024.116140 38211425
    [Google Scholar]
  107. Griswold D.E. Adams J.L. Constitutive cyclooxygenase (COX-1) and inducible cyclooxygenase (COX-2): Rationale for selective inhibition and progress to date. Med. Res. Rev. 1996 16 2 181 206 10.1002/(SICI)1098‑1128(199603)16:2<181:AID‑MED3>3.0.CO;2‑X 8656779
    [Google Scholar]
  108. Li L. Sluter M.N. Yu Y. Jiang J. Prostaglandin E receptors as targets for ischemic stroke: Novel evidence and molecular mechanisms of efficacy. Pharmacol. Res. 2021 163 105238 10.1016/j.phrs.2020.105238 33053444
    [Google Scholar]
  109. Iadecola C. Sugimoto K. Niwa K. Kazama K. Ross M.E. Increased susceptibility to ischemic brain injury in cyclooxygenase-1-deficient mice. J. Cereb. Blood Flow Metab. 2001 21 12 1436 1441 10.1097/00004647‑200112000‑00008 11740205
    [Google Scholar]
  110. Nogawa S. Forster C. Zhang F. Nagayama M. Ross M.E. Iadecola C. Interaction between inducible nitric oxide synthase and cyclooxygenase-2 after cerebral ischemia. Proc. Natl. Acad. Sci. USA 1998 95 18 10966 10971 10.1073/pnas.95.18.10966 9724813
    [Google Scholar]
  111. Nakayama M. Uchimura K. Zhu R.L. Nagayama T. Rose M.E. Stetler R.A. Isakson P.C. Chen J. Graham S.H. Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia. Proc. Natl. Acad. Sci. USA 1998 95 18 10954 10959 10.1073/pnas.95.18.10954 9724811
    [Google Scholar]
  112. Jiang J. Dingledine R. Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection. Trends Pharmacol. Sci. 2013 34 7 413 423 10.1016/j.tips.2013.05.003 23796953
    [Google Scholar]
  113. Zhang Q. Wang Y. Zhu J. Zou M. Zhang Y. Wu H. Jin T. Specialized pro-resolving lipid mediators: A key player in resolving inflammation in autoimmune diseases. Sci. Bull. 2025 70 5 778 794 10.1016/j.scib.2024.07.049 39837719
    [Google Scholar]
  114. Julliard W.A. Myo Y.P.A. Perelas A. Jackson P.D. Thatcher T.H. Sime P.J. Specialized pro-resolving mediators as modulators of immune responses. Semin. Immunol. 2022 59 101605 10.1016/j.smim.2022.101605 35660338
    [Google Scholar]
  115. Fredman G. Serhan C.N. Specialized pro-resolving mediators in vascular inflammation and atherosclerotic cardiovascular disease. Nat. Rev. Cardiol. 2024 21 11 808 823 10.1038/s41569‑023‑00984‑x 38216693
    [Google Scholar]
  116. Wu L. Miao S. Zou L.B. Wu P. Hao H. Tang K. Zeng P. Xiong J. Li H.H. Wu Q. Cai L. Ye D.Y. Lipoxin A4 inhibits 5-lipoxygenase translocation and leukotrienes biosynthesis to exert a neuroprotective effect in cerebral ischemia/reperfusion injury. J. Mol. Neurosci. 2012 48 1 185 200 10.1007/s12031‑012‑9807‑4 22661361
    [Google Scholar]
  117. Vital S.A. Becker F. Holloway P.M. Russell J. Perretti M. Granger D.N. Gavins F.N.E. Formyl-peptide receptor 2/3/lipoxin A4 receptor regulates neutrophil-platelet aggregation and attenuates cerebral inflammation: Impact for therapy in cardiovascular disease. Circulation 2016 133 22 2169 2179 10.1161/CIRCULATIONAHA.115.020633 27154726
    [Google Scholar]
  118. Smith H.K. Gil C.D. Oliani S.M. Gavins F.N.E. Targeting formyl peptide receptor 2 reduces leukocyte-endothelial interactions in a murine model of stroke. FASEB J. 2015 29 5 2161 2171 10.1096/fj.14‑263160 25690650
    [Google Scholar]
  119. Wu L. Li H.H. Wu Q. Miao S. Liu Z.J. Wu P. Ye D.Y. Lipoxin A4 activates Nrf2 pathway and ameliorates cell damage in cultured cortical astrocytes exposed to oxygen-glucose deprivation/reperfusion insults. J. Mol. Neurosci. 2015 56 4 848 857 10.1007/s12031‑015‑0525‑6 25702137
    [Google Scholar]
  120. Serhan C.N. Chiang N. Dalli J. The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution. Semin. Immunol. 2015 27 3 200 215 10.1016/j.smim.2015.03.004 25857211
    [Google Scholar]
  121. Xian W. Wu Y. Xiong W. Li L. Li T. Pan S. Song L. Hu L. Pei L. Yao S. Shang Y. The pro-resolving lipid mediator Maresin 1 protects against cerebral ischemia/reperfusion injury by attenuating the pro-inflammatory response. Biochem. Biophys. Res. Commun. 2016 472 1 175 181 10.1016/j.bbrc.2016.02.090 26915798
    [Google Scholar]
  122. Zhang H. Feng Y. Si Y. Lu C. Wang J. Wang S. Li L. Xie W. Yue Z. Yong J. Dai S. Zhang L. Li X. Shank3 ameliorates neuronal injury after cerebral ischemia/reperfusion via inhibiting oxidative stress and inflammation. Redox Biol. 2024 69 102983 10.1016/j.redox.2023.102983 38064762
    [Google Scholar]
  123. Itoh K. Wakabayashi N. Katoh Y. Ishii T. Igarashi K. Engel J.D. Yamamoto M. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 1999 13 1 76 86 10.1101/gad.13.1.76 9887101
    [Google Scholar]
  124. Guo Z. Mo Z. Keap1-Nrf2 signaling pathway in angiogenesis and vascular diseases. J. Tissue Eng. Regen. Med. 2020 14 6 869 883 10.1002/term.3053 32336035
    [Google Scholar]
  125. Wu L. Liu Z.J. Miao S. Zou L.B. Cai L. Wu P. Ye D.Y. Wu Q. Li H.H. Lipoxin A4 ameliorates cerebral ischaemia/] reperfusion injury through upregulation of nuclear factor erythroid 2-related factor 2. Neurol. Res. 2013 35 9 968 975 10.1179/1743132813Y.0000000242 23880501
    [Google Scholar]
  126. Godson C. Mitchell S. Harvey K. Petasis N.A. Hogg N. Brady H.R. Cutting edge: Lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J. Immunol. 2000 164 4 1663 1667 10.4049/jimmunol.164.4.1663 10657608
    [Google Scholar]
  127. Ye X.H. Wu Y. Guo P.P. Wang J. Yuan S.Y. Shang Y. Yao S.L. Lipoxin A4 analogue protects brain and reduces inflammation in a rat model of focal cerebral ischemia reperfusion. Brain Res. 2010 1323 174 183 10.1016/j.brainres.2010.01.079 20138164
    [Google Scholar]
  128. Aubeux D. Tessier S. Pérez F. Geoffroy V. Gaudin A. In vitro phenotypic effects of Lipoxin A4 on M1 and M2 polarized macrophages derived from THP-1. Mol. Biol. Rep. 2023 50 1 339 348 10.1007/s11033‑022‑08041‑5 36331745
    [Google Scholar]
  129. Zirpoli H. Sosunov S.A. Niatsetskaya Z.V. Mayurasakorn K. Manual Kollareth D.J. Serhan C.N. Ten V.S. Deckelbaum R.J. NPD1 rapidly targets mitochondria-mediated apoptosis after acute injection protecting brain against ischemic injury. Exp. Neurol. 2021 335 113495 10.1016/j.expneurol.2020.113495 33038416
    [Google Scholar]
  130. Iwuchukwu I. Nguyen D. Shirazian A. Asatryan A. Jun B. Bazan N.G. Neuroprotectin D1, a lipid anti-inflammatory mediator, in patients with intracerebral hemorrhage. Biochimie 2022 195 16 18 10.1016/j.biochi.2021.12.017 34990771
    [Google Scholar]
  131. Zhao Q. Wu J. Lin Z. Hua Q. Zhang W. Ye L. Wu G. Du J. Xia J. Chu M. Hu X. Resolvin D1 alleviates the lung ischemia reperfusion injury via complement, immunoglobulin, TLR4, and inflammatory factors in rats. Inflammation 2016 39 4 1319 1333 10.1007/s10753‑016‑0364‑9 27145782
    [Google Scholar]
  132. Zhang T. Shu H.H. Chang L. Ye F. Xu K.Q. Huang W.Q. Resolvin D1 protects against hepatic ischemia/reperfusion injury in rats. Int. Immunopharmacol. 2015 28 1 322 327 10.1016/j.intimp.2015.06.017 26118631
    [Google Scholar]
  133. Basil M.C. Levy B.D. Specialized pro-resolving mediators: Endogenous regulators of infection and inflammation. Nat. Rev. Immunol. 2016 16 1 51 67 10.1038/nri.2015.4 26688348
    [Google Scholar]
  134. Latruffe N. Vamecq J. Peroxisome proliferators and peroxisome proliferator activated receptors (PPARs) as regulators of lipid metabolism. Biochimie 1997 79 2-3 81 94 10.1016/S0300‑9084(97)81496‑4 9209701
    [Google Scholar]
  135. Bordet R. Ouk T. Petrault O. Gelé P. Gautier S. Laprais M. Deplanque D. Duriez P. Staels B. Fruchart J.C. Bastide M. PPAR: A new pharmacological target for neuroprotection in stroke and neurodegenerative diseases. Biochem. Soc. Trans. 2006 34 6 1341 1346 10.1042/BST0341341 17073815
    [Google Scholar]
  136. Shehata A.H.F. Ahmed A.S.F. Abdelrehim A.B. Heeba G.H. The impact of single and combined PPAR-α and PPAR-γ activation on the neurological outcomes following cerebral ischemia reperfusion. Life Sci. 2020 252 117679 10.1016/j.lfs.2020.117679 32325134
    [Google Scholar]
  137. Boujon V. Uhlemann R. Wegner S. Wright M.B. Laufs U. Endres M. Kronenberg G. Gertz K. Dual PPAR α/γ agonist aleglitazar confers stroke protection in a model of mild focal brain ischemia in mice. J. Mol. Med. 2019 97 8 1127 1138 10.1007/s00109‑019‑01801‑0 31147725
    [Google Scholar]
  138. Kapadia R. Yi J.H. Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists. Front. Biosci. 2008 13 1813 1826
    [Google Scholar]
  139. Zolezzi J.M. Santos M.J. Bastías-Candia S. Pinto C. Godoy J.A. Inestrosa N.C. PPARs in the central nervous system: Roles in neurodegeneration and neuroinflammation. Biol. Rev. Camb. Philos. Soc. 2017 92 4 2046 2069 10.1111/brv.12320 28220655
    [Google Scholar]
  140. Titus C. Hoque M.T. Bendayan R. PPAR agonists for the treatment of neuroinflammatory diseases. Trends Pharmacol. Sci. 2024 45 1 9 23 10.1016/j.tips.2023.11.004 38065777
    [Google Scholar]
  141. Giampietro L. Gallorini M. De Filippis B. Amoroso R. Cataldi A. di Giacomo V. PPAR-γ agonist GL516 reduces oxidative stress and apoptosis occurrence in a rat astrocyte cell line. Neurochem. Int. 2019 126 239 245 10.1016/j.neuint.2019.03.021 30946848
    [Google Scholar]
  142. Chehaibi K. le Maire L. Bradoni S. Escola J.C. Blanco-Vaca F. Slimane M.N. Effect of PPAR-β/δ agonist GW0742 treatment in the acute phase response and blood-brain barrier permeability following brain injury. Transl. Res. 2017 182 27 48 10.1016/j.trsl.2016.10.004 27818230
    [Google Scholar]
  143. Li Q. Tian Z. Wang M. Kou J. Wang C. Rong X. Li J. Xie X. Pang X. Luteoloside attenuates neuroinflammation in focal cerebral ischemia in rats via regulation of the PPARγ/Nrf2/NF-κB signaling pathway. Int. Immunopharmacol. 2019 66 309 316 10.1016/j.intimp.2018.11.044 30502652
    [Google Scholar]
  144. Pardillo-Díaz R. Pérez-García P. Castro C. Nunez-Abades P. Carrascal L. Oxidative stress as a potential mechanism underlying membrane hyperexcitability in neurodegenerative diseases. Antioxidants 2022 11 8 1511 10.3390/antiox11081511 36009230
    [Google Scholar]
  145. Lv H. Jia S. Sun Y. Pang M. Lv E. Li X. Meng Q. Wang Y. Docosahexaenoic acid promotes M2 microglia phenotype via activating PPARγ-mediated ERK/AKT pathway against cerebral ischemia-reperfusion injury. Brain Res. Bull. 2023 199 110660 10.1016/j.brainresbull.2023.110660 37149267
    [Google Scholar]
  146. Gou Q. Jiang Y. Zhang R. Xu Y. Xu H. Zhang W. Shi J. Hou Y. PPARδ is a regulator of autophagy by its phosphorylation. Oncogene 2020 39 25 4844 4853 10.1038/s41388‑020‑1329‑x 32439863
    [Google Scholar]
  147. Hankin J.A. Farias S.E. Barkley R.M. Heidenreich K. Frey L.C. Hamazaki K. Kim H.Y. Murphy R.C. MALDI mass spectrometric imaging of lipids in rat brain injury models. J. Am Soc. Mass Spectrom 2011 22 6 s13361-011-0122-z 10.1007/s13361‑011‑0122‑z 21953042
    [Google Scholar]
  148. Nakane M. Kubota M. Nakagomi T. Tamura A. Hisaki H. Shimasaki H. Ueta N. Lethal forebrain ischemia stimulates sphingomyelin hydrolysis and ceramide generation in the gerbil hippocampus. Neurosci. Lett. 2000 296 2-3 89 92 10.1016/S0304‑3940(00)01655‑4 11108988
    [Google Scholar]
  149. Yu X.D. Wang J.W. Ceramide de novo synthesis in non-alcoholic fatty liver disease: Pathogenic mechanisms and therapeutic perspectives. Biochem. Pharmacol. 2022 202 115157 10.1016/j.bcp.2022.115157 35777449
    [Google Scholar]
  150. Mohamud Yusuf A. Hagemann N. Hermann D.M. The acid sphingomyelinase/ceramide system as target for ischemic stroke therapies. Neurosignals 2019 27 S1 32 43 10.33594/000000184 31778304
    [Google Scholar]
  151. Kawashima S. Yamashita T. Miwa Y. Ozaki M. Namiki M. Hirase T. Inoue N. Hirata K. Yokoyama M. HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats. Stroke 2003 34 1 157 163 10.1161/01.STR.0000048213.18751.52 12511768
    [Google Scholar]
  152. Saito T. Nito C. Ueda M. Inaba T. Kamiya F. Muraga K. Katsura K. Katayama Y. Continuous oral administration of atorvastatin ameliorates brain damage after transient focal ischemia in rats. Life Sci. 2014 94 2 106 114 10.1016/j.lfs.2013.11.018 24333133
    [Google Scholar]
  153. Yu Z.F. Nikolova-Karakashian M. Zhou D. Cheng G. Schuchman E.H. Mattson M.P. Pivotal role for acidic sphingomyelinase in cerebral ischemia-induced ceramide and cytokine production, and neuronal apoptosis. J. Mol. Neurosci. 2000 15 2 85 98 10.1385/JMN:15:2:85 11220788
    [Google Scholar]
  154. Novgorodov S.A. Riley C.L. Keffler J.A. Yu J. Kindy M.S. Macklin W.B. Lombard D.B. Gudz T.I. SIRT3 deacetylates ceramide synthases. J. Biol. Chem. 2016 291 4 1957 1973 10.1074/jbc.M115.668228 26620563
    [Google Scholar]
  155. Belayev L. Alonso O.F. Busto R. Zhao W. Ginsberg M.D. Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke 1996 27 9 1616 1623 10.1161/01.STR.27.9.1616 8784138
    [Google Scholar]
  156. Chen X. Shi C. He M. Xiong S. Xia X. Endoplasmic reticulum stress: Molecular mechanism and therapeutic targets. Signal Transduct. Target. Ther. 2023 8 1 352 10.1038/s41392‑023‑01570‑w 37709773
    [Google Scholar]
  157. Huang J. Chen L. Yao Z. Sun X. Tong X. Dong S. The role of mitochondrial dynamics in cerebral ischemia-reperfusion injury. Biomed. Pharmacother. 2023 162 114671 10.1016/j.biopha.2023.114671 37037094
    [Google Scholar]
  158. Veeresh P. Kaur H. Sarmah D. Mounica L. Verma G. Kotian V. Kesharwani R. Kalia K. Borah A. Wang X. Dave K.R. Rodriguez A.M. Yavagal D.R. Bhattacharya P. Endoplasmic reticulum-mitochondria crosstalk: From junction to function across neurological disorders. Ann. N. Y. Acad. Sci. 2019 1457 1 41 60 10.1111/nyas.14212 31460675
    [Google Scholar]
  159. Loew L.M. Carrington W. Tuft R.A. Fay F.S. Physiological cytosolic Ca²⁺ transients evoke concurrent mitochondrial depolarizations. Proc Natl Acad Sci U S A 1994 91 26 12579 12583 10.1073/pnas.91.26.12579 7809081
    [Google Scholar]
  160. Spencer T.L. See J.K. Bygrave F.L. Translocation and binding of adenine nucleotides by rat liver mitochondria partially depleted of phospholipids. Biochim. Biophys. Acta Bioenerg. 1976 423 3 365 373 10.1016/0005‑2728(76)90193‑6 1259954
    [Google Scholar]
  161. Sun D. Gilboe D.D. Ischemia-induced changes in cerebral mitochondrial free fatty acids, phospholipids, and respiration in the rat. J. Neurochem. 1994 62 5 1921 1928 10.1046/j.1471‑4159.1994.62051921.x 8158140
    [Google Scholar]
  162. Nakahara I. Kikuchi H. Taki W. Nishi S. Kito M. Yonekawa Y. Goto Y. Ogata N. Changes in major phospholipids of mitochondria during postischemic reperfusion in rat brain. J. Neurosurg. 1992 76 2 244 250 10.3171/jns.1992.76.2.0244 1309864
    [Google Scholar]
  163. Schwarzkopf T.M. Koch K. Klein J. Reduced severity of ischemic stroke and improvement of mitochondrial function after dietary treatment with the anaplerotic substance triheptanoin. Neuroscience 2015 300 201 209 10.1016/j.neuroscience.2015.05.014 25982559
    [Google Scholar]
  164. Yadollah-Damavandi S. Sharifi Z.N. Arani H.Z. Jangholi E. Karimi A. Parsa Y. Movassaghi S. Atorvastatin prevents the neuron loss in the hippocampal dentate gyrus region through its anti-oxidant and anti-apoptotic activities. CNS Neurol. Disord. Drug Targets 2021 20 1 76 86 10.2174/1871527319666200922160627 32962624
    [Google Scholar]
  165. Berressem D. Koch K. Franke N. Klein J. Eckert G.P. Intravenous treatment with a long-chain omega-3 lipid emulsion provides neuroprotection in a murine model of ischemic stroke - A pilot study. PLoS One 2016 11 11 0167329 10.1371/journal.pone.0167329 27902774
    [Google Scholar]
  166. Lara-Celador I. Castro-Ortega L. Álvarez A. Goñi-de-Cerio F. Lacalle J. Hilario E. Endocannabinoids reduce cerebral damage after hypoxic-ischemic injury in perinatal rats. Brain Res. 2012 1474 91 99 10.1016/j.brainres.2012.07.045 22841538
    [Google Scholar]
  167. Chen L. Chao Y. Cheng P. Li N. Zheng H. Yang Y. UPLC-QTOF/MS-based metabolomics reveals the protective mechanism of hydrogen on mice with ischemic stroke. Neurochem. Res. 2019 44 8 1950 1963 10.1007/s11064‑019‑02829‑x 31236794
    [Google Scholar]
  168. Chen T. Zhu Y. Jia J. Meng H. Xu C. Xian P. Li Z. Tang Z. Wu Y. Liu Y. Mitochondrial transplantation promotes remyelination and long-term locomotion recovery following cerebral ischemia. Mediators Inflamm. 2022 2022 1 8 10.1155/2022/1346343 36157892
    [Google Scholar]
  169. Murakami M. Taketomi Y. Miki Y. Sato H. Hirabayashi T. Yamamoto K. Recent progress in phospholipase A2 research: From cells to animals to humans. Prog. Lipid Res. 2011 50 2 152 192 10.1016/j.plipres.2010.12.001 21185866
    [Google Scholar]
  170. Farooqui A.A. Horrocks L.A. Farooqui T. Glycerophospholipids in brain: Their metabolism, incorporation into membranes, functions, and involvement in neurological disorders. Chem. Phys. Lipids 2000 106 1 1 29 10.1016/S0009‑3084(00)00128‑6 10878232
    [Google Scholar]
  171. Shoeb M. Ansari N. Srivastava S. Ramana K. 4-Hydroxynonenal in the pathogenesis and progression of human diseases. Curr. Med. Chem. 2013 21 2 230 237 10.2174/09298673113209990181 23848536
    [Google Scholar]
  172. Serhan C.N. Petasis N.A. Resolvins and protectins in inflammation resolution. Chem. Rev. 2011 111 10 5922 5943 10.1021/cr100396c 21766791
    [Google Scholar]
  173. Akbar M. Calderon F. Wen Z. Kim H.Y. Docosahexaenoic acid: A positive modulator of Akt signaling in neuronal survival. Proc. Natl. Acad. Sci. USA 2005 102 31 10858 10863 10.1073/pnas.0502903102 16040805
    [Google Scholar]
  174. Chomova M. Zitnanova I. Look into brain energy crisis and membrane pathophysiology in ischemia and reperfusion. Stress 2016 19 4 341 348 10.1080/10253890.2016.1174848 27095435
    [Google Scholar]
  175. Taguchi K. Motohashi H. Yamamoto M. Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells 2011 16 2 123 140 10.1111/j.1365‑2443.2010.01473.x 21251164
    [Google Scholar]
  176. Tan K. Fujimoto M. Takii R. Takaki E. Hayashida N. Nakai A. Mitochondrial SSBP1 protects cells from proteotoxic stresses by potentiating stress-induced HSF1 transcriptional activity. Nat. Commun. 2015 6 1 6580 10.1038/ncomms7580 25762445
    [Google Scholar]
  177. Xu S. Lu J. Shao A. Zhang J.H. Zhang J. Glial cells: Role of the immune response in ischemic stroke. Front. Immunol. 2020 11 294 10.3389/fimmu.2020.00294 32174916
    [Google Scholar]
  178. Anderson M.A. Burda J.E. Ren Y. Ao Y. O’Shea T.M. Kawaguchi R. Coppola G. Khakh B.S. Deming T.J. Sofroniew M.V. Astrocyte scar formation aids central nervous system axon regeneration. Nature 2016 532 7598 195 200 10.1038/nature17623 27027288
    [Google Scholar]
  179. Heppner F.L. Ransohoff R.M. Becher B. Immune attack: The role of inflammation in Alzheimer disease. Nat. Rev. Neurosci. 2015 16 6 358 372 10.1038/nrn3880 25991443
    [Google Scholar]
  180. Liddelow S.A. Guttenplan K.A. Clarke L.E. Bennett F.C. Bohlen C.J. Schirmer L. Bennett M.L. Münch A.E. Chung W.S. Peterson T.C. Wilton D.K. Frouin A. Napier B.A. Panicker N. Kumar M. Buckwalter M.S. Rowitch D.H. Dawson V.L. Dawson T.M. Stevens B. Barres B.A. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017 541 7638 481 487 10.1038/nature21029 28099414
    [Google Scholar]
  181. Wei H. Zhen L. Wang S. Zhang Y. Wang K. Jia P. Zhang Y. Wu Z. Yang Q. Hou W. Lv J. Zhang P. De novo lipogenesis in astrocytes promotes the repair of blood-brain barrier after transient cerebral ischemia through interleukin-33. Neuroscience 2022 481 85 98 10.1016/j.neuroscience.2021.11.026 34822949
    [Google Scholar]
  182. Liu Y. Li Y. Zhan M. Liu Y. Li Z. Li J. Cheng G. Teng G. Lu L. Astrocytic cytochrome P450 4A/20-hydroxyeicosate-traenoic acid contributes to angiogenesis in the experimental ischemic stroke. Brain Res. 2019 1708 160 170 10.1016/j.brainres.2018.12.023 30571981
    [Google Scholar]
  183. Sims N.R. Yew W.P. Reactive astrogliosis in stroke: Contributions of astrocytes to recovery of neurological function. Neurochem. Int. 2017 107 88 103 10.1016/j.neuint.2016.12.016 28057555
    [Google Scholar]
  184. Silver J. Miller J.H. Regeneration beyond the glial scar. Nat. Rev. Neurosci. 2004 5 2 146 156 10.1038/nrn1326 14735117
    [Google Scholar]
  185. Schönfeld P. Reiser G. Why does brain metabolism not favor burning of fatty acids to provide energy? Reflections on disadvantages of the use of free fatty acids as fuel for brain. J. Cereb. Blood Flow Metab. 2013 33 10 1493 1499 10.1038/jcbfm.2013.128 23921897
    [Google Scholar]
  186. Bélanger M. Magistretti P.J. The role of astroglia in neuroprotection. Dialogues Clin. Neurosci. 2009 11 3 281 295 10.31887/DCNS.2009.11.3/mbelanger 19877496
    [Google Scholar]
  187. Huang X.X. Li L. Jiang R.H. Yu J.B. Sun Y.Q. Shan J. Yang J. Ji J. Cheng S.Q. Dong Y.F. Zhang X.Y. Shi H.B. Liu S. Sun X.L. Lipidomic analysis identifies long-chain acylcarnitine as a target for ischemic stroke. J. Adv. Res. 2024 61 133 149 10.1016/j.jare.2023.08.007 37572732
    [Google Scholar]
  188. Wei H. Zhen L. Wang S. Yang L. Zhang S. Zhang Y. Jia P. Wang T. Wang K. Zhang Y. Ma L. Lv J. Zhang P. Glyceryl triacetate promotes blood-brain barrier recovery after ischemic stroke through lipogenesis-mediated IL-33 in mice. J. Neuroinflammation 2023 20 1 264 10.1186/s12974‑023‑02942‑3 37968698
    [Google Scholar]
  189. Avrova D.K. Bayunova L.V. Avrova N.F. Zakharova I.O. The effect of intranasal administration of gangliosides on the viability of CA1 hippocampal neurons in rat two-vessel occlusion model of forebrain ischemia/reperfusion injury. Bull. Exp. Biol. Med. 2024 176 6 736 742 10.1007/s10517‑024‑06099‑8 38907060
    [Google Scholar]
  190. Reid M.M. Belayev L. Khoutorova L. Mukherjee P.K. Obenaus A. Shelvin K. Knowles S. Hong S.H. Bazan N.G. Integrated inflammatory signaling landscape response after delivering Elovanoid free-fatty-acid precursors leading to experimental stroke neuroprotection. Sci. Rep. 2023 13 1 15841 10.1038/s41598‑023‑42126‑w 37740008
    [Google Scholar]
  191. Gao X. Zeb S. He Y.Y. Guo Y. Zhu Y.M. Zhou X.Y. Zhang H.L. Valproic acid inhibits glial scar formation after ischemic stroke. Pharmacology 2022 107 5-6 263 280 10.1159/000514951 35316816
    [Google Scholar]
  192. Turovsky E.A. Varlamova E.G. Gudkov S.V. Plotnikov E.Y. The protective mechanism of deuterated linoleic acid involves the activation of the Ca2+ signaling system of astrocytes in ischemia in vitro. Int. J. Mol. Sci. 2021 22 24 13216 10.3390/ijms222413216 34948013
    [Google Scholar]
  193. Xin W.Q. Wei W. Pan Y.L. Cui B.L. Yang X.Y. Bähr M. Doeppner T.R. Modulating poststroke inflammatory mechanisms: Novel aspects of mesenchymal stem cells, extracellular vesicles and microglia. World J. Stem Cells 2021 13 8 1030 1048 10.4252/wjsc.v13.i8.1030 34567423
    [Google Scholar]
  194. Xin W. Pan Y. Wei W. Tatenhorst L. Graf I. Popa-Wagner A. Gerner S.T. Huber S. Kilic E. Hermann D.M. Bähr M. Huttner H.B. Doeppner T.R. Preconditioned extracellular vesicles from hypoxic microglia reduce poststroke AQP4 depolarization, disturbed cerebrospinal fluid flow, astrogliosis, and neuroinflammation. Theranostics 2023 13 12 4197 4216 10.7150/thno.84059 37554272
    [Google Scholar]
  195. Hu X. Leak R.K. Shi Y. Suenaga J. Gao Y. Zheng P. Chen J. Microglial and macrophage polarization—new prospects for brain repair. Nat. Rev. Neurol. 2015 11 1 56 64 10.1038/nrneurol.2014.207 25385337
    [Google Scholar]
  196. Planas A.M. Role of microglia in stroke. Glia 2024 72 6 1016 1053 10.1002/glia.24501 38173414
    [Google Scholar]
  197. Arbaizar-Rovirosa M. Pedragosa J. Lozano J.J. Casal C. Pol A. Gallizioli M. Planas A.M. Aged lipid-laden microglia display impaired responses to stroke. EMBO Mol. Med. 2023 15 2 17175 10.15252/emmm.202217175 36541061
    [Google Scholar]
  198. Ghosh S. Castillo E. Frias E.S. Swanson R.A. Bioenergetic regulation of microglia. Glia 2018 66 6 1200 1212 10.1002/glia.23271 29219210
    [Google Scholar]
  199. O’Neill L.A.J. Kishton R.J. Rathmell J. A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 2016 16 9 553 565 10.1038/nri.2016.70 27396447
    [Google Scholar]
  200. Keren-Shaul H. Spinrad A. Weiner A. Matcovitch-Natan O. Dvir-Szternfeld R. Ulland T.K. David E. Baruch K. Lara-Astaiso D. Toth B. Itzkovitz S. Colonna M. Schwartz M. Amit I. A unique microglia type associated with restricting development of alzheimer’s disease. Cell 2017 169 7 1276 1290.e17 10.1016/j.cell.2017.05.018 28602351
    [Google Scholar]
  201. Beuker C. Schafflick D. Strecker J.K. Heming M. Li X. Wolbert J. Schmidt-Pogoda A. Thomas C. Kuhlmann T. Aranda-Pardos I. A-Gonzalez, N.; Kumar, P.A.; Werner, Y.; Kilic, E.; Hermann, D.M.; Wiendl, H.; Stumm, R.; Meyer zu Hörste, G.; Minnerup, J. Stroke induces disease-specific myeloid cells in the brain parenchyma and pia. Nat. Commun. 2022 13 1 945 10.1038/s41467‑022‑28593‑1 35177618
    [Google Scholar]
  202. Beccari S. Sierra-Torre V. Valero J. Pereira-Iglesias M. García-Zaballa M. Soria F.N. De Las Heras-Garcia L. Carretero-Guillen A. Capetillo-Zarate E. Domercq M. Huguet P.R. Ramonet D. Osman A. Han W. Dominguez C. Faust T.E. Touzani O. Pampliega O. Boya P. Schafer D. Mariño G. Canet-Soulas E. Blomgren K. Plaza-Zabala A. Sierra A. Microglial phagocytosis dysfunction in stroke is driven by energy depletion and induction of autophagy. Autophagy 2023 19 7 1952 1981 10.1080/15548627.2023.2165313 36622892
    [Google Scholar]
  203. Wei W. Lattau S.S.J. Xin W. Pan Y. Tatenhorst L. Zhang L. Graf I. Kuang Y. Zheng X. Hao Z. Popa-Wagner A. Gerner S.T. Huber S. Nietert M. Klose C. Kilic E. Hermann D.M. Bähr M. Huttner H.B. Liu H. Fitzner D. Doeppner T.R. Dynamic brain lipid profiles modulate microglial lipid droplet accumulation and inflammation under ischemic conditions in mice. Adv. Sci. 2024 11 41 2306863 10.1002/advs.202306863 39252446
    [Google Scholar]
  204. Wei W. Zhang L. Xin W. Pan Y. Tatenhorst L. Hao Z. Gerner S.T. Huber S. Juenemann M. Butz M. Huttner H.B. Bähr M. Fitzner D. Jia F. Doeppner T.R. TREM2 regulates microglial lipid droplet formation and represses post-ischemic brain injury. Biomed. Pharmacother. 2024 170 115962 10.1016/j.biopha.2023.115962 38042110
    [Google Scholar]
  205. Xue T. Ji J. Sun Y. Huang X. Cai Z. Yang J. Guo W. Guo R. Cheng H. Sun X. Sphingosine-1-phosphate, a novel TREM2 ligand, promotes microglial phagocytosis to protect against ischemic brain injury. Acta Pharm. Sin. B 2022 12 4 1885 1898 10.1016/j.apsb.2021.10.012 35847502
    [Google Scholar]
  206. Xin W. Pan Y. Wei W. Gerner S.T. Huber S. Juenemann M. Butz M. Bähr M. Huttner H.B. Doeppner T.R. TGF-β1 decreases microglia-mediated neuroinflammation and lipid droplet accumulation in an in vitro stroke model. Int. J. Mol. Sci. 2023 24 24 17329 10.3390/ijms242417329 38139158
    [Google Scholar]
  207. Cai W. Liu S. Hu M. Sun X. Qiu W. Zheng S. Hu X. Lu Z. Post-stroke DHA treatment protects against acute ischemic brain injury by skewing macrophage polarity toward the M2 phenotype. Transl. Stroke Res. 2018 9 6 669 680 10.1007/s12975‑018‑0662‑7 30203370
    [Google Scholar]
  208. Zhang Z.G. Chopp M. Neurorestorative therapies for stroke: Underlying mechanisms and translation to the clinic. Lancet Neurol. 2009 8 5 491 500 10.1016/S1474‑4422(09)70061‑4 19375666
    [Google Scholar]
  209. Song J. Cho K.J. Cheon S.Y. Kim S.H. Park K.A. Lee W.T. Lee J.E. Apoptosis signal-regulating kinase 1 (ASK1) is linked to neural stem cell differentiation after ischemic brain injury. Exp. Mol. Med. 2013 45 12 69 10.1038/emm.2013.134 24357833
    [Google Scholar]
  210. Chapman K.Z. Ge R. Monni E. Tatarishvili J. Ahlenius H. Arvidsson A. Ekdahl C.T. Lindvall O. Kokaia Z. Inflammation without neuronal death triggers striatal neurogenesis comparable to stroke. Neurobiol. Dis. 2015 83 1 15 10.1016/j.nbd.2015.08.013 26299391
    [Google Scholar]
  211. Butti E. Bacigaluppi M. Rossi S. Cambiaghi M. Bari M. Cebrian Silla A. Brambilla E. Musella A. De Ceglia R. Teneud L. De Chiara V. D’Adamo P. Garcia-Verdugo J.M. Comi G. Muzio L. Quattrini A. Leocani L. Maccarrone M. Centonze D. Martino G. Subventricular zone neural progenitors protect striatal neurons from glutamatergic excitotoxicity. Brain 2012 135 11 3320 3335 10.1093/brain/aws194 23008234
    [Google Scholar]
  212. Gao Y. Xie D. Wang Y. Niu L. Jiang H. Short-chain fatty acids reduce oligodendrocyte precursor cells loss by inhibiting the activation of astrocytes via the SGK1/IL-6 signalling pathway. Neurochem. Res. 2022 47 11 3476 3489 10.1007/s11064‑022‑03710‑0 36098889
    [Google Scholar]
  213. Ling L. Zhang S. Ji Z. Huang H. Yao G. Wang M. He R. Deng W. Fang L. Therapeutic effects of lipo-prostaglandin E1 on angiogenesis and neurogenesis after ischemic stroke in rats. Int. J. Neurosci. 2016 126 5 469 477 10.3109/00207454.2015.1031226 26000823
    [Google Scholar]
  214. Hu X. Zhang F. Leak R. Zhang W. Iwai M. Stetler R. Dai Y. Zhao A. Gao Y. Chen J. Transgenic overproduction of omega-3 polyunsaturated fatty acids provides neuroprotection and enhances endogenous neurogenesis after stroke. Curr. Mol. Med. 2013 13 9 1465 1473 10.2174/15665240113139990075 23971733
    [Google Scholar]
  215. Andrés C.M.C. Pérez de la Lastra J.M. Juan C.A. Plou F.J. Pérez-Lebeña E. Antioxidant metabolism pathways in vitamins, polyphenols, and selenium: Parallels and divergences. Int. J. Mol. Sci. 2024 25 5 2600 10.3390/ijms25052600 38473850
    [Google Scholar]
  216. Song Y. Bei Y. Xiao Y. Tong H.D. Wu X.Q. Chen M.T. Edaravone, a free radical scavenger, protects neuronal cells’ mitochondria from ischemia by inactivating another new critical factor of the 5-lipoxygenase pathway affecting the arachidonic acid metabolism. Brain Res. 2018 1690 96 104 10.1016/j.brainres.2018.03.006 29551652
    [Google Scholar]
  217. Zhang X. Zhang D. Zhong C. Li W. Dinesh-Kumar S.P. Zhang Y. Orchestrating ROS regulation: Coordinated post-translational modification switches in NADPH oxidases. New Phytol. 2025 245 2 510 522 10.1111/nph.20231 39468860
    [Google Scholar]
  218. Khaleqsefat E. Rasul K.H. Kheder R.K. Baban S. Baban J. Frameshift variation in the HMG-CoA reductase gene and unresponsiveness to cholesterol-lowering drugs in type 2 diabetes mellitus patients. Sci. Rep. 2025 15 1 288 10.1038/s41598‑024‑75461‑7 39747109
    [Google Scholar]
  219. Frankowski J.C. DeMars K.M. Ahmad A.S. Hawkins K.E. Yang C. Leclerc J.L. Doré S. Candelario-Jalil E. Detrimental role of the EP1 prostanoid receptor in blood-brain barrier damage following experimental ischemic stroke. Sci. Rep. 2015 5 1 17956 10.1038/srep17956 26648273
    [Google Scholar]
  220. Ibarrola D. Seegers H. Jaillard A. Hommel M. Décorps M. Massarelli R. The effect of eliprodil on the evolution of a focal cerebral ischaemia in vivo. Eur. J. Pharmacol. 1998 352 1 29 35 10.1016/S0014‑2999(98)00330‑6 9718264
    [Google Scholar]
  221. Ikeda-Matsuo Y. Tanji H. Narumiya S. Sasaki Y. Inhibition of prostaglandin E2 EP3 receptors improves stroke injury via anti-inflammatory and anti-apoptotic mechanisms. J. Neuroimmunol. 2011 238 1-2 34 43 10.1016/j.jneuroim.2011.06.014 21803432
    [Google Scholar]
  222. Liu M. Li H. Zhang L. Xu Z. Song Y. Wang X. Chu R. Xiao Y. Sun M. Ma Y. Mi W. Cottonseed oil alleviates ischemic stroke-induced oxidative stress injury via activating the Nrf2 signaling pathway. Mol. Neurobiol. 2021 58 6 2494 2507 10.1007/s12035‑020‑02256‑y 33443681
    [Google Scholar]
  223. Gureev A.P. Sadovnikova I.S. Chernyshova E.V. Tsvetkova A.D. Babenkova P.I. Nesterova V.V. Krutskikh E.P. Volodina D.E. Samoylova N.A. Andrianova N.V. Silachev D.N. Plotnikov E.Y. Beta-hydroxybutyrate mitigates sensorimotor and cognitive impairments in a photothrombosis-induced ischemic stroke in mice. Int. J. Mol. Sci. 2024 25 11 5710 10.3390/ijms25115710 38891898
    [Google Scholar]
  224. Bhattarai S. Sharma S. Ara H. Subedi U. Sun G. Li C. Bhuiyan M.S. Kevil C. Armstrong W.P. Minvielle M.T. Miriyala S. Panchatcharam M. Disrupted blood-brain barrier and mitochondrial impairment by autotaxin-lysophosphatidic acid axis in postischemic stroke. J. Am. Heart Assoc. 2021 10 18 021511 10.1161/JAHA.121.021511 34514847
    [Google Scholar]
  225. Bai F. Guo F. Jiang T. Wei H. Zhou H. Yin H. Zhong H. Xiong L. Wang Q. Arachidonyl-2-chloroethylamide alleviates cerebral ischemia injury through glycogen synthase kinase-3β-mediated mitochondrial biogenesis and functional improvement. Mol. Neurobiol. 2017 54 2 1240 1253 10.1007/s12035‑016‑9731‑7 26820679
    [Google Scholar]
  226. Anthony Jalin A.M.A. Rajasekaran M. Prather P.L. Kwon J.S. Gajulapati V. Choi Y. Kim C. Pahk K. Ju C. Kim W.K. Non-selective cannabinoid receptor antagonists, hinokiresinols reduce infiltration of microglia/macrophages into ischemic brain lesions in rat via modulating 2-arachidonolyglycerol-induced migration and mitochondrial activity. PLoS One 2015 10 10 0141600 10.1371/journal.pone.0141600 26517721
    [Google Scholar]
  227. Jiang D.T. Tuo L. Bai X. Bing W.D. Qu Q.X. Zhao X. Song G.M. Bi Y.W. Sun W.Y. Prostaglandin E1 reduces apoptosis and improves the homing of mesenchymal stem cells in pulmonary arterial hypertension by regulating hypoxia-inducible factor 1 alpha. Stem Cell Res. Ther. 2022 13 1 316 10.1186/s13287‑022‑03011‑x 35842683
    [Google Scholar]
  228. Pavoine C. Pecker F. Sphingomyelinases: Their regulation and roles in cardiovascular pathophysiology. Cardiovasc. Res. 2009 82 2 175 183 10.1093/cvr/cvp030 19176603
    [Google Scholar]
  229. Healy-Stoffel M. Levant B. N-3 (omega-3) fatty acids: Effects on brain dopamine systems and potential role in the etiology and treatment of neuropsychiatric disorders. CNS Neurol. Disord. Drug Targets 2018 17 3 216 232 10.2174/1871527317666180412153612 29651972
    [Google Scholar]
/content/journals/cn/10.2174/011570159X389784250715064745
Loading
Lipid Metabolism in Cerebral Ischemia: From Pathogenesis to Therapy
Bentham Science Publishers ; https://doi.org/10.2174/011570159X389784250715064745
/content/journals/cn/10.2174/011570159X389784250715064745
/content/journals/cn/10.2174/011570159X389784250715064745
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: Lipid metabolism ; cerebral ischemia ; therapeutic targets ; neuroinflammation ; specialized pro-resolving mediators (SPMs)

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test