Skip to content
2000
image of Drug Design for Cerebral Ischemia: A Molecular Perspective Review

Abstract

Ischemic stroke occurs when reduced or blocked blood flow prevents oxygen and nutrients from reaching brain tissue, resulting in neurological deficits. It is a leading cause of disability and death worldwide, with varying degrees of brain injury, from tissue damage to neuronal death and functional impairments. While restoring blood flow is necessary, it can worsen damage through oxidative stress, pro-inflammatory cytokines, apoptosis, blood-brain barrier disruption, cerebral edema, and hemorrhagic transformation. Neuroprotection plays a crucial role in reducing ischemic damage, with therapies targeting antioxidant, anti-inflammatory, and anti-ferroptotic pathways being essential. Current treatments for ischemia remain insufficient, and there is a lack of comprehensive reviews on drug candidates targeting this condition. This review aims to address this gap by evaluating 271 potential drug candidates for cerebral ischemia. It presents an in-depth analysis of compounds with core structures such as triazole, piperazine, pyrrole, amide, pyridine, and oxadiazole, along with functional groups like hydroxyl, halogen, and alkyl groups. These compounds exhibit promising neuroprotective, antioxidant, anti-ferroptotic, and anti-inflammatory effects. The encouraging findings highlight the need for further research and optimization to develop more effective therapeutic agents, reduce mortality, and prevent permanent disabilities associated with ischemic brain injuries.

Loading

Article metrics loading...

/content/journals/cnsnddt/10.2174/0118715273407230250916154803
2025-10-10
2025-11-25
Loading full text...

Full text loading...

References

  1. Zhang Q. Jia M. Wang Y. Wang Q. Wu J. Cell Death Mechanisms in Cerebral Ischemia–Reperfusion Injury. Neurochem. Res. 2022 47 12 3525 3542 10.1007/s11064‑022‑03697‑8 35976487
    [Google Scholar]
  2. Kidd PM Integrated brain restoration after ischemic stroke-medical management, risk factors, nutrients, and other interventions for managing inflammation and enhancing brain plasticity. Altern Med Rev 2009 14 1 14 35 19364191
    [Google Scholar]
  3. Zhao Y. Zhang X. Chen X. Wei Y. Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review). Int. J. Mol. Med. 2021 49 2 15 10.3892/ijmm.2021.5070 34878154
    [Google Scholar]
  4. Chen R. Zhang X. Gu L. New insight into neutrophils: A potential therapeutic target for cerebral ischemia. Front. Immunol. 2021 12 692061 10.3389/fimmu.2021.692061
    [Google Scholar]
  5. Lin L. Wang X. Yu Z. Ischemia-reperfusion Injury in the Brain: Mechanisms and Potential Therapeutic Strategies. Biochem. Pharmacol. (Los Angel.) 2016 5 4 213 10.4172/2167‑0501.1000213 29888120
    [Google Scholar]
  6. Wu L. Xiong X. Wu X. Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury. Front. Mol. Neurosci. 2020 13 28 10.3389/fnmol.2020.00028 32194375
    [Google Scholar]
  7. Allen C.L. Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int. J. Stroke 2009 4 6 461 470 10.1111/j.1747‑4949.2009.00387.x 19930058
    [Google Scholar]
  8. Orellana-Urzúa S. Rojas I. Líbano L. Rodrigo R. Pathophysiology of ischemic stroke: Role of oxidative stress. Curr. Pharm. Des. 2020 26 34 4246 4260 10.2174/1381612826666200708133912 32640953
    [Google Scholar]
  9. Zhu X. He L. Gao W. Zhao Z. Neuroprotective investigation of tanshinone in the cerebral infarction model in the Keap1-Nrf2/ARE pathway. Cell Cycle 2023 22 4 390 402 10.1080/15384101.2022.2119687 36066030
    [Google Scholar]
  10. Wang L. Zhang X. Xiong X. Nrf2 regulates oxidative stress and its role in cerebral ischemic stroke. Antioxidants 2022 11 12 2377 10.3390/antiox11122377
    [Google Scholar]
  11. Li X. Ye F. Li L. Chang W. Wu X. Chen J. The role of HO-1 in protection against lead-induced neurotoxicity. Neurotoxicology 2016 52 1 11 10.1016/j.neuro.2015.10.015 26542248
    [Google Scholar]
  12. Hu X. Bao Y. Li M. Zhang W. Chen C. The role of ferroptosis and its mechanism in ischemic stroke. Exp. Neurol. 2024 372 114630 10.1016/j.expneurol.2023.114630 38056585
    [Google Scholar]
  13. Li Y. Wu C. Yang R. Application and development of cell membrane functionalized biomimetic nanoparticles in the treatment of acute ischemic stroke. Int. J. Molecul. Sci. 2024 25 15 8539 10.3390/ijms25158539
    [Google Scholar]
  14. Mosconi M.G. Paciaroni M. Treatments in ischemic stroke: Current and future. Eur. Neurol. 2022 85 5 349 366 10.1159/000525822 35917794
    [Google Scholar]
  15. Carrillo Navarrete K.A. Chapa González C. Hemiplegia in acute ischemic stroke: A comprehensive review of case studies and the role of intravenous thrombolysis and mechanical thrombectomy. Ibrain 2024 10 1 59 68 10.1002/ibra.12146 38682021
    [Google Scholar]
  16. Wang X. Fang Y. Huang Q. An updated review of autophagy in ischemic stroke: From mechanisms to therapies. Exp. Neurol. 2021 340 113684 10.1016/j.expneurol.2021.113684 33676918
    [Google Scholar]
  17. Jurcau A. Ardelean I.A. Molecular pathophysiological mechanisms of ischemia/reperfusion injuries after recanalization therapy for acute ischemic stroke. J. Integr. Neurosci. 2021 20 3 727 744 10.31083/j.jin2003078 34645107
    [Google Scholar]
  18. Lin W. Zhao X.Y. Cheng J. Signaling pathways in brain ischemia: Mechanisms and therapeutic implications. Pharmacol. Ther. 2023 251 108541 10.1016/j.pharmthera.2023.108541 37783348
    [Google Scholar]
  19. Villa-González M. Martín-López G. Pérez-Álvarez M.J. Dysregulation of mTOR signaling after brain ischemia. Int. J. Mol. Sci. 2022 23 5 2814 10.3390/ijms23052814 35269956
    [Google Scholar]
  20. Marco-Contelles J. Zhang Y. From seeds of Apium graveolens Linn. to a cerebral ischemia medicine: The long journey of 3-n-Butylphthalide. J. Med. Chem. 2020 63 21 12485 12510 10.1021/acs.jmedchem.0c00887 32672958
    [Google Scholar]
  21. Zhou Q. Han C. Xia Y. Efficacy and safety of 3‐n‐butylphthalide for the treatment of cognitive impairment: A systematic review and meta‐analysis. CNS Neurosci. Ther. 2022 28 11 1706 1717 10.1111/cns.13952 36047338
    [Google Scholar]
  22. Bailly C. Hecquet P.E. Kouach M. Thuru X. Goossens J.F. Chemical reactivity and uses of 1-phenyl-3-methyl-5-pyrazolone (PMP), also known as edaravone. Bioorg. Med. Chem. 2020 28 10 115463 10.1016/j.bmc.2020.115463 32241621
    [Google Scholar]
  23. Lin S. Rhodes P.G. Lei M. Zhang F. Cai Z. α-Phenyl-n-tert-butyl-nitrone attenuates hypoxic–ischemic white matter injury in the neonatal rat brain. Brain Res. 2004 1007 1-2 132 141 10.1016/j.brainres.2004.01.074 15064144
    [Google Scholar]
  24. Zhou X. Zhu Z. Kuang S. Tetramethylpyrazine Nitrone (TBN) reduces amyloid β deposition in alzheimer’s disease models by modulating app expression, BACE1 activity, and autophagy pathways. Pharmaceuticals 2024 17 8 1005 10.3390/ph17081005 39204110
    [Google Scholar]
  25. Lao Y. Huang P. Chen J. Discovery of 1,2,4-triazole derivatives as novel neuroprotectants against cerebral ischemic injury by activating antioxidant response nlm. Bioorg. Chem. 2022 128 106096 10.1016/j.bioorg.2022.106096 35985158
    [Google Scholar]
  26. Wang Y. Su R. Chen J. Synthesis of 1,3,5-triphenyl-1,2,4-triazole derivatives and their neuroprotection by anti-oxidative stress and anti-inflammation and protecting BBB. Eur. J. Med. Chem. 2023 260 115742 10.1016/j.ejmech.2023.115742 37651874
    [Google Scholar]
  27. Liu X. Luo J. Chen J. The neuroprotection of 1,2,4‐triazole derivative by inhibiting inflammation and protecting BBB integrity in acute ischemic stroke. CNS Neurosci. Ther. 2024 30 11 e70113 10.1111/cns.70113 39500736
    [Google Scholar]
  28. Lao Y. Wang Y. Chen J. Synthesis and biological evaluation of 1,2,4-triazole derivatives as potential Nrf2 activators for the treatment of cerebral ischemic injury. Eur. J. Med. Chem. 2022 236 114315 10.1016/j.ejmech.2022.114315 35390713
    [Google Scholar]
  29. Lu Y. Lin H. Xu Y. Discovery of orally bioavailable phenyltetrazolium derivatives for the acute treatment and the secondary prevention of ischemic stroke. Eur. J. Med. Chem. 2024 275 116542 10.1016/j.ejmech.2024.116542 38875807
    [Google Scholar]
  30. Yu Q. Li Y. Luo Z. Novel 1,3,4-oxadiazole hybrids of 3-n-butylphthalide derivatives as potential anti-ischemic stroke agents. Bioorg. Chem. 2024 143 107034 10.1016/j.bioorg.2023.107034 38118299
    [Google Scholar]
  31. Shi J. Wang Y. Chen J. Synthesis and biological evaluation of 1,2,4-oxadiazole core derivatives as potential neuroprotectants against acute ischemic stroke. Neurochem. Int. 2021 148 105103 10.1016/j.neuint.2021.105103 34147514
    [Google Scholar]
  32. Cairang N. Wu Y. Zhi S. 5-(3-(N-(Carboxymethyl)-naphthalene-2-sulfonamido)phenyl)-1-ethyl-1H-pyrrole-2-car-boxylic acid as a Keap1–Nrf2 inhibitor for cerebral ischemia/reperfusion injury treatment. RSC Advances 2025 15 2 1052 1059 10.1039/D4RA06512C 39807188
    [Google Scholar]
  33. Tang J. Tie X. Zhi S. Discovery of novel 5-phenyl-1H-pyrrole-2-carboxylic acids as Keap1-Nrf2 inhibitors for acute lung injury treatment. Bioorg. Chem. 2024 153 107741 10.1016/j.bioorg.2024.107741 39232343
    [Google Scholar]
  34. Borozdenko D.A. Ezdoglian A.A. Shmigol T.A. A novel phenylpyrrolidine derivative: Synthesis and effect on cognitive functions in rats with experimental ishemic stroke. Molecules 2021 26 20 6124 10.3390/molecules26206124 34684709
    [Google Scholar]
  35. Li Y. He J. Luo B. Discovery of novel hybrids of edaravone and 6‐phenyl‐4,5‐dihydropyridazin‐3(2H)‐one with antiplatelet aggregation and neuroprotection for ischemic stroke treatment. Chem. Biodivers. 2024 21 5 e202400110 10.1002/cbdv.202400110 38424689
    [Google Scholar]
  36. Li X. Wang X. Miao L. Guo Y. Yuan R. Tian H. Design, synthesis, and neuroprotective effects of novel hybrid compounds containing edaravone analogue and 3-n-butylphthalide ring-opened derivatives. Biochem. Biophys. Res. Commun. 2021 556 99 105 10.1016/j.bbrc.2021.03.171 33839420
    [Google Scholar]
  37. Tang M.L. Wen Z.H. Wang J.H. Discovery of pyridone-substituted triazolopyrimidine dual A2A/A1 AR antagonists for the treatment of ischemic stroke. ACS Med. Chem. Lett. 2022 13 3 436 442 10.1021/acsmedchemlett.1c00599 35295085
    [Google Scholar]
  38. Hu L. Feng H. Zhang H. Development of novel N -hydroxypyridone derivatives as potential anti-ischemic stroke agents. J. Med. Chem. 2020 63 3 1051 1067 10.1021/acs.jmedchem.9b01338 31910018
    [Google Scholar]
  39. Zhu P. Wu Y. Du Z. Identification of 3-methyl-1-(3-methylpyridin-2-yl)-1H-pyrazol-5-ol as promising neuroprotective agent. Bioorg. Med. Chem. Lett. 2024 114 129983 10.1016/j.bmcl.2024.129983 39395634
    [Google Scholar]
  40. Zhong Y. Gao Y. Xu Y. Qi C. Wu B. Synthesis of Novel aryloxyethylamine derivatives and evaluation of their in Vitro and in vivo Neuroprotective Activities. Chem. Biodivers. 2020 17 9 e2000431 10.1002/cbdv.202000431 32583520
    [Google Scholar]
  41. Jia Y. Xiao H. Wang X. Design, synthesis, and evaluation of n-butylphthalide and ligustrazine hybrids as potent neuroprotective agents for the treatment of ischemic stroke in vitro and in vivo. Bioorg. Chem. 2024 142 106961 10.1016/j.bioorg.2023.106961 37956636
    [Google Scholar]
  42. Gao M. Ma S. Xu T. The design and synthesis of benzylpiperazine-based edaravone derivatives and their neuroprotective activities. J. Chem. Res. 2022 46 6 1 8 10.1177/17475198221116827
    [Google Scholar]
  43. Manzoor S. Almarghalani D.A. James A.W. Synthesis and pharmacological evaluation of novel triazole-pyrimidine hybrids as potential neuroprotective and anti-neuroinflammatory agents. Pharm. Res. 2023 40 1 167 185 10.1007/s11095‑022‑03429‑1 36376607
    [Google Scholar]
  44. Wang H. Cui E. Li J. Design and synthesis of novel indole and indazole-piperazine pyrimidine derivatives with anti-inflammatory and neuroprotective activities for ischemic stroke treatment. Eur. J. Med. Chem. 2022 241 114597 10.1016/j.ejmech.2022.114597 35931005
    [Google Scholar]
  45. Xiong L. Wu H. Zhong T. Design, synthesis and evaluation of novel 1,4-disubstituted piperazine-2,5-dione derivatives as antioxidants against H2O2-induced oxidative injury via the IL-6/Nrf2 loop pathway. Antioxidants 2022 11 10 2014 10.3390/antiox11102014 36290737
    [Google Scholar]
  46. Yang W. Liu X. Song C. Structure-activity relationship studies of phenothiazine derivatives as a new class of ferroptosis inhibitors together with the therapeutic effect in an ischemic stroke model. Eur. J. Med. Chem. 2021 209 112842 10.1016/j.ejmech.2020.112842 33065375
    [Google Scholar]
  47. Zeng Q. Zhang Z. Cai Z. Synthesis and neuroprotective evaluation of substituted indanone/benzofuranone and piperidine hybrids. ACS Chem. Neurosci. 2024 15 10 2042 2057 10.1021/acschemneuro.4c00054 38656184
    [Google Scholar]
  48. Yu Q. Luo B. Luo Z. Synthesis of novel 3‐butylphthalide derivatives containing isopentenylphenol moiety as potential antiplatelet agents for the treatment of ischemic stroke. Chem. Biodivers. 2023 20 1 e202201002 10.1002/cbdv.202201002 36424354
    [Google Scholar]
  49. Ji D. Jin C. Tao M. Design, synthesis, and biological evaluation of novel iNOS inhibitors as potent neuroprotective agents for ischemic stroke. Eur. J. Med. Chem. 2024 280 116907 10.1016/j.ejmech.2024.116907 39368264
    [Google Scholar]
  50. Lin G. Xu Q. Li J. Design, synthesis, and biological evaluation of Pierardine derivatives as novel brain-penetrant and In Vivo potent NMDAR-GluN2B antagonists for ischemic stroke treatment. J. Med. Chem. 2024 67 5 3358 3384 10.1021/acs.jmedchem.3c01524 38413367
    [Google Scholar]
  51. Fang X. Ma Q. Zhang K.X. Synthesis of phthalide derivatives and evaluation on their antiplatelet aggregation and antioxidant activities. J. Asian Nat. Prod. Res. 2020 22 12 1176 1187 10.1080/10286020.2019.1681982 31755304
    [Google Scholar]
  52. Chichai A.S. Popova T.N. Kryl’skii E.D. Oleinik S.A. Razuvaev G.A. Indole-3-carbinol mitigates oxidative stress and inhibits inflammation in rat cerebral ischemia/reperfusion model. Biochimie 2023 213 1 11 10.1016/j.biochi.2023.04.018 37120006
    [Google Scholar]
  53. Xie Y. Zou X. Han J. Indole-3-propionic acid alleviates ischemic brain injury in a mouse middle cerebral artery occlusion model. Exp. Neurol. 2022 353 114081 10.1016/j.expneurol.2022.114081 35405119
    [Google Scholar]
  54. Luo X. Zeng H. Fang C. Zhang B.H. N-acetylserotonin derivative exerts a neuroprotective effect by inhibiting the NLRP3 Inflammasome and activating the PI3K/Akt/Nrf2 pathway in the model of hypoxic-ischemic brain damage. Neurochem. Res. 2021 46 2 337 348 10.1007/s11064‑020‑03169‑x 33222058
    [Google Scholar]
  55. Wu G. Li B. Wei X. Design, synthesis and biological evaluation of N-salicyloyl tryptamine derivatives as multifunctional neuroprotectants for the treatment of ischemic stroke. Eur. J. Med. Chem. 2024 278 116795 10.1016/j.ejmech.2024.116795 39216381
    [Google Scholar]
  56. Kong L. Ma Y. Wang Z. Inhibition of hypoxia inducible factor 1 by YC-1 attenuates tissue plasminogen activator induced hemorrhagic transformation by suppressing HMGB1/TLR4/NF-κB mediated neutrophil infiltration in thromboembolic stroke rats. Int. Immunopharmacol. 2021 94 107507 10.1016/j.intimp.2021.107507 33657523
    [Google Scholar]
  57. Yu K.H. Hung H.Y. Synthetic strategy and structure–activity relationship (SAR) studies of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1, Lificiguat): a review. RSC Advances 2021 12 1 251 264 10.1039/D1RA08120A 35424505
    [Google Scholar]
  58. Cao R. Du F. Cui Y. Synthesis and biological evaluations of 8-biaryl-2,2-dimethylbenzopyranamide derivatives against Alzheimer’s disease and ischemic stroke. Bioorg. Chem. 2024 143 107064 10.1016/j.bioorg.2023.107064 38150937
    [Google Scholar]
  59. Wang S. Chen Y. Xia C. Synthesis and evaluation of glycosylated quercetin to enhance neuroprotective effects on cerebral ischemia-reperfusion. Bioorg. Med. Chem. 2022 73 117008 10.1016/j.bmc.2022.117008 36126445
    [Google Scholar]
  60. Wan B.W. Liu W. Xiao Y. Discovery of novel benzo[b][1,4]oxazine derivatives as ferroptosis inhibitors. Bioorg. Chem. 2025 156 108201 10.1016/j.bioorg.2025.108201 39864374
    [Google Scholar]
  61. Shen M. Zheng Y. Li G. Dual antioxidant DH-217 mitigated cerebral ischemia–reperfusion injury by targeting IKKβ/Nrf2/HO-1 signal axis. Neurochem. Res. 2023 48 2 579 590 10.1007/s11064‑022‑03783‑x 36243818
    [Google Scholar]
  62. He W. Wang J. Jin Q. Design, green synthesis, antioxidant activity screening, and evaluation of protective effect on cerebral ischemia reperfusion injury of novel monoenone monocarbonyl curcumin analogs. Bioorg. Chem. 2021 114 105080 10.1016/j.bioorg.2021.105080 34225164
    [Google Scholar]
  63. Jiao F. Song Y. Wang X. Zhang T. Synthesis of chalcone derivatives as COX-2 Inhibitory activity for ischemic stroke treatment. Chem. Nat. Compd. 2024 60 1 13 16 10.1007/s10600‑024‑04241‑6
    [Google Scholar]
  64. Wu J. Yin W. Zhang Y. Design and synthesis of the ring-opened derivative of 3-n-butylphthalide-ferulic acid-glucose trihybrids as potential anti-ischemic agents. Chin. Chem. Lett. 2020 31 7 1881 1886 10.1016/j.cclet.2020.02.031
    [Google Scholar]
  65. Chen L.Y. Yang C.Z. Xu Y. Qi C.Y. Zhong Y. Wu B. Synthesis, crystal structure, and biological evaluation of (E)-1-(4-(4-Bromobenzyl)Piperazin-1-Yl)-3-(4-Chlorophenyl)Prop-2-En-1-One. J. Struct. Chem. 2021 62 3 481 490 10.1134/S002247662103015X
    [Google Scholar]
  66. Evans R. Bolduc P.N. Pfaffenbach M. The discovery of] 7-Isopropoxy-2-(1-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)-N-(6-methylpyrazolo[1,5-a]pyrimidin-3-yl)imidazo[1,2-a]pyrimidine-6-carboxamide (BIO-7488), a potent, selective, and CNS-penetrant IRAK4 inhibitor for the treatment of ischemic stroke. J. Med. Chem. 2024 67 6 4676 4690 10.1021/acs.jmedchem.3c02226 38467640
    [Google Scholar]
  67. Li J.Y. Peng X.Y. Huang Y.L. Design, synthesis, and neuroprotective effects of novel cinnamamide-piperidine and piperazine derivatives. Pharmaceutical Fronts 2023 5 3 e132 e140 10.1055/s‑0043‑1774288
    [Google Scholar]
  68. Toti K.S. Verma R. McGonnigle M.J. Structure–activity relationship and neuroprotective activity of 1,5-Dihydro-2H-naphtho [1,2-b][1,4]diazepine-2,4(3H)-diones as P2X4 receptor antagonists. J. Med. Chem. 2022 65 20 13967 13987 10.1021/acs.jmedchem.2c01197 36150180
    [Google Scholar]
  69. Chen Y.L. Chen Y.C. Xiong L.A. Discovery of phenylcarbamoyl xanthone derivatives as potent neuroprotective agents for treating ischemic stroke. Eur. J. Med. Chem. 2023 251 115251 10.1016/j.ejmech.2023.115251 36921528
    [Google Scholar]
  70. Chamorro B. Diez-Iriepa D. Merás-Sáiz B. Synthesis, antioxidant properties and neuroprotection of α-phenyl-tert-butylnitrone derived HomoBisNitrones in in vitro and in vivo ischemia models. Sci. Rep. 2020 10 1 14150 10.1038/s41598‑020‑70690‑y
    [Google Scholar]
  71. Fei Y. Li T. Wu R. Se-(Methyl)-selenocysteine ameliorates blood-brain barrier disruption of focal cerebral ischemia mice via ferroptosis inhibition and tight junction upregulation in an Akt/GSK3β-dependent manner. Psychopharmacology (Berl.) 2024 241 2 379 399 10.1007/s00213‑023‑06495‑4 38019326
    [Google Scholar]
  72. Xu L. Gao Y. Hu M. Edaravone dexborneol protects cerebral ischemia reperfusion injury through activating Nrf2/HO‐1 signaling pathway in mice. Fundam. Clin. Pharmacol. 2022 36 5 790 800 10.1111/fcp.12782 35470467
    [Google Scholar]
  73. Lochhead J.J. Ronaldson P.T. Davis T.P. The role of oxidative stress in blood–brain barrier disruption during ischemic stroke: antioxidants in clinical trials. Biochem. Pharmacol. 2024 228 116186 10.1016/j.bcp.2024.116186
    [Google Scholar]
  74. Ramli F.F. Singh N. Emir U.E. Effects of ebselen addition on emotional processing and brain neurochemistry in depressed patients unresponsive to antidepressant medication. Transl. Psychiatry 2024 14 1 200 10.1038/s41398‑024‑02899‑8 38714646
    [Google Scholar]
  75. Wardlaw J.M. Woodhouse L.J. Mhlanga I.I. Isosorbide mononitrate and cilostazol treatment in patients with symptomatic cerebral small vessel disease. JAMA Neurol. 2023 80 7 682 10.1001/jamaneurol.2023.1526
    [Google Scholar]
  76. Ahmed SR Khalil MF Ismaiel M Cilostazole versus clopidogrel in acute large-vessel moderate and moderate-to-severe ischemic stroke: a randomized controlled trial. Neurol. Sci. 2025 46 3973 3986 10.1007/s10072‑025‑08107‑9
    [Google Scholar]
  77. Baang HY Reynolds AS Dangayach NS Treatment effect of early intravenous milrinone for cerebral vasospasm or delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neurocrit. Care 2025 43 19 26 10.1007/s12028‑025‑02260‑x 40329063
    [Google Scholar]
  78. Lee J.S. Kang H.G. Ahn S.H. Nelonemdaz and patients with acute ischemic stroke and mechanical reperfusion. JAMA Netw. Open 2025 8 1 e2456535 10.1001/jamanetworkopen.2024.56535 39874036
    [Google Scholar]
  79. Tymianski M. Hill M.D. Goyal M. Safety and efficacy of nerinetide in patients with acute ischaemic stroke enrolled in the early window: A post-hoc meta-analysis of individual patient data from three randomised trials. Lancet Neurol. 2025 24 3 208 217 10.1016/S1474‑4422(24)00515‑5 39956129
    [Google Scholar]
  80. Agarwal A. Vishnu V.Y. Sharma J. Citicoline in acute ischemic stroke: A randomized controlled trial. PLoS One 2022 17 269224 10.1371/journal.pone.0269224
    [Google Scholar]
  81. Zhang X. Zhong W. Xue R. Argatroban in patients with acute ischemic stroke with early neurological deterioration. JAMA Neurol. 2024 81 2 118 125 10.1001/jamaneurol.2023.5093 38190136
    [Google Scholar]
  82. Fu Y. Wang A. Tang R. Sublingual edaravone dexborneol for the treatment of acute ischemic stroke. JAMA Neurol. 2024 81 4 319 326 10.1001/jamaneurol.2023.5716 38372981
    [Google Scholar]
  83. Dong Y. Jiang K. Li Z. Tongxinluo and functional outcomes among patients with acute ischemic stroke. JAMA Netw. Open 2024 7 9 e2433463 10.1001/jamanetworkopen.2024.33463 39325453
    [Google Scholar]
/content/journals/cnsnddt/10.2174/0118715273407230250916154803
Loading
/content/journals/cnsnddt/10.2174/0118715273407230250916154803
Loading

Data & Media loading...

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