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image of Therapeutic Values of General Anesthetics: From Developmental Neurotoxicity to Neurotherapeutic Agents

Abstract

The development of the central nervous system is characterized by precisely orchestrated, dynamic processes that commence at the embryonic stage and continue throughout postnatal life. Maintaining the balance between excitation/inhibition (E/I) in cortical neuronal circuits is crucial for normal brain function. General anesthetics (GAs) powerfully modulate neuronal activity by enhancing inhibition and/or inhibiting excitability, resulting in temporary loss of consciousness. Therefore, these agents can also induce aberrant neuroplasticity contributing to neurological dysfunction and abnormal behavioural phenotypes, particularly in the developing brain. While this impaired plasticity poses a risk, it also creates an opportunity to treat diseases characterised by abnormal neuroplasticity as core pathologies, such as neuropsychiatric disorders (NPDs). Over recent decades, intense investigations have revealed the neuroprotective and psychotherapeutic potential of GAs in treating neurological injuries and NPDs. Although promising, significant challenges remain, including optimizing dosages, administration duration, and intervals for non-anesthetic uses while minimizing adverse effects. Additionally, the molecular mechanisms underlying the dual roles of GAs - as neurotoxic agents and neurotherapeutic tools - require further elucidation. This review explores developmental neuroplasticity during critical periods, the mechanisms of GAs' action on neural circuits, and the current understanding of their neurotoxic and neuroprotective effects based on alterations in neuroplasticity. Furthermore, we highlight the therapeutic potential of GAs for neurological disorders with impaired neuroplasticity as the core pathological mechanism and propose directions for future research to unlock their full clinical utility.

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2025-11-29
2025-12-15
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References

  1. Robinson D.H. Toledo A.H. Historical development of modern anesthesia. J. Invest. Surg. 2012 25 3 141 149 10.3109/08941939.2012.690328 22583009
    [Google Scholar]
  2. Delgado-Herrera L. Ostroff R.D. Rogers S.A. Sevoflurance: Approaching the ideal inhalational anesthetic. A pharmacologic, pharmacoeconomic, and clinical review. CNS Drug Rev. 2001 7 1 48 120 10.1111/j.1527‑3458.2001.tb00190.x 11420572
    [Google Scholar]
  3. Rudolph U. Antkowiak B. Molecular and neuronal substrates for general anaesthetics. Nat. Rev. Neurosci. 2004 5 9 709 720 10.1038/nrn1496 15322529
    [Google Scholar]
  4. Moody O.A. Zhang E.R. Vincent K.F. Kato R. Melonakos E.D. Nehs C.J. Solt K. The neural circuits underlying general anesthesia and sleep. Anesth. Analg. 2021 132 5 1254 1264 10.1213/ANE.0000000000005361 33857967
    [Google Scholar]
  5. Campagna J.A. Miller K.W. Forman S.A. Mechanisms of actions of inhaled anesthetics. N. Engl. J. Med. 2003 348 21 2110 2124 10.1056/NEJMra021261 12761368
    [Google Scholar]
  6. Wu Z. Yu W. Song Y. Zhao P. General anaesthesia, the developing brain, and cerebral white matter alterations: A narrative review. Br. J. Anaesth. 2023 131 6 1022 1029 10.1016/j.bja.2023.09.008 37833128
    [Google Scholar]
  7. Ing C. Warner D.O. Sun L.S. Flick R.P. Davidson A.J. Vutskits L. McCann M.E. O’Leary J. Bellinger D.C. Rauh V. Orser B.A. Suresh S. Andropoulos D.B. Anesthesia and developing brains: unanswered questions and proposed paths forward. Anesthesiology 2022 136 3 500 512 10.1097/ALN.0000000000004116 35015802
    [Google Scholar]
  8. Vutskits L. Davidson A. Clinical investigations on anesthesia-induced developmental neurotoxicity: The knowns, the unknowns and future prospects. Baillieres. Best Pract. Res. Clin. Anaesthesiol. 2023 37 1 40 51 10.1016/j.bpa.2023.02.004 37295853
    [Google Scholar]
  9. Salaün J.P. Chagnot A. Cachia A. Poirel N. Datin-Dorrière V. Dujarrier C. Lemarchand E. Rolland M. Delalande L. Gressens P. Guillois B. Houdé O. Levard D. Gakuba C. Moyon M. Naveau M. Orliac F. Orliaguet G. Hanouz J.L. Agin V. Borst G. Vivien D. Consequences of general anesthesia in infancy on behavior and brain structure. Anesth. Analg. 2023 136 2 240 250 10.1213/ANE.0000000000006233 36638508
    [Google Scholar]
  10. Colletti G. Di Bartolomeo M. Negrello S. Geronemus R.G. Cohen B. Chiarini L. Anesi A. Feminò R. Mariotti I. Levitin G.M. Rozell-Shannon L. Nocini R. Multiple General anesthesia in children: A systematic review of its effect on neurodevelopment. J. Pers. Med. 2023 13 5 867 10.3390/jpm13050867 37241037
    [Google Scholar]
  11. Ing C. Bellinger D.C. Long-term cognitive and behavioral outcomes following early exposure to general anesthetics. Curr. Opin. Anaesthesiol. 2022 35 4 442 447 10.1097/ACO.0000000000001155 35788121
    [Google Scholar]
  12. Andropoulos D.B. Greene M.F. Anesthesia and developing brains — Implications of the FDA warning. N. Engl. J. Med. 2017 376 10 905 907 10.1056/NEJMp1700196 28177852
    [Google Scholar]
  13. Sohal V.S. Rubenstein J.L.R. Excitation-inhibition balance as a framework for investigating mechanisms in neuropsychiatric disorders. Mol. Psychiatry 2019 24 9 1248 1257 10.1038/s41380‑019‑0426‑0 31089192
    [Google Scholar]
  14. Nelson S.B. Valakh V. Excitatory/inhibitory balance and circuit homeostasis in autism spectrum disorders. Neuron 2015 87 4 684 698 10.1016/j.neuron.2015.07.033 26291155
    [Google Scholar]
  15. Noctor S.C. Martínez-Cerdeño V. Kriegstein A.R. Distinct behaviors of neural stem and progenitor cells underlie cortical neurogenesis. J. Comp. Neurol. 2008 508 1 28 44 10.1002/cne.21669 18288691
    [Google Scholar]
  16. Noctor S.C. Martínez-Cerdeño V. Ivic L. Kriegstein A.R. Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat. Neurosci. 2004 7 2 136 144 10.1038/nn1172 14703572
    [Google Scholar]
  17. Reemst K. Noctor S.C. Lucassen P.J. Hol E.M. The Indispensable Roles of Microglia and Astrocytes during Brain Development. Front. Hum. Neurosci. 2016 10 566 10.3389/fnhum.2016.00566 27877121
    [Google Scholar]
  18. Macht V.A. Neuro-immune interactions across development: A look at glutamate in the prefrontal cortex. Neurosci. Biobehav. Rev. 2016 71 267 280 10.1016/j.neubiorev.2016.08.039 27593444
    [Google Scholar]
  19. Bandeira F. Lent R. Herculano-Houzel S. Changing numbers of neuronal and non-neuronal cells underlie postnatal brain growth in the rat. Proc. Natl. Acad. Sci. USA 2009 106 33 14108 14113 10.1073/pnas.0804650106 19666520
    [Google Scholar]
  20. Kim W.R. Sun W. Programmed cell death during postnatal development of the rodent nervous system. Dev. Growth Differ. 2011 53 2 225 235 10.1111/j.1440‑169X.2010.01226.x 21338348
    [Google Scholar]
  21. Chakraborty R. Vijay Kumar M.J. Clement J.P. Critical aspects of neurodevelopment. Neurobiol. Learn. Mem. 2021 180 107415 10.1016/j.nlm.2021.107415 33647449
    [Google Scholar]
  22. Meyer H.C. Lee F.S. Translating developmental neuroscience to understand risk for psychiatric disorders. Am. J. Psychiatry 2023 180 8 540 547 10.1176/appi.ajp.19010091 37525605
    [Google Scholar]
  23. Fuchs E. Flügge G. Adult neuroplasticity: More than 40 years of research. Neural Plast. 2014 2014 1 10 10.1155/2014/541870 24883212
    [Google Scholar]
  24. Innocenti G.M. Defining neuroplasticity. Handb. Clin. Neurol. 2022 184 3 18 10.1016/B978‑0‑12‑819410‑2.00001‑1 35034744
    [Google Scholar]
  25. Ismail F.Y. Fatemi A. Johnston M.V. Cerebral plasticity: Windows of opportunity in the developing brain. Eur. J. Paediatr. Neurol. 2017 21 1 23 48 10.1016/j.ejpn.2016.07.007 27567276
    [Google Scholar]
  26. Anderson V. Spencer-Smith M. Wood A. Do children really recover better? Neurobehavioural plasticity after early brain insult. Brain 2011 134 8 2197 2221 10.1093/brain/awr103 21784775
    [Google Scholar]
  27. Chaudhury S. Sharma V. Kumar V. Nag T.C. Wadhwa S. Activity-dependent synaptic plasticity modulates the critical phase of brain development. Brain Dev. 2016 38 4 355 363 10.1016/j.braindev.2015.10.008 26515724
    [Google Scholar]
  28. Johnston M.V. Clinical disorders of brain plasticity. Brain Dev. 2004 26 2 73 80 10.1016/S0387‑7604(03)00102‑5 15036425
    [Google Scholar]
  29. Südhof T.C. Towards an Understanding of Synapse Formation. Neuron 2018 100 2 276 293 10.1016/j.neuron.2018.09.040 30359597
    [Google Scholar]
  30. Allen N.J. Lyons D.A. Glia as architects of central nervous system formation and function. Science 2018 362 6411 181 185 10.1126/science.aat0473 30309945
    [Google Scholar]
  31. Duffy A.S. Eyo U.B. Microglia and astrocytes in postnatal neural circuit formation. Glia 2025 73 2 232 250 10.1002/glia.24650 39568399
    [Google Scholar]
  32. Mordelt A. de Witte L.D. Microglia-mediated synaptic pruning as a key deficit in neurodevelopmental disorders: Hype or hope? Curr. Opin. Neurobiol. 2023 79 102674 10.1016/j.conb.2022.102674 36657237
    [Google Scholar]
  33. Ben-Ari Y. Khazipov R. Leinekugel X. Caillard O. Gaiarsa J.L. GABAA, NMDA and AMPA receptors: A developmentally regulated ‘ménage à trois’. Trends Neurosci. 1997 20 11 523 529 10.1016/S0166‑2236(97)01147‑8 9364667
    [Google Scholar]
  34. McDonald J.W. Johnston M.V. Physiological and pathophysiological roles of excitatory amino acids during central nervous system development. Brain Res. Brain Res. Rev. 1990 15 1 41 70 10.1016/0165‑0173(90)90011‑C 2163714
    [Google Scholar]
  35. Wang D.D. Kriegstein A.R. Defining the role of GABA in cortical development. J. Physiol. 2009 587 9 1873 1879 10.1113/jphysiol.2008.167635 19153158
    [Google Scholar]
  36. Luján R. Shigemoto R. López-Bendito G. Glutamate and GABA receptor signalling in the developing brain. Neuroscience 2005 130 3 567 580 10.1016/j.neuroscience.2004.09.042 15590141
    [Google Scholar]
  37. Li S. Kumar T. P.; Joshee, S.; Kirschstein, T.; Subburaju, S.; Khalili, J.S.; Kloepper, J.; Du, C.; Elkhal, A.; Szabó, G.; Jain, R.K.; Köhling, R.; Vasudevan, A. Endothelial cell-derived GABA signaling modulates neuronal migration and postnatal behavior. Cell Res. 2018 28 2 221 248 10.1038/cr.2017.135 29086765
    [Google Scholar]
  38. Bajaj S. Bagley J.A. Sommer C. Vertesy A. Nagumo Wong S. Krenn V. Lévi-Strauss J. Knoblich J.A. Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration. EMBO J. 2021 40 23 e108714 10.15252/embj.2021108714 34661293
    [Google Scholar]
  39. De Jager J.E. Boesjes R. Roelandt G.H.J. Koliaki I. Sommer I.E.C. Schoevers R.A. Nuninga J.O. Shared effects of electroconvulsive shocks and ketamine on neuroplasticity: A systematic review of animal models of depression. Neurosci. Biobehav. Rev. 2024 164 105796 10.1016/j.neubiorev.2024.105796 38981574
    [Google Scholar]
  40. de Vos C.M.H. Mason N.L. Kuypers K.P.C. Psychedelics and neuroplasticity: A systematic review unraveling the biological underpinnings of psychedelics. Front. Psychiatry 2021 12 724606 10.3389/fpsyt.2021.724606 34566723
    [Google Scholar]
  41. Deng J. Lei C. Chen Y. Fang Z. Yang Q. Zhang H. Cai M. Shi L. Dong H. Xiong L. Neuroprotective gases – Fantasy or reality for clinical use? Prog. Neurobiol. 2014 115 210 245 10.1016/j.pneurobio.2014.01.001 24440817
    [Google Scholar]
  42. Franks N.P. Lieb W.R. Do general anaesthetics act by competitive binding to specific receptors? Nature 1984 310 5978 599 601 10.1038/310599a0 6462249
    [Google Scholar]
  43. Koblin D.D. Chortkoff B.S. Laster M.J. Eger E.I. Halsey M.J. Ionescu P. Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis. Anesth. Analg. 1994 79 6 1043 1048 10.1213/00000539‑199412000‑00004 7978424
    [Google Scholar]
  44. Hao X. Ou M. Zhang D. Zhao W. Yang Y. Liu J. Yang H. Zhu T. Li Y. Zhou C. The effects of general anesthetics on synaptic transmission. Curr. Neuropharmacol. 2020 18 10 936 965 10.2174/1570159X18666200227125854 32106800
    [Google Scholar]
  45. Platholi J. Hemmings H.C. Effects of general anesthetics on synaptic transmission and plasticity. Curr. Neuropharmacol. 2022 20 1 27 54 10.2174/1570159X19666210803105232 34344292
    [Google Scholar]
  46. Speigel I.A. Hemmings H.C. Relevance of cortical and hippocampal interneuron functional diversity to general anesthetic mechanisms: a narrative review. Front. Synaptic Neurosci. 2022 13 812905 10.3389/fnsyn.2021.812905 35153712
    [Google Scholar]
  47. Franks N.P. Lieb W.R. Molecular mechanisms of general anaesthesia. Nature 1982 300 5892 487 493 10.1038/300487a0 6755267
    [Google Scholar]
  48. Franks N.P. Lieb W.R. Molecular and cellular mechanisms of general anaesthesia. Nature 1994 367 6464 607 614 10.1038/367607a0 7509043
    [Google Scholar]
  49. Diao S. Ni J. Shi X. Liu P. Xia W. Mechanisms of action of general anesthetics. Front. Biosci. 2014 19 5 747 757 10.2741/4241 24389218
    [Google Scholar]
  50. Simon W. Hapfelmeier G. Kochs E. Zieglgänsberger W. Rammes G. Isoflurane blocks synaptic plasticity in the mouse hippocampus. Anesthesiology 2001 94 6 1058 1065 10.1097/00000542‑200106000‑00021 11465598
    [Google Scholar]
  51. Ren L. Hao X. Min S. Deng J. Chen Q. Chen H. Liu D. Anesthetics alleviate learning and memory impairment induced by electroconvulsive shock by regulation of NMDA receptor-mediated metaplasticity in depressive rats. Neurobiol. Learn. Mem. 2018 155 65 77 10.1016/j.nlm.2018.06.013 29953948
    [Google Scholar]
  52. Yu X. Zhang F. Shi J. Neonatal exposure to sevoflurane caused cognitive deficits by dysregulating SK2 channels and GluA2-lacking AMPA receptors in juvenile rat hippocampus. Neuropharmacology 2018 141 66 75 10.1016/j.neuropharm.2018.08.014 30142400
    [Google Scholar]
  53. Niu W. Duan Y. Kang Y. Cao X. Xue Q. Propofol improves learning and memory in post-traumatic stress disorder (PTSD) mice via recovering hippocampus synaptic plasticity. Life Sci. 2022 293 120349 10.1016/j.lfs.2022.120349 35065162
    [Google Scholar]
  54. Khodaei S. Wang D.S. Orser B.A. Reduced excitatory neurotransmission in the hippocampus after inflammation and sevoflurane anaesthesia. BJA Open 2023 6 100143 10.1016/j.bjao.2023.100143 37588178
    [Google Scholar]
  55. Jia D.W. Vogels T.P. Costa R.P. Developmental depression-to-facilitation shift controls excitation-inhibition balance. Commun. Biol. 2022 5 1 873 10.1038/s42003‑022‑03801‑2 36008708
    [Google Scholar]
  56. Zhang Z. Jiao Y.Y. Sun Q.Q. Developmental maturation of excitation and inhibition balance in principal neurons across four layers of somatosensory cortex. Neuroscience 2011 174 10 25 10.1016/j.neuroscience.2010.11.045 21115101
    [Google Scholar]
  57. Perica M.I. Calabro F.J. Larsen B. Foran W. Yushmanov V.E. Hetherington H. Tervo-Clemmens B. Moon C.H. Luna B. Development of frontal GABA and glutamate supports excitation/inhibition balance from adolescence into adulthood. Prog. Neurobiol. 2022 219 102370 10.1016/j.pneurobio.2022.102370 36309210
    [Google Scholar]
  58. Lopatina O.L. Malinovskaya N.A. Komleva Y.K. Gorina Y.V. Shuvaev A.N. Olovyannikova R.Y. Belozor O.S. Belova O.A. Higashida H. Salmina A.B. Excitation/inhibition imbalance and impaired neurogenesis in neurodevelopmental and neurodegenerative disorders. Rev. Neurosci. 2019 30 8 807 820 10.1515/revneuro‑2019‑0014 31152644
    [Google Scholar]
  59. Selten M. van Bokhoven H. Nadif Kasri N. Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders. F1000 Res. 2018 7 23 10.12688/f1000research.12155.1 29375819
    [Google Scholar]
  60. Lee E. Lee J. Kim E. Excitation/inhibition imbalance in animal models of autism spectrum disorders. Biol. Psychiatry 2017 81 10 838 847 10.1016/j.biopsych.2016.05.011 27450033
    [Google Scholar]
  61. Populin L.C. Anesthetics change the excitation/inhibition balance that governs sensory processing in the cat superior colliculus. J. Neurosci. 2005 25 25 5903 5914 10.1523/JNEUROSCI.1147‑05.2005 15976079
    [Google Scholar]
  62. Chen C. Li S. Zhou Y. Huang H. Lin J.T. Wu W.F. Qiu Y.K. Dong W. Wan J. Liu Q. Zheng H. Wu Y.Q. Zhou C.H. Neuronal excitation-inhibition imbalance in the basolateral amygdala is involved in propofol-mediated enhancement of fear memory. Commun. Biol. 2024 7 1 1408 10.1038/s42003‑024‑07105‑5 39472670
    [Google Scholar]
  63. Kasai M. Isa T. Effects of light isoflurane anesthesia on organization of direction and orientation selectivity in the superficial layer of the mouse superior colliculus. J. Neurosci. 2022 42 4 619 630 10.1523/JNEUROSCI.1196‑21.2021 34872926
    [Google Scholar]
  64. Fogaca M.V. Daher F. Picciotto M.R. Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: Biphasic recruitment of GABA function in antidepressant-like responses. Neuropsychopharmacology 2024 39390105
    [Google Scholar]
  65. Zhao T. Chen Y. Sun Z. Shi Z. Qin J. Lu J. Li C. Ma D. Zhou L. Song X. Prenatal sevoflurane exposure causes neuronal excitatory/inhibitory imbalance in the prefrontal cortex and neurofunctional abnormality in rats. Neurobiol. Dis. 2020 146 105121 10.1016/j.nbd.2020.105121 33007389
    [Google Scholar]
  66. Eizaga Rebollar R. García Palacios M.V. Morales Guerrero J. Torres Morera L.M. Neurotoxicity versus neuroprotection of anesthetics: Young children on the ropes? Paediatr. Drugs 2017 19 4 271 275 10.1007/s40272‑017‑0230‑8 28466422
    [Google Scholar]
  67. Yan Y. Logan S. Liu X. Chen B. Jiang C. Arzua T. Ramchandran R. Liu Q. Bai X. Integrated Excitatory/inhibitory imbalance and transcriptomic analysis reveals the association between dysregulated synaptic genes and anesthetic-induced cognitive dysfunction. Cells 2022 11 16 2497 10.3390/cells11162497 36010580
    [Google Scholar]
  68. Jevtovic-Todorovic V. General anesthetics and neurotoxicity. Anesthesiol. Clin. 2016 34 3 439 451 10.1016/j.anclin.2016.04.001 27521190
    [Google Scholar]
  69. Fong T.G. Davis D. Growdon M.E. Albuquerque A. Inouye S.K. The interface between delirium and dementia in elderly adults. Lancet Neurol. 2015 14 8 823 832 10.1016/S1474‑4422(15)00101‑5 26139023
    [Google Scholar]
  70. Devinney M.J. Mathew J.P. Berger M. Postoperative delirium and postoperative cognitive dysfunction. Anesthesiology 2018 129 3 389 391 10.1097/ALN.0000000000002338 29965817
    [Google Scholar]
  71. Jevtovic-Todorovic V. Absalom A.R. Blomgren K. Brambrink A. Crosby G. Culley D.J. Fiskum G. Giffard R.G. Herold K.F. Loepke A.W. Ma D. Orser B.A. Planel E. Slikker W. Soriano S.G. Stratmann G. Vutskits L. Xie Z. Hemmings H.C. Anaesthetic neurotoxicity and neuroplasticity: An expert group report and statement based on the BJA Salzburg Seminar. Br. J. Anaesth. 2013 111 2 143 151 10.1093/bja/aet177 23722106
    [Google Scholar]
  72. Ikonomidou C. Bosch F. Miksa M. Bittigau P. Vöckler J. Dikranian K. Tenkova T.I. Stefovska V. Turski L. Olney J.W. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999 283 5398 70 74 10.1126/science.283.5398.70 9872743
    [Google Scholar]
  73. Olney J.W. Ishimaru M.J. Bittigau P. Ikonomidou C. Ethanol-induced apoptotic neurodegeneration in the developing brain. Apoptosis 2000 5 6 515 521 10.1023/A:1009685428847 11303910
    [Google Scholar]
  74. Ikonomidou C. Bittigau P. Ishimaru M.J. Wozniak D.F. Koch C. Genz K. Price M.T. Stefovska V. Hörster F. Tenkova T. Dikranian K. Olney J.W. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 2000 287 5455 1056 1060 10.1126/science.287.5455.1056 10669420
    [Google Scholar]
  75. Jevtovic-Todorovic V. Hartman R.E. Izumi Y. Benshoff N.D. Dikranian K. Zorumski C.F. Olney J.W. Wozniak D.F. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J. Neurosci. 2003 23 3 876 882 10.1523/JNEUROSCI.23‑03‑00876.2003 12574416
    [Google Scholar]
  76. Head B.P. Patel H.H. Niesman I.R. Drummond J.C. Roth D.M. Patel P.M. Inhibition of p75 neurotrophin receptor attenuates isoflurane-mediated neuronal apoptosis in the neonatal central nervous system. Anesthesiology 2009 110 4 813 825 10.1097/ALN.0b013e31819b602b 19293698
    [Google Scholar]
  77. Satomoto M. Satoh Y. Terui K. Miyao H. Takishima K. Ito M. Imaki J. Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology 2009 110 3 628 637 10.1097/ALN.0b013e3181974fa2 19212262
    [Google Scholar]
  78. Slikker W. Zou X. Hotchkiss C.E. Divine R.L. Sadovova N. Twaddle N.C. Doerge D.R. Scallet A.C. Patterson T.A. Hanig J.P. Paule M.G. Wang C. Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol. Sci. 2007 98 1 145 158 10.1093/toxsci/kfm084 17426105
    [Google Scholar]
  79. Brambrink A.M. Evers A.S. Avidan M.S. Farber N.B. Smith D.J. Zhang X. Dissen G.A. Creeley C.E. Olney J.W. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology 2010 112 4 834 841 10.1097/ALN.0b013e3181d049cd 20234312
    [Google Scholar]
  80. Briner A. De Roo M. Dayer A. Muller D. Habre W. Vutskits L. Volatile anesthetics rapidly increase dendritic spine density in the rat medial prefrontal cortex during synaptogenesis. Anesthesiology 2010 112 3 546 556 10.1097/ALN.0b013e3181cd7942 20124985
    [Google Scholar]
  81. Joksovic P.M. Lunardi N. Jevtovic-Todorovic V. Todorovic S.M. Early exposure to general anesthesia with isoflurane downregulates inhibitory synaptic neurotransmission in the rat thalamus. Mol. Neurobiol. 2015 52 2 952 958 10.1007/s12035‑015‑9247‑6 26048671
    [Google Scholar]
  82. Talpos J.C. Chelonis J.J. Li M. Hanig J.P. Paule M.G. Early life exposure to extended general anesthesia with isoflurane and nitrous oxide reduces responsivity on a cognitive test battery in the nonhuman primate. Neurotoxicology 2019 70 80 90 10.1016/j.neuro.2018.11.005 30445043
    [Google Scholar]
  83. Briner A. Nikonenko I. De Roo M. Dayer A. Muller D. Vutskits L. Developmental Stage-dependent persistent impact of propofol anesthesia on dendritic spines in the rat medial prefrontal cortex. Anesthesiology 2011 115 2 282 293 10.1097/ALN.0b013e318221fbbd 21701379
    [Google Scholar]
  84. Pearn M.L. Hu Y. Niesman I.R. Patel H.H. Drummond J.C. Roth D.M. Akassoglou K. Patel P.M. Head B.P. Propofol neurotoxicity is mediated by p75 neurotrophin receptor activation. Anesthesiology 2012 116 2 352 361 10.1097/ALN.0b013e318242a48c 22198221
    [Google Scholar]
  85. Creeley C. Dikranian K. Dissen G. Martin L. Olney J. Brambrink A. Propofol-induced apoptosis of neurones and oligodendrocytes in fetal and neonatal rhesus macaque brain. Br J. Anaesth 2013 110 Suppl 1 i29 i38 (Suppl. 1) 10.1093/bja/aet173 23722059
    [Google Scholar]
  86. Huang J. Jing S. Chen X. Bao X. Du Z. Li H. Yang T. Fan X. Propofol administration during early postnatal life suppresses hippocampal neurogenesis. Mol. Neurobiol. 2016 53 2 1031 1044 10.1007/s12035‑014‑9052‑7 25577171
    [Google Scholar]
  87. Li D. Chen M. Meng T. Fei J. Hippocampal microglial activation triggers a neurotoxic-specific astrocyte response and mediates etomidate-induced long-term synaptic inhibition. J. Neuroinflammation 2020 17 1 109 10.1186/s12974‑020‑01799‑0 32264970
    [Google Scholar]
  88. Yon J.H. Daniel-Johnson J. Carter L.B. Jevtovic-Todorovic V. Anesthesia induces neuronal cell death in the developing rat brain via the intrinsic and extrinsic apoptotic pathways. Neuroscience 2005 135 3 815 827 10.1016/j.neuroscience.2005.03.064 16154281
    [Google Scholar]
  89. Ji M. Wang Z. Sun X. Tang H. Zhang H. Jia M. Qiu L. Zhang G. Peng Y.G. Yang J. Repeated neonatal sevoflurane exposure-induced developmental delays of parvalbumin interneurons and cognitive impairments are reversed by environmental enrichment. Mol. Neurobiol. 2017 54 5 3759 3770 10.1007/s12035‑016‑9943‑x 27251428
    [Google Scholar]
  90. Nozohouri E. Ahn Y. Zoubi S. Patel D. Archie S.R. Akter K.A. Siddique M.B. Huang J. Abbruscato T.J. Bickel U. The Acute Impact of Propofol on Blood–Brain Barrier Integrity in Mice. Pharm. Res. 2024 41 8 1599 1611 10.1007/s11095‑024‑03735‑w 39044046
    [Google Scholar]
  91. Almutairi M.M.A. Gong C. Xu Y.G. Chang Y. Shi H. Factors controlling permeability of the blood–brain barrier. Cell. Mol. Life Sci. 2016 73 1 57 77 10.1007/s00018‑015‑2050‑8 26403789
    [Google Scholar]
  92. Stratmann G. Sall J.W. May L.D.V. Bell J.S. Magnusson K.R. Rau V. Visrodia K.H. Alvi R.S. Ku B. Lee M.T. Dai R. Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats. Anesthesiology 2009 110 4 834 848 10.1097/ALN.0b013e31819c463d 19293705
    [Google Scholar]
  93. Gluncic V. Moric M. Chu Y. Hanko V. Li J. Lukić I.K. Lukić A. Edassery S.L. Kroin J.S. Persons A.L. Perry P. Kelly L. Shiveley T.J. Nice K. Napier C.T. Kordower J.H. Tuman K.J. In utero exposure to anesthetics alters neuronal migration pattern in developing cerebral cortex and causes postnatal behavioral deficits in rats. Cereb. Cortex 2019 29 12 5285 5301 10.1093/cercor/bhz065 31220224
    [Google Scholar]
  94. Yan J. Li J. Cheng Y. Zhang Y. Zhou Z. Zhang L. Jiang H. Dusp4 Contributes to Anesthesia Neurotoxicity via Mediated Neural Differentiation in Primates. Front. Cell Dev. Biol. 2020 8 786 10.3389/fcell.2020.00786 32974341
    [Google Scholar]
  95. Zanghi C.N. Jevtovic-Todorovic V. A holistic approach to anesthesia-induced neurotoxicity and its implications for future mechanistic studies. Neurotoxicol. Teratol. 2017 60 24 32 10.1016/j.ntt.2016.12.004 28039052
    [Google Scholar]
  96. Hogarth K. Tarazi D. Maynes J.T. The effects of general anesthetics on mitochondrial structure and function in the developing brain. Front. Neurol. 2023 14 1179823 10.3389/fneur.2023.1179823 37533472
    [Google Scholar]
  97. Boscolo A. Milanovic D. Starr J.A. Sanchez V. Oklopcic A. Moy L. Ori C.C. Erisir A. Jevtovic-Todorovic V. Early exposure to general anesthesia disturbs mitochondrial fission and fusion in the developing rat brain. Anesthesiology 2013 118 5 1086 1097 10.1097/ALN.0b013e318289bc9b 23411726
    [Google Scholar]
  98. Boscolo A. Ori C. Bennett J. Wiltgen B. Jevtovic-Todorovic V. Mitochondrial protectant pramipexole prevents sex-specific long-term cognitive impairment from early anaesthesia exposure in rats. Br J. Anaesth 2013 110 Suppl 1 i47 i52 10.1093/bja/aet073 23616588 (Suppl. 1)
    [Google Scholar]
  99. Yang Y. Hang W. Li J. Liu T. Hu Y. Fang F. Yan D. McQuillan P.M. Wang M. Hu Z. Effect of General Anesthetic Agents on Microglia. Aging Dis. 2024 15 3 1308 1328 37962460
    [Google Scholar]
  100. Yang Y. Liu T. Li J. Yan D. Hu Y. Wu P. Fang F. McQuillan P.M. Hang W. Leng J. Hu Z. General anesthetic agents induce neurotoxicity through astrocytes. Neural Regen. Res. 2024 19 6 1299 1307 10.4103/1673‑5374.385857 37905879
    [Google Scholar]
  101. Bell J.D. Stary C.M. Anesthetic neurotoxicity: an emerging role for glia in neuroprotection. J. Mol. Med. 2017 95 4 349 351 10.1007/s00109‑017‑1523‑7 28246725
    [Google Scholar]
  102. Ramadasan-Nair R. Hui J. Itsara L.S. Morgan P.G. Sedensky M.M. Mitochondrial function in astrocytes is essential for normal emergence from anesthesia in mice. Anesthesiology 2019 130 3 423 434 10.1097/ALN.0000000000002528 30707122
    [Google Scholar]
  103. Zhou B. Chen L. Liao P. Huang L. Chen Z. Liao D. Yang L. Wang J. Yu G. Wang L. Zhang J. Zuo Y. Liu J. Jiang R. Astroglial dysfunctions drive aberrant synaptogenesis and social behavioral deficits in mice with neonatal exposure to lengthy general anesthesia. PLoS Biol. 2019 17 8 e3000086 10.1371/journal.pbio.3000086 31433818
    [Google Scholar]
  104. Nagashima K. Zorumski C.F. Izumi Y. Propofol inhibits long-term potentiation but not long-term depression in rat hippocampal slices. Anesthesiology 2005 103 2 318 326 10.1097/00000542‑200508000‑00015 16052114
    [Google Scholar]
  105. Kato R. Tachibana K. Nishimoto N. Hashimoto T. Uchida Y. Ito R. Tsuruga K. Takita K. Morimoto Y. Neonatal exposure to sevoflurane causes significant suppression of hippocampal long-term potentiation in postgrowth rats. Anesth. Analg. 2013 117 6 1429 1435 10.1213/ANE.0b013e3182a8c709 24132013
    [Google Scholar]
  106. Haseneder R. Kratzer S. von Meyer L. Eder M. Kochs E. Rammes G. Isoflurane and sevoflurane dose-dependently impair hippocampal long-term potentiation. Eur. J. Pharmacol. 2009 623 1-3 47 51 10.1016/j.ejphar.2009.09.022 19765574
    [Google Scholar]
  107. Horan R. Sortica da Costa C. Nambyiah P. The persistent effects of anaesthesia on the brain. BJA Educ. 2023 23 8 304 311 10.1016/j.bjae.2023.04.001 37465234
    [Google Scholar]
  108. Maloney S.E. Creeley C.E. Hartman R.E. Yuede C.M. Zorumski C.F. Jevtovic-Todorovic V. Dikranian K. Noguchi K.K. Farber N.B. Wozniak D.F. Using animal models to evaluate the functional consequences of anesthesia during early neurodevelopment. Neurobiol. Learn. Mem. 2019 165 106834 10.1016/j.nlm.2018.03.014 29550366
    [Google Scholar]
  109. Raper J. Alvarado M.C. Murphy K.L. Baxter M.G. Multiple anesthetic exposure in infant monkeys alters emotional reactivity to an acute stressor. Anesthesiology 2015 123 5 1084 1092 10.1097/ALN.0000000000000851 26313293
    [Google Scholar]
  110. Neudecker V. Perez-Zoghbi J.F. Coleman K. Neuringer M. Robertson N. Bemis A. Glickman B. Schenning K.J. Fair D.A. Martin L.D. Dissen G.A. Brambrink A.M. Infant isoflurane exposure affects social behaviours, but does not impair specific cognitive domains in juvenile non-human primates. Br. J. Anaesth. 2021 126 2 486 499 10.1016/j.bja.2020.10.015 33198945
    [Google Scholar]
  111. Diana P. Joksimovic S.M. Faisant A. Jevtovic-Todorovic V. Early exposure to general anesthesia impairs social and emotional development in rats. Mol. Neurobiol. 2020 57 1 41 50 10.1007/s12035‑019‑01755‑x 31494825
    [Google Scholar]
  112. Coleman K. Robertson N.D. Dissen G.A. Neuringer M.D. Martin L.D. Cuzon Carlson V.C. Kroenke C. Fair D. Brambrink A.M. Isoflurane anesthesia has long-term consequences on motor and behavioral development in infant rhesus macaques. Anesthesiology 2017 126 1 74 84 10.1097/ALN.0000000000001383 27749311
    [Google Scholar]
  113. Sprung J. Flick R.P. Wilder R.T. Katusic S.K. Pike T.L. Dingli M. Gleich S.J. Schroeder D.R. Barbaresi W.J. Hanson A.C. Warner D.O. Anesthesia for cesarean delivery and learning disabilities in a population-based birth cohort. Anesthesiology 2009 111 2 302 310 10.1097/ALN.0b013e3181adf481 19602960
    [Google Scholar]
  114. Andropoulos D.B. Ahmad H.B. Haq T. Brady K. Stayer S.A. Meador M.R. Hunter J.V. Rivera C. Voigt R.G. Turcich M. He C.Q. Shekerdemian L.S. Dickerson H.A. Fraser C.D. Dean McKenzie E. Heinle J.S. Blaine Easley R. The association between brain injury, perioperative anesthetic exposure, and 12‐month neurodevelopmental outcomes after neonatal cardiac surgery: A retrospective cohort study. Paediatr. Anaesth. 2014 24 3 266 274 10.1111/pan.12350 24467569
    [Google Scholar]
  115. Bartels M. Althoff R.R. Boomsma D.I. Anesthesia and cognitive performance in children: No evidence for a causal relationship. Twin Res. Hum. Genet. 2009 12 3 246 253 10.1375/twin.12.3.246 19456216
    [Google Scholar]
  116. DiMaggio C. Sun L.S. Kakavouli A. Byrne M.W. Li G. A retrospective cohort study of the association of anesthesia and hernia repair surgery with behavioral and developmental disorders in young children. J. Neurosurg. Anesthesiol. 2009 21 4 286 291 10.1097/ANA.0b013e3181a71f11 19955889
    [Google Scholar]
  117. Kalkman C.J. Peelen L. Moons K.G. Veenhuizen M. Bruens M. Sinnema G. de Jong T.P. Behavior and development in children and age at the time of first anesthetic exposure. Anesthesiology 2009 110 4 805 812 10.1097/ALN.0b013e31819c7124 19293699
    [Google Scholar]
  118. Flick R.P. Katusic S.K. Colligan R.C. Wilder R.T. Voigt R.G. Olson M.D. Sprung J. Weaver A.L. Schroeder D.R. Warner D.O. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics 2011 128 5 e1053 e1061 10.1542/peds.2011‑0351 21969289
    [Google Scholar]
  119. Fan Q. Cai Y. Chen K. Li W. Prognostic study of sevoflurane-based general anesthesia on cognitive function in children. J. Anesth. 2013 27 4 493 499 10.1007/s00540‑013‑1566‑z 23386252
    [Google Scholar]
  120. Ing C. DiMaggio C. Whitehouse A. Hegarty M.K. Brady J. von Ungern-Sternberg B.S. Davidson A. Wood A.J.J. Li G. Sun L.S. Long-term differences in language and cognitive function after childhood exposure to anesthesia. Pediatrics 2012 130 3 e476 e485 10.1542/peds.2011‑3822 22908104
    [Google Scholar]
  121. O’Leary J.D. Janus M. Duku E. Wijeysundera D.N. To T. Li P. Maynes J.T. Crawford M.W. A Population-based study evaluating the association between surgery in early life and child development at primary school entry. Anesthesiology 2016 125 2 272 279 10.1097/ALN.0000000000001200 27433745
    [Google Scholar]
  122. Wilder R.T. Flick R.P. Sprung J. Katusic S.K. Barbaresi W.J. Mickelson C. Gleich S.J. Schroeder D.R. Weaver A.L. Warner D.O. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology 2009 110 4 796 804 10.1097/01.anes.0000344728.34332.5d 19293700
    [Google Scholar]
  123. Sun L.S. Li G. Miller T.L.K. Salorio C. Byrne M.W. Bellinger D.C. Ing C. Park R. Radcliffe J. Hays S.R. DiMaggio C.J. Cooper T.J. Rauh V. Maxwell L.G. Youn A. McGowan F.X. Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood. JAMA 2016 315 21 2312 2320 10.1001/jama.2016.6967 27272582
    [Google Scholar]
  124. Davidson A.J. Disma N. de Graaff J.C. Withington D.E. Dorris L. Bell G. Stargatt R. Bellinger D.C. Schuster T. Arnup S.J. Hardy P. Hunt R.W. Takagi M.J. Giribaldi G. Hartmann P.L. Salvo I. Morton N.S. von Ungern Sternberg B.S. Locatelli B.G. Wilton N. Lynn A. Thomas J.J. Polaner D. Bagshaw O. Szmuk P. Absalom A.R. Frawley G. Berde C. Ormond G.D. Marmor J. McCann M.E. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): An international multicentre, randomised controlled trial. Lancet 2016 387 10015 239 250 10.1016/S0140‑6736(15)00608‑X 26507180
    [Google Scholar]
  125. McCann M.E. de Graaff J.C. Dorris L. Disma N. Withington D. Bell G. Grobler A. Stargatt R. Hunt R.W. Sheppard S.J. Marmor J. Giribaldi G. Bellinger D.C. Hartmann P.L. Hardy P. Frawley G. Izzo F. von Ungern Sternberg B.S. Lynn A. Wilton N. Mueller M. Polaner D.M. Absalom A.R. Szmuk P. Morton N. Berde C. Soriano S. Davidson A.J. Davidson A.J. Frawley G. Hardy P. Arnup S. Grobler A. Lee K. Hunt R.W. Stargatt R. Sheppard S.J. Ormond G.D. Hartmann P.L. Takagi M.J. Taylor K. Malarbi S. Doyle M. Ragg P. Costi D. von Ungern-Sternberg B. Wilton N.C. Knottenbelt G. Withington D. Furue K. Gagnon H. Disma N. Mameli L. Giribaldi G. Pini Prato A. Mattioli G. Wolfler A. Izzo F. Bova S.M. Krachmalnicoff A. Guuva C. de Graaff J.C. van der Werff D.B.M. van Gool J.T.D.G. van Loon K. Kalkman C.J. van Baar A.L. Absalom A.R. Hoekstra F.M. Volkers M. Oostra M. Bell G. Dorris L. Morton N.S. Pownall J. Waldman J. Hind R. Symonds J.D. Bagshaw O. McCann M.E. Berde C. Soriano S. Sethna N. Kovatsis P. Cravero J. Bellinger D. Marmor J. Lynn A. Ivanova I. Hunyady A. Verma S. Polaner D. Thomas J. Mueller M. Haret D. Szmuk P. Steiner J. Kravitz B. Farrow-Gillespie A. Suresh S. Hays S. Taenzer A. Maxwell L. Williams R. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): An international, multicentre, randomised, controlled equivalence trial. Lancet 2019 393 10172 664 677 10.1016/S0140‑6736(18)32485‑1 30782342
    [Google Scholar]
  126. Warner D.O. Zaccariello M.J. Katusic S.K. Schroeder D.R. Hanson A.C. Schulte P.J. Buenvenida S.L. Gleich S.J. Wilder R.T. Sprung J. Hu D. Voigt R.G. Paule M.G. Chelonis J.J. Flick R.P. Neuropsychological and behavioral outcomes after exposure of young children to procedures requiring general anesthesia. Anesthesiology 2018 129 1 89 105 10.1097/ALN.0000000000002232 29672337
    [Google Scholar]
  127. Ing C. Jackson W.M. Zaccariello M.J. Goldberg T.E. McCann M.E. Grobler A. Davidson A. Sun L. Li G. Warner D.O. Prospectively assessed neurodevelopmental outcomes in studies of anaesthetic neurotoxicity in children: a systematic review and meta-analysis. Br. J. Anaesth. 2021 126 2 433 444 10.1016/j.bja.2020.10.022 33250180
    [Google Scholar]
  128. Raper J. De Biasio J.C. Murphy K.L. Alvarado M.C. Baxter M.G. Persistent alteration in behavioural reactivity to a mild social stressor in rhesus monkeys repeatedly exposed to sevoflurane in infancy. Br. J. Anaesth. 2018 120 4 761 767 10.1016/j.bja.2018.01.014 29576116
    [Google Scholar]
  129. Huang L. Yang G. Repeated exposure to ketamine-xylazine during early development impairs motor learning-dependent dendritic spine plasticity in adulthood. Anesthesiology 2015 122 4 821 831 10.1097/ALN.0000000000000579 25575163
    [Google Scholar]
  130. Tolaymat Y. Doré S. Griffin H.W. Shih S. Edwards M.E. Weiss M.D. Inhaled gases for neuroprotection of neonates: A review. Front Pediatr. 2020 7 558 10.3389/fped.2019.00558 32047729
    [Google Scholar]
  131. Wang K. Wang Y. Zhang T. Chang B. Fu D. Chen X. The role of intravenous anesthetics for Neuro: Protection or toxicity? Neurosci. Bull. 2024 39153174
    [Google Scholar]
  132. Wu L. Zhao H. Weng H. Ma D. Lasting effects of general anesthetics on the brain in the young and elderly: “Mixed picture” of neurotoxicity, neuroprotection and cognitive impairment. J. Anesth. 2019 33 2 321 335 10.1007/s00540‑019‑02623‑7 30859366
    [Google Scholar]
  133. Vutskits L. General anesthetics in brain injury: Friends or foes? Curr. Pharm. Des. 2014 20 26 4203 4210 24025058
    [Google Scholar]
  134. Paus T. Keshavan M. Giedd J.N. Why do many psychiatric disorders emerge during adolescence? Nat. Rev. Neurosci. 2008 9 12 947 957 10.1038/nrn2513 19002191
    [Google Scholar]
  135. Kessler R. C. Angermeyer M. Anthony J. C. DE Graaf R. Demyttenaere K. Gasquet I. DE Girolamo G. Gluzman S. Gureje O. Haro J. M. Kawakami N. Karam A. Levinson D. Medina Mora M. E. Oakley Browne M. A. Posada-Villa J. Stein D. J. Adley Tsang C. H. Aguilar-Gaxiola S. Alonso J. Lee S. Heeringa S. Pennell B. E. Berglund P. Gruber M. J. Petukhova M. Chatterji S. Ustün T. B. Lifetime prevalence and age-of-onset distributions of mental disorders in the World Health Organization’s World Mental Health Survey Initiative. World Psychiatry 2007 6 3 168 176 18188442
    [Google Scholar]
  136. Rehm J. Shield K.D. Global Burden of disease and the impact of mental and addictive disorders. Curr. Psychiatry Rep. 2019 21 2 10 10.1007/s11920‑019‑0997‑0 30729322
    [Google Scholar]
  137. Xu J. Wang J. Wimo A. Qiu C. The economic burden of mental disorders in China, 2005–2013: Implications for health policy. BMC Psychiatry 2016 16 1 137 10.1186/s12888‑016‑0839‑0 27169936
    [Google Scholar]
  138. Doernberg E. Hollander E. Neurodevelopmental Disorders (ASD and ADHD): DSM-5, ICD-10, and ICD-11. CNS Spectr. 2016 21 4 295 299 10.1017/S1092852916000262 27364515
    [Google Scholar]
  139. Forrest M.P. Parnell E. Penzes P. Dendritic structural plasticity and neuropsychiatric disease. Nat. Rev. Neurosci. 2018 19 4 215 234 10.1038/nrn.2018.16 29545546
    [Google Scholar]
  140. Taber K.H. Hurley R.A. Yudofsky S.C. Diagnosis and treatment of neuropsychiatric disorders. Annu. Rev. Med. 2010 61 1 121 133 10.1146/annurev.med.051408.105018 19824816
    [Google Scholar]
  141. Niebrzydowska A. Grabowski J. Medication-induced psychotic disorder. A review of selected drugs side effects. Psychiatr. Danub. 2022 34 1 11 18 10.24869/psyd.2022.11 35467605
    [Google Scholar]
  142. Leucht S. Priller J. Davis J.M. Antipsychotic drugs: A concise review of history, classification, indications, mechanism, efficacy, side effects, dosing, and clinical application. Am. J. Psychiatry 2024 181 10 865 878 10.1176/appi.ajp.20240738 39350614
    [Google Scholar]
  143. Wilkinson S.T. Sanacora G. A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems. Drug Discov. Today 2019 24 2 606 615 10.1016/j.drudis.2018.11.007 30447328
    [Google Scholar]
  144. Ohgi Y. Futamura T. Hashimoto K. Glutamate signaling in synaptogenesis and NMDA receptors as potential therapeutic targets for psychiatric disorders. Curr. Mol. Med. 2015 15 3 206 221 10.2174/1566524015666150330143008 25817855
    [Google Scholar]
  145. Thompson S.M. Modulators of GABAA receptor-mediated inhibition in the treatment of neuropsychiatric disorders: past, present, and future. Neuropsychopharmacology 2024 49 1 83 95 10.1038/s41386‑023‑01728‑8 37709943
    [Google Scholar]
  146. Heresco-Levy U. Lerer B. Synergistic psychedelic - NMDAR modulator treatment for neuropsychiatric disorders. Mol. Psychiatry 2024 29 1 146 152 10.1038/s41380‑023‑02312‑8 37945694
    [Google Scholar]
  147. Stein M.B. Rothbaum B.O. 175 years of progress in PTSD therapeutics: Learning from the past. Am. J. Psychiatry 2018 175 6 508 516 10.1176/appi.ajp.2017.17080955 29869547
    [Google Scholar]
  148. Gillespie R.D. A critical review: Narcosis therapy. J. Neurol. Neurosurg. Psychiatry 1939 2 1 45 65 10.1136/jnnp.2.1.45 21610942
    [Google Scholar]
  149. McKenzie A. Anaesthetic and other treatments of shell shock: World War I and beyond. J. R. Army Med. Corps 2012 158 1 29 33 10.1136/jramc‑158‑01‑07 22545370
    [Google Scholar]
  150. Miller D.H. Clancy J. Cumming E. A comparison between unidirectional current nonconvulsive electrical stimulation given with Reiter’s machine, standard alternating current electro-shock (Cerletti method), and pentothal in chronic schizophrenia. Am. J. Psychiatry 1953 109 8 617 620 10.1176/ajp.109.8.617 13030821
    [Google Scholar]
  151. Lambourn J. Gill D. A controlled comparison of simulated and real ECT. Br. J. Psychiatry 1978 133 6 514 519 10.1192/bjp.133.6.514 367479
    [Google Scholar]
  152. Johnstone E. Lawler P. Stevens M. Deakin J.F.W. Frith C.D. Mcpherson K. Crow T.J. The northwick park electroconvulsive therapy trial. Lancet 1980 316 8208-8209 1317 1320 10.1016/S0140‑6736(80)92393‑4 6109147
    [Google Scholar]
  153. Freeman C.P.L. Basson J.V. Crighton A. Double-blind controlled trail of electroconvulsive therapy (E.C.T.) and simulated E.C.T. in depressive illness. Lancet 1978 311 8067 738 740 10.1016/S0140‑6736(78)90857‑7 76748
    [Google Scholar]
  154. Langer G. Neumark J. Koinig G. Graf M. Schönbeck G. Rapid psychotherapeutic effects of anesthesia with isoflurane (ES narcotherapy) in treatment-refractory depressed patients. Neuropsychobiology 1985 14 3 118 120 10.1159/000118216 3831799
    [Google Scholar]
  155. Carl C. Engelhardt W. Teichmann G. Fuchs G. Open comparative study with treatment-refractory depressed patients: electroconvulsive therapy--anesthetic therapy with isoflurane (preliminary report). Pharmacopsychiatry 1988 21 6 432 433 10.1055/s‑2007‑1017040 3244786
    [Google Scholar]
  156. Langer G. Karazman R. Neumark J. Saletu B. Schönbeck G. Grünberger J. Dittrich R. Petricek W. Hoffmann P. Linzmayer L. Anderer P. Steinberger K. Isoflurane narcotherapy in depressive patients refractory to conventional antidepressant drug treatment. A double-blind comparison with electroconvulsive treatment. Neuropsychobiology 1995 31 4 182 194 10.1159/000119190 7659199
    [Google Scholar]
  157. Weeks H.R. Tadler S.C. Smith K.W. Iacob E. Saccoman M. White A.T. Landvatter J.D. Chelune G.J. Suchy Y. Clark E. Cahalan M.K. Bushnell L. Sakata D. Light A.R. Light K.C. Antidepressant and neurocognitive effects of isoflurane anesthesia versus electroconvulsive therapy in refractory depression. PLoS One 2013 8 7 e69809 10.1371/journal.pone.0069809 23922809
    [Google Scholar]
  158. Skolnick P. Layer R. Popik P. Nowak G. Paul I. Trullas R. Adaptation of N-methyl-D-aspartate (NMDA) receptors following antidepressant treatment: implications for the pharmacotherapy of depression. Pharmacopsychiatry 1996 29 1 23 26 10.1055/s‑2007‑979537 8852530
    [Google Scholar]
  159. Berman R.M. Cappiello A. Anand A. Oren D.A. Heninger G.R. Charney D.S. Krystal J.H. Antidepressant effects of ketamine in depressed patients. Biol. Psychiatry 2000 47 4 351 354 10.1016/S0006‑3223(99)00230‑9 10686270
    [Google Scholar]
  160. Shen Z. Gao D. Lv X. Wang H. Yue W. A meta-analysis of the effects of ketamine on suicidal ideation in depression patients. Transl. Psychiatry 2024 14 1 248 10.1038/s41398‑024‑02973‑1 38858391
    [Google Scholar]
  161. Menon V. Varadharajan N. Faheem A. Andrade C. Ketamine vs electroconvulsive therapy for major depressive episode. JAMA Psychiatry 2023 80 6 639 642 10.1001/jamapsychiatry.2023.0562 37043224
    [Google Scholar]
  162. Zanos P. Gould T.D. Mechanisms of ketamine action as an antidepressant. Mol. Psychiatry 2018 23 4 801 811 10.1038/mp.2017.255 29532791
    [Google Scholar]
  163. Zanos P. Brown K.A. Georgiou P. Yuan P. Zarate C.A. Thompson S.M. Gould T.D. NMDA receptor activation-dependent antidepressant-relevant behavioral and synaptic actions of ketamine. J. Neurosci. 2023 43 6 1038 1050 10.1523/JNEUROSCI.1316‑22.2022 36596696
    [Google Scholar]
  164. Nagele P. Duma A. Kopec M. Gebara M.A. Parsoei A. Walker M. Janski A. Panagopoulos V.N. Cristancho P. Miller J.P. Zorumski C.F. Conway C.R. Nitrous oxide for treatment-resistant major depression: A proof-of-concept trial. Biol. Psychiatry 2015 78 1 10 18 10.1016/j.biopsych.2014.11.016 25577164
    [Google Scholar]
  165. Yang C. Hashimoto K. Combination of nitrous oxide with isoflurane or scopolamine for treatment-resistant major depression. Clin. Psychopharmacol. Neurosci. 2015 13 1 118 120 10.9758/cpn.2015.13.1.118 25912547
    [Google Scholar]
  166. Zorumski C.F. Nagele P. Mennerick S. Conway C.R. Treatment-resistant major depression: Rationale for NMDA receptors as targets and nitrous oxide as therapy. Front. Psychiatry 2015 6 172 10.3389/fpsyt.2015.00172 26696909
    [Google Scholar]
  167. Nagele P. Palanca B.J. Gott B. Brown F. Barnes L. Nguyen T. Xiong W. Salloum N.C. Espejo G.D. Lessov-Schlaggar C.N. Jain N. Cheng W.W.L. Komen H. Yee B. Bolzenius J.D. Janski A. Gibbons R. Zorumski C.F. Conway C.R. A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression. Sci. Transl. Med. 2021 13 597 eabe1376 10.1126/scitranslmed.abe1376 34108247
    [Google Scholar]
  168. de Leon V.C. Kumar A. Nagele P. Palanca B.J. Gott B. Janski A. Zorumski C.F. Conway C.R. Nitrous oxide reduced suicidal ideation in treatment-resistant major depression in exploratory analysis. J. Clin. Psychiatry 2023 84 5 84 37585253
    [Google Scholar]
  169. Conway C.R. Palanca B.J.A. Zeffiro T. Gott B.M. Brown F. de Leon V. Nitrous oxide alters functional connectivity in medial limbic structures in treatment-resistant major depression. medRxiv 2024 10.1101/2024.08.12.24311729
    [Google Scholar]
  170. Mickey B.J. White A.T. Arp A.M. Leonardi K. Torres M.M. Larson A.L. Odell D.H. Whittingham S.A. Beck M.M. Jessop J.E. Sakata D.J. Bushnell L.A. Pierson M.D. Solzbacher D. Kendrick E.J. Weeks H.R. Light A.R. Light K.C. Tadler S.C. Propofol for treatment-resistant depression: A pilot study. Int. J. Neuropsychopharmacol. 2018 21 12 1079 1089 10.1093/ijnp/pyy085 30260415
    [Google Scholar]
  171. Tadler S.C. Jones K.G. Lybbert C. Huang J.C. Jawish R. Solzbacher D. Propofol for treatment resistant depression: A randomized controlled trial. medRxiv 2023 10.1101/2023.09.12.23294678
    [Google Scholar]
  172. Lin C. Ma D. Song X. Zhao T. Shi Z. Ling N. Qin J. Zhou Q. Wu L. Wang Y. Sevoflurane ameliorates schizophrenia in a mouse model and patients: Pre-clinical and clinical feasibility study. Curr. Neuropharmacol. 2022 20 12 2369 2380 10.2174/1570159X20666220310115846 35272593
    [Google Scholar]
  173. Fox F.L. Michael Bostwick J. Propofol sedation of refractory delirious mania. Psychosomatics 1997 38 3 288 290 10.1016/S0033‑3182(97)71466‑X 9136258
    [Google Scholar]
  174. Chalwin R. Propofol infusion for the retrieval of the acutely psychotic patient. Air Med. J. 2012 31 1 33 35 10.1016/j.amj.2011.06.008 22225562
    [Google Scholar]
  175. Powell J.G. Garland S. Preston K. Piszczatoski C. Brexanolone (Zulresso): Finally, an FDA-approved treatment for postpartum depression. Ann. Pharmacother. 2020 54 2 157 163 10.1177/1060028019873320 31476884
    [Google Scholar]
  176. De S.K. Ganaxolone: First FDA-approved medicine for the treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder. Curr. Med. Chem. 2024 31 4 388 392 10.2174/0929867330666230320123952 36959132
    [Google Scholar]
  177. Shouan A. Grover S. Adjunctive intranasal esketamine in treatment-resistant depression. JAMA Psychiatry 2018 75 6 654 10.1001/jamapsychiatry.2018.0690 29801086
    [Google Scholar]
  178. Capuzzi E. Caldiroli A. Capellazzi M. Tagliabue I. Marcatili M. Colmegna F. Clerici M. Buoli M. Dakanalis A. Long-Term efficacy of intranasal esketamine in treatment-resistant major depression: A systematic review. Int. J. Mol. Sci. 2021 22 17 9338 10.3390/ijms22179338 34502248
    [Google Scholar]
  179. McIntyre R.S. Jain R. Glutamatergic modulators for major depression from theory to clinical use. CNS Drugs 2024 38 11 869 890 10.1007/s40263‑024‑01114‑y 39150594
    [Google Scholar]
  180. Morris-Rosendahl D.J. Crocq M.A. Neurodevelopmental disorders—the history and future of a diagnosticconcept. Dialogues Clin. Neurosci. 2020 22 1 65 72 10.31887/DCNS.2020.22.1/macrocq 32699506
    [Google Scholar]
  181. Mollon J. Almasy L. Jacquemont S. Glahn D.C. The contribution of copy number variants to psychiatric symptoms and cognitive ability. Mol. Psychiatry 2023 28 4 1480 1493 10.1038/s41380‑023‑01978‑4 36737482
    [Google Scholar]
  182. Drakesmith M. Parker G.D. Smith J. Linden S.C. Rees E. Williams N. Owen M.J. van den Bree M. Hall J. Jones D.K. Linden D.E.J. Genetic risk for schizophrenia and developmental delay is associated with shape and microstructure of midline white-matter structures. Transl. Psychiatry 2019 9 1 102 10.1038/s41398‑019‑0440‑7 30804328
    [Google Scholar]
  183. Owen M.J. O’Donovan M.C. Schizophrenia and the neurodevelopmental continuum: Evidence from genomics. World Psychiatry 2017 16 3 227 235 10.1002/wps.20440 28941101
    [Google Scholar]
  184. Singh T. Walters J.T.R. Johnstone M. Curtis D. Suvisaari J. Torniainen M. Rees E. Iyegbe C. Blackwood D. McIntosh A.M. Kirov G. Geschwind D. Murray R.M. Di Forti M. Bramon E. Gandal M. Hultman C.M. Sklar P. Palotie A. Sullivan P.F. O’Donovan M.C. Owen M.J. Barrett J.C. The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability. Nat. Genet. 2017 49 8 1167 1173 10.1038/ng.3903 28650482
    [Google Scholar]
  185. Girirajan S. Brkanac Z. Coe B.P. Baker C. Vives L. Vu T.H. Shafer N. Bernier R. Ferrero G.B. Silengo M. Warren S.T. Moreno C.S. Fichera M. Romano C. Raskind W.H. Eichler E.E. Relative burden of large CNVs on a range of neurodevelopmental phenotypes. PLoS Genet. 2011 7 11 e1002334 10.1371/journal.pgen.1002334 22102821
    [Google Scholar]
  186. Goel A. Portera-Cailliau C. Autism in the Balance: Elevated E-I Ratio as a homeostatic stabilization of synaptic drive. Neuron 2019 101 4 543 545 10.1016/j.neuron.2019.01.033 30790531
    [Google Scholar]
  187. Canitano R. Palumbi R. Excitation/inhibition modulators in autism spectrum disorder: Current clinical research. Front. Neurosci. 2021 15 753274 10.3389/fnins.2021.753274 34916897
    [Google Scholar]
  188. Berry-Kravis E.M. Lindemann L. Jønch A.E. Apostol G. Bear M.F. Carpenter R.L. Crawley J.N. Curie A. Des Portes V. Hossain F. Gasparini F. Gomez-Mancilla B. Hessl D. Loth E. Scharf S.H. Wang P.P. Von Raison F. Hagerman R. Spooren W. Jacquemont S. Drug development for neurodevelopmental disorders: Lessons learned from fragile X syndrome. Nat. Rev. Drug Discov. 2018 17 4 280 299 10.1038/nrd.2017.221 29217836
    [Google Scholar]
  189. Faden J. Musselman M. Citrome L. Sublingual dexmedetomidine: Repurposing an anesthetic as an anti-agitation agent. Expert Rev. Neurother. 2023 23 2 97 106 10.1080/14737175.2023.2174430 36707066
    [Google Scholar]
  190. Li C.T. Yang K.C. Lin W.C. Glutamatergic dysfunction and glutamatergic compounds for major psychiatric disorders: Evidence from clinical neuroimaging studies. Front. Psychiatry 2019 9 767 10.3389/fpsyt.2018.00767 30733690
    [Google Scholar]
  191. Howes O.D. Rogdaki M. Findon J.L. Wichers R.H. Charman T. King B.H. Loth E. McAlonan G.M. McCracken J.T. Parr J.R. Povey C. Santosh P. Wallace S. Simonoff E. Murphy D.G. Autism spectrum disorder: Consensus guidelines on assessment, treatment and research from the British Association for Psychopharmacology. J. Psychopharmacol. 2018 32 1 3 29 10.1177/0269881117741766 29237331
    [Google Scholar]
  192. Choi M. Ko S.Y. Seo J.Y. Kim D.G. Lee H. Chung H. Son H. Autistic-like social deficits in hippocampal MeCP2 knockdown rat models are rescued by ketamine. BMB Rep. 2022 55 5 238 243 10.5483/BMBRep.2022.55.5.038 35410641
    [Google Scholar]
  193. Cai Y. Wang L. Xiao R. Li X. He X. Gao J. Xu H. Fan X. Autism-like behavior in the BTBR mouse model of autism is improved by propofol. Neuropharmacology 2017 118 175 187 10.1016/j.neuropharm.2017.03.021 28341205
    [Google Scholar]
  194. Dobrovolsky A.P. Gedzun V.R. Bogin V.I. Ma D. Ichim T.E. Sukhanova I.A. Malyshev A.V. Dubynin V.A. Beneficial effects of xenon inhalation on behavioral changes in a valproic acid-induced model of autism in rats. J. Transl. Med. 2019 17 1 400 10.1186/s12967‑019‑02161‑6 31796043
    [Google Scholar]
  195. Wink L.K. Reisinger D.L. Horn P. Shaffer R.C. O’Brien K. Schmitt L. Dominick K.R. Pedapati E.V. Erickson C.A. Brief Report: Intranasal Ketamine in Adolescents and Young Adults with Autism Spectrum Disorder—Initial Results of a Randomized, Controlled, Crossover, Pilot Study. J. Autism Dev. Disord. 2021 51 4 1392 1399 10.1007/s10803‑020‑04542‑z 32642957
    [Google Scholar]
  196. Patel D.C. Tewari B.P. Chaunsali L. Sontheimer H. Neuron–glia interactions in the pathophysiology of epilepsy. Nat. Rev. Neurosci. 2019 20 5 282 297 10.1038/s41583‑019‑0126‑4 30792501
    [Google Scholar]
  197. Perks A. Cheema S. Mohanraj R. Anaesthesia and epilepsy. Br. J. Anaesth. 2012 108 4 562 571 10.1093/bja/aes027 22408271
    [Google Scholar]
  198. Au Y.K. Kananeh M.F. Rahangdale R. Moore T.E. Panza G.A. Gaspard N. Hirsch L.J. Fernandez A. Shah S.O. Treatment of refractory status epilepticus with continuous intravenous anesthetic drugs. JAMA Neurol. 2024 81 5 534 548 10.1001/jamaneurol.2024.0108 38466294
    [Google Scholar]
  199. Madžar D. Reindl C. Giede-Jeppe A. Bobinger T. Sprügel M.I. Knappe R.U. Hamer H.M. Huttner H.B. Impact of timing of continuous intravenous anesthetic drug treatment on outcome in refractory status epilepticus. Crit. Care 2018 22 1 317 10.1186/s13054‑018‑2235‑2 30463604
    [Google Scholar]
  200. Zeiler F.A. Zeiler K.J. Teitelbaum J. Gillman L.M. West M. Modern inhalational anesthetics for refractory status epilepticus. Can. J. Neurol. Sci. 2015 42 2 106 115 10.1017/cjn.2014.121 25572922
    [Google Scholar]
  201. Zaytseva A. Bouckova E. Wiles M.J. Wustrau M.H. Schmidt I.G. Mendez-Vazquez H. Khatri L. Kim S. Ketamine’s rapid antidepressant effects are mediated by Ca2+-permeable AMPA receptors. eLife 2023 12 e86022 10.7554/eLife.86022 37358072
    [Google Scholar]
  202. Hollinger A. Rüst C.A. Riegger H. Gysi B. Tran F. Brügger J. Huber J. Toft K. Surbeck M. Schmid H.R. Rentsch K. Steiner L. Siegemund M. Ketamine vs. haloperidol for prevention of cognitive dysfunction and postoperative delirium: A phase IV multicentre randomised placebo-controlled double-blind clinical trial. J. Clin. Anesth. 2021 68 110099 10.1016/j.jclinane.2020.110099 33120302
    [Google Scholar]
  203. Fagerholm E.D. Leech R. Williams S. Zarate C.A. Moran R.J. Gilbert J.R. Fine-tuning neural excitation/inhibition for tailored ketamine use in treatment-resistant depression. Transl. Psychiatry 2021 11 1 335 10.1038/s41398‑021‑01442‑3 34052834
    [Google Scholar]
  204. Gerhard D.M. Pothula S. Liu R.J. Wu M. Li X.Y. Girgenti M.J. Taylor S.R. Duman C.H. Delpire E. Picciotto M. Wohleb E.S. Duman R.S. GABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions. J. Clin. Invest. 2020 130 3 1336 1349 10.1172/JCI130808 31743111
    [Google Scholar]
  205. Luscher B. Feng M. Jefferson S.J. Antidepressant mechanisms of ketamine: Focus on GABAergic inhibition. Adv. Pharmacol. 2020 89 43 78 10.1016/bs.apha.2020.03.002 32616214
    [Google Scholar]
  206. Aleksandrova L.R. Phillips A.G. Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics. Trends Pharmacol. Sci. 2021 42 11 929 942 10.1016/j.tips.2021.08.003 34565579
    [Google Scholar]
  207. You S. Wu Y. Guo Y. Wu M. Ran M. Cao F. Hao X. Yang L. Zhang H. Mi W. Tong L. Sevoflurane exerts antidepressant-like effects via the BDNF-TrkB pathway. Behav. Brain Res. 2024 463 114918 10.1016/j.bbr.2024.114918 38387696
    [Google Scholar]
  208. Guo F. Zhang B. Shen F. Li Q. Song Y. Li T. Zhang Y. Du W. Li Y. Liu W. Cao H. Zhou X. Zheng Y. Zhu S. Li Y. Liu Z. Sevoflurane acts as an antidepressant by suppression of GluN2D‐containing NMDA receptors on interneurons. Br. J. Pharmacol. 2024 181 18 3483 3502 10.1111/bph.16420 38779864
    [Google Scholar]
  209. Yan J. Hang B.N. Ma L.H. Lin J.T. Zhou Y. Jiao X.H. Yuan Y.X. Shao K.J. Zhang L.M. Xue Q. Li Z.Y. Zhang H.X. Cao J.L. Li S. Zheng H. Wu Y.Q. GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol. Mol. Neurobiol. 2023 60 10 5789 5804 10.1007/s12035‑023‑03445‑1 37349621
    [Google Scholar]
  210. Wu M. Li A. Guo Y. Cao F. You S. Cao J. Mi W. Tong L. GABAergic neurons in the nucleus accumbens core mediate the antidepressant effects of sevoflurane. Eur. J. Pharmacol. 2023 946 175627 10.1016/j.ejphar.2023.175627 36868292
    [Google Scholar]
  211. Rabiner E.A. Imaging of striatal dopamine release elicited with NMDA antagonists: Is there anything there to be seen? J. Psychopharmacol. 2007 21 3 253 258 10.1177/0269881107077767 17591653
    [Google Scholar]
  212. Masuzawa M. Nakao S. Miyamoto E. Yamada M. Murao K. Nishi K. Shingu K. Pentobarbital inhibits ketamine-induced dopamine release in the rat nucleus accumbens: A microdialysis study. Anesth. Analg. 2003 96 1 148 152 10.1213/00000539‑200301000‑00030 12505941
    [Google Scholar]
  213. Westphalen R.I. Desai K.M. Hemmings H.C. Presynaptic inhibition of the release of multiple major central nervous system neurotransmitter types by the inhaled anaesthetic isoflurane. Br. J. Anaesth. 2013 110 4 592 599 10.1093/bja/aes448 23213036
    [Google Scholar]
  214. Martin D.C. Watkins C.A. Adams R.J. Nason L.A. Anesthetic effects on 5-hydroxytryptamine uptake by rat brain synaptosomes. Brain Res. 1988 455 2 360 365 10.1016/0006‑8993(88)90095‑9 2969767
    [Google Scholar]
  215. Zhu X.N. Li J. Qiu G.L. Wang L. Lu C. Guo Y.G. Yang K.X. Cai F. Xu T. Yuan T.F. Hu J. Propofol exerts anti-anhedonia effects via inhibiting the dopamine transporter. Neuron 2023 111 10 1626 1636.e6 10.1016/j.neuron.2023.02.017 36917979
    [Google Scholar]
  216. zivković, S. Autoimmune neurologic disorders. Curr. Neuropharmacol. 2011 9 3 399 10.2174/157015911796557993 22379453
    [Google Scholar]
  217. Aoun R. Gratch D. Kaminetzky D. Kister I. Immune checkpoint inhibitors in patients with pre-existing neurologic autoimmune disorders. Curr. Neurol. Neurosci. Rep. 2023 23 11 735 750 10.1007/s11910‑023‑01306‑x 37870664
    [Google Scholar]
  218. Flanagan E. López-Chiriboga A. Diagnostic and therapeutic approach to autoimmune neurologic disorders. Semin. Neurol. 2018 38 3 392 402 10.1055/s‑0038‑1660819 30011418
    [Google Scholar]
  219. Kamm C. Zettl U.K. Autoimmune disorders affecting both the central and peripheral nervous system. Autoimmun. Rev. 2012 11 3 196 202 10.1016/j.autrev.2011.05.012 21619947
    [Google Scholar]
  220. Prud’homme G.J. Glinka Y. Wang Q. Immunological GABAergic interactions and therapeutic applications in autoimmune diseases. Autoimmun. Rev. 2015 14 11 1048 1056 10.1016/j.autrev.2015.07.011 26226414
    [Google Scholar]
  221. Bhat R. Axtell R. Mitra A. Miranda M. Lock C. Tsien R.W. Steinman L. Inhibitory role for GABA in autoimmune inflammation. Proc. Natl. Acad. Sci. USA 2010 107 6 2580 2585 10.1073/pnas.0915139107 20133656
    [Google Scholar]
  222. Polak P.E. Dull R.O. Kalinin S. Sharp A.J. Ripper R. Weinberg G. Schwartz D.E. Rubinstein I. Feinstein D.L. Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis. J. Neuroinflammation 2012 9 1 272 10.1186/1742‑2094‑9‑272 23253693
    [Google Scholar]
  223. Vansant G. Trauger R.J. Cameron A. Vendemelio M. Kreitschitz S. Carlo A.T. Banaszczyk M.G. Carlo D.J. Hendler S. Ill C.R. Propofol hemisuccinate suppression of experimental autoimmune encephalomyelitis. Autoimmunity 2007 40 3 180 186 10.1080/08916930701204467 17453716
    [Google Scholar]
  224. Andrews J.A. Jackson C.E. Heiman-Patterson T.D. Bettica P. Brooks B.R. Pioro E.P. Real-world evidence of riluzole effectiveness in treating amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Frontotemporal Degener. 2020 21 7-8 509 518 10.1080/21678421.2020.1771734 32573277
    [Google Scholar]
  225. Vernino S. McEvoy K. Propofol for stiff-person syndrome. Neurology 2008 70 18 1584 1585 10.1212/01.wnl.0000310971.62712.40 18443308
    [Google Scholar]
  226. Ledowski T. Russell P. Anaesthesia for stiff person syndrome: Successful use of total intravenous anaesthesia. Anaesthesia 2006 61 7 725 10.1111/j.1365‑2044.2006.04699.x 16792638
    [Google Scholar]
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