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Spreading depolarization and its influence on epileptiform activity.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Spreading depolarization and its influence on epileptiform activity.
Συγγραφείς: Lévesque M; Department of Neurology & Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Quebec, Canada., Köhling R; Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, Germany., Avoli M; Department of Neurology & Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Quebec, Canada.; Department of Physiology, McGill University, Quebec, Canada.
Πηγή: Epilepsia [Epilepsia] 2026 Mar; Vol. 67 (3), pp. 1078-1089. Date of Electronic Publication: 2025 Nov 08.
Τύπος έκδοσης: Journal Article; Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Blackwell Science Country of Publication: United States NLM ID: 2983306R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-1167 (Electronic) Linking ISSN: 00139580 NLM ISO Abbreviation: Epilepsia Subsets: MEDLINE
Imprint Name(s): Publication: Malden, MA : Blackwell Science
Original Publication: Copenhagen : Munskgaard
Ιατρικοί όροι (MeSH): Epilepsy*/physiopathology , Cortical Spreading Depression*/physiology , Cortical Spreading Depression*/drug effects, Neurons/physiology ; Humans ; Animals
Περίληψη: Spreading depolarization (SD) is a transient disruption of electrographic activity that slowly propagates through the gray matter by chemical contiguity, and it is characterized by a large depolarization of neurons and glial cells. SD, which is associated with massive changes in ion homeostasis, including extreme increases in [K+]o, was shown to occur in various neurological diseases such as migraine and traumatic brain injury. It is hypothesized to also occur in epilepsy. We review here the cellular and pharmacological features of SD that was mainly induced in vitro by different pharmacological manipulations as well as its relationship to focal seizures that can concomitantly occur in these in vitro and in vivo preparations. Recent experimental evidence points to SD playing a role in controlling seizure generation, but other studies have reported that SD facilitates ictogenesis. We conclude that further work is needed to firmly identify the role of SD in modulating focal seizure generation. These future experiments should also help in clearly defining the role played by SD in the manifestation of sudden unexpected death in epilepsy.
(© 2025 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
References: Neuroscience. 1978;3(11):1045-59. (PMID: 745780)
Nature. 1961 Sep 2;191:1010-1. (PMID: 13718947)
J Headache Pain. 2019 May 2;20(1):45. (PMID: 31046659)
Stroke. 2005 Jun;36(6):1270-7. (PMID: 15879337)
J Neurophysiol. 1956 Mar;19(2):154-71. (PMID: 13295838)
Front Cell Neurosci. 2022 Feb 10;16:837650. (PMID: 35237133)
J Physiol. 2012 Nov 15;590(22):5877-93. (PMID: 22907056)
Physiol Rev. 2001 Jul;81(3):1065-96. (PMID: 11427692)
J Comput Neurosci. 2012 Oct;33(2):207-25. (PMID: 22310969)
Nat Med. 2011 Apr;17(4):439-47. (PMID: 21475241)
Brain Res. 1977 Mar 4;123(1):113-24. (PMID: 843909)
Brain Res. 1982 Jun 10;241(2):329-33. (PMID: 7104715)
Neuron. 2009 Mar 26;61(6):820-38. (PMID: 19323993)
Nat Rev Neurol. 2013 Nov;9(11):637-44. (PMID: 24042483)
Brain Res. 1996 Oct 7;735(2):188-96. (PMID: 8911657)
J Cereb Blood Flow Metab. 1992 Mar;12(2):223-9. (PMID: 1312539)
Cereb Cortex. 2015 Nov;25(11):4469-76. (PMID: 25840424)
Exp Neurol. 2014 Mar;253:1-15. (PMID: 24368193)
J Neurophysiol. 1999 Nov;82(5):2590-601. (PMID: 10561429)
Neuroscience. 1993 Jul;55(1):57-68. (PMID: 8102481)
J Neurophysiol. 1990 Feb;63(2):225-39. (PMID: 2313342)
Nat Commun. 2021 Apr 13;12(1):2206. (PMID: 33850125)
J Cereb Blood Flow Metab. 2011 Jan;31(1):17-35. (PMID: 21045864)
J Neurophysiol. 1987 Mar;57(3):869-88. (PMID: 3031235)
Brain Res. 2003 Jun 13;975(1-2):129-34. (PMID: 12763600)
Am J Hum Genet. 2001 Jun;68(6):1327-32. (PMID: 11359211)
Brain. 2019 Feb 1;142(2):412-425. (PMID: 30649209)
J Neurochem. 1959 Feb;3(4):300-15. (PMID: 13642064)
Brain. 2012 Jan;135(Pt 1):259-75. (PMID: 22120143)
Neurobiol Dis. 2025 Jul;211:106937. (PMID: 40348201)
J Neurophysiol. 1990 Dec;64(6):1747-57. (PMID: 2074462)
J Cereb Blood Flow Metab. 2013 Oct;33(10):1582-94. (PMID: 23820646)
Brain Res. 1988 Aug 9;457(2):226-40. (PMID: 2851364)
J Neurophysiol. 2000 Jun;83(6):3519-24. (PMID: 10848567)
J Neurosci. 1994 Nov;14(11 Pt 2):7087-98. (PMID: 7965100)
J Neurosci. 1996 Jul 1;16(13):4113-28. (PMID: 8753873)
Exp Neurol. 2015 May;267:243-53. (PMID: 25819105)
J Neurophysiol. 1947 Nov;10(6):409-14. (PMID: 20268874)
Sci Transl Med. 2025 Sep 17;17(816):eadv3260. (PMID: 40961224)
Cereb Cortex. 2019 Mar 1;29(3):1150-1161. (PMID: 29425263)
Brain Res Dev Brain Res. 1989 Apr 1;46(2):243-52. (PMID: 2720957)
J Neurophysiol. 1988 Feb;59(2):450-67. (PMID: 3351570)
Naunyn Schmiedebergs Arch Pharmacol. 1998 Mar;357(3):225-31. (PMID: 9550292)
Brain Res. 1977 Jan 21;120(2):231-49. (PMID: 832122)
Exp Brain Res. 1977 Mar 30;27(3-4):237-43. (PMID: 880984)
Prog Neurobiol. 2018 Mar;162:1-16. (PMID: 29197650)
J Neurophysiol. 2006 Jun;95(6):3948-54. (PMID: 16554499)
Electroencephalogr Clin Neurophysiol. 1987 Apr;66(4):440-7. (PMID: 2435524)
Neurobiol Dis. 2023 May;180:106097. (PMID: 36967064)
Front Neurol. 2018 Feb 01;9:19. (PMID: 29449828)
Sci Rep. 2018 Nov 16;8(1):16959. (PMID: 30446731)
Epilepsia. 2019 Dec;60(12):2386-2397. (PMID: 31755112)
Neuroscience. 2020 Aug 10;441:176-183. (PMID: 32450296)
J Neurophysiol. 1995 Aug;74(2):565-73. (PMID: 7472364)
Exp Neurol. 1976 Oct;53(1):12-20. (PMID: 964333)
Nat Genet. 2000 Apr;24(4):343-5. (PMID: 10742094)
Brain Res. 1993 Apr 9;608(1):107-14. (PMID: 8495335)
Acta Physiol Scand. 1980 Apr;108(4):355-65. (PMID: 7415848)
Neurobiol Dis. 2020 Nov;145:105071. (PMID: 32890774)
Stroke. 2011 Oct;42(10):2917-22. (PMID: 21836085)
Brain Res. 1972 Apr 14;39(1):255-9. (PMID: 5025649)
J Neurosci. 2002 Dec 1;22(23):10106-15. (PMID: 12451111)
J Neurophysiol. 1995 Feb;73(2):468-84. (PMID: 7760112)
Acta Physiol Scand. 1981 Dec;113(4):437-45. (PMID: 7348028)
J Neurophysiol. 1985 Apr;53(4):1098-108. (PMID: 3998794)
J Neurophysiol. 1983 Mar;49(3):831-50. (PMID: 6834101)
Sci Transl Med. 2015 Apr 8;7(282):282ra46. (PMID: 25855492)
Nature. 1988 Nov 24;336(6197):379-81. (PMID: 3194020)
J Physiol. 1996 Jun 15;493 ( Pt 3):707-17. (PMID: 8799893)
Grant Information: Savoy Foundation; MOP130328 Canada CAPMC CIHR; PJT153310 Canada CAPMC CIHR; PJT166178 Canada CAPMC CIHR
Contributed Indexing: Keywords: ictogenesis; seizures; spreading depolarization; sudden unexpected death in epilepsy
Entry Date(s): Date Created: 20251108 Date Completed: 20260323 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC13007837
DOI: 10.1111/epi.70010
PMID: 41204888
Βάση Δεδομένων: MEDLINE
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  Data: Spreading depolarization and its influence on epileptiform activity.
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  Data: <searchLink fieldCode="AU" term="%22Lévesque+M%22">Lévesque M</searchLink>; Department of Neurology & Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Quebec, Canada.<br /><searchLink fieldCode="AU" term="%22Köhling+R%22">Köhling R</searchLink>; Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, Germany.<br /><searchLink fieldCode="AU" term="%22Avoli+M%22">Avoli M</searchLink>; Department of Neurology & Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Quebec, Canada.; Department of Physiology, McGill University, Quebec, Canada.
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  Data: <searchLink fieldCode="JN" term="%222983306R%22">Epilepsia</searchLink> [Epilepsia] 2026 Mar; Vol. 67 (3), pp. 1078-1089. <i>Date of Electronic Publication: </i>2025 Nov 08.
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  Label: Abstract
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  Data: Spreading depolarization (SD) is a transient disruption of electrographic activity that slowly propagates through the gray matter by chemical contiguity, and it is characterized by a large depolarization of neurons and glial cells. SD, which is associated with massive changes in ion homeostasis, including extreme increases in [K<superscript>+</superscript>]<subscript>o</subscript>, was shown to occur in various neurological diseases such as migraine and traumatic brain injury. It is hypothesized to also occur in epilepsy. We review here the cellular and pharmacological features of SD that was mainly induced in vitro by different pharmacological manipulations as well as its relationship to focal seizures that can concomitantly occur in these in vitro and in vivo preparations. Recent experimental evidence points to SD playing a role in controlling seizure generation, but other studies have reported that SD facilitates ictogenesis. We conclude that further work is needed to firmly identify the role of SD in modulating focal seizure generation. These future experiments should also help in clearly defining the role played by SD in the manifestation of sudden unexpected death in epilepsy.<br /> (© 2025 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
– Name: Ref
  Label: References
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  Data: Neuroscience. 1978;3(11):1045-59. (PMID: <searchLink fieldCode="PM" term="%22745780%22">745780)</searchLink><br />Nature. 1961 Sep 2;191:1010-1. (PMID: <searchLink fieldCode="PM" term="%2213718947%22">13718947)</searchLink><br />J Headache Pain. 2019 May 2;20(1):45. (PMID: <searchLink fieldCode="PM" term="%2231046659%22">31046659)</searchLink><br />Stroke. 2005 Jun;36(6):1270-7. (PMID: <searchLink fieldCode="PM" term="%2215879337%22">15879337)</searchLink><br />J Neurophysiol. 1956 Mar;19(2):154-71. (PMID: <searchLink fieldCode="PM" term="%2213295838%22">13295838)</searchLink><br />Front Cell Neurosci. 2022 Feb 10;16:837650. (PMID: <searchLink fieldCode="PM" term="%2235237133%22">35237133)</searchLink><br />J Physiol. 2012 Nov 15;590(22):5877-93. (PMID: <searchLink fieldCode="PM" term="%2222907056%22">22907056)</searchLink><br />Physiol Rev. 2001 Jul;81(3):1065-96. (PMID: <searchLink fieldCode="PM" term="%2211427692%22">11427692)</searchLink><br />J Comput Neurosci. 2012 Oct;33(2):207-25. (PMID: <searchLink fieldCode="PM" term="%2222310969%22">22310969)</searchLink><br />Nat Med. 2011 Apr;17(4):439-47. (PMID: <searchLink fieldCode="PM" term="%2221475241%22">21475241)</searchLink><br />Brain Res. 1977 Mar 4;123(1):113-24. (PMID: <searchLink fieldCode="PM" term="%22843909%22">843909)</searchLink><br />Brain Res. 1982 Jun 10;241(2):329-33. (PMID: <searchLink fieldCode="PM" term="%227104715%22">7104715)</searchLink><br />Neuron. 2009 Mar 26;61(6):820-38. (PMID: <searchLink fieldCode="PM" term="%2219323993%22">19323993)</searchLink><br />Nat Rev Neurol. 2013 Nov;9(11):637-44. (PMID: <searchLink fieldCode="PM" term="%2224042483%22">24042483)</searchLink><br />Brain Res. 1996 Oct 7;735(2):188-96. (PMID: <searchLink fieldCode="PM" term="%228911657%22">8911657)</searchLink><br />J Cereb Blood Flow Metab. 1992 Mar;12(2):223-9. (PMID: <searchLink fieldCode="PM" term="%221312539%22">1312539)</searchLink><br />Cereb Cortex. 2015 Nov;25(11):4469-76. (PMID: <searchLink fieldCode="PM" term="%2225840424%22">25840424)</searchLink><br />Exp Neurol. 2014 Mar;253:1-15. (PMID: <searchLink fieldCode="PM" term="%2224368193%22">24368193)</searchLink><br />J Neurophysiol. 1999 Nov;82(5):2590-601. (PMID: <searchLink fieldCode="PM" term="%2210561429%22">10561429)</searchLink><br />Neuroscience. 1993 Jul;55(1):57-68. (PMID: <searchLink fieldCode="PM" term="%228102481%22">8102481)</searchLink><br />J Neurophysiol. 1990 Feb;63(2):225-39. (PMID: <searchLink fieldCode="PM" term="%222313342%22">2313342)</searchLink><br />Nat Commun. 2021 Apr 13;12(1):2206. (PMID: <searchLink fieldCode="PM" term="%2233850125%22">33850125)</searchLink><br />J Cereb Blood Flow Metab. 2011 Jan;31(1):17-35. (PMID: <searchLink fieldCode="PM" term="%2221045864%22">21045864)</searchLink><br />J Neurophysiol. 1987 Mar;57(3):869-88. (PMID: <searchLink fieldCode="PM" term="%223031235%22">3031235)</searchLink><br />Brain Res. 2003 Jun 13;975(1-2):129-34. (PMID: <searchLink fieldCode="PM" term="%2212763600%22">12763600)</searchLink><br />Am J Hum Genet. 2001 Jun;68(6):1327-32. (PMID: <searchLink fieldCode="PM" term="%2211359211%22">11359211)</searchLink><br />Brain. 2019 Feb 1;142(2):412-425. (PMID: <searchLink fieldCode="PM" term="%2230649209%22">30649209)</searchLink><br />J Neurochem. 1959 Feb;3(4):300-15. (PMID: <searchLink fieldCode="PM" term="%2213642064%22">13642064)</searchLink><br />Brain. 2012 Jan;135(Pt 1):259-75. (PMID: <searchLink fieldCode="PM" term="%2222120143%22">22120143)</searchLink><br />Neurobiol Dis. 2025 Jul;211:106937. (PMID: <searchLink fieldCode="PM" term="%2240348201%22">40348201)</searchLink><br />J Neurophysiol. 1990 Dec;64(6):1747-57. (PMID: <searchLink fieldCode="PM" term="%222074462%22">2074462)</searchLink><br />J Cereb Blood Flow Metab. 2013 Oct;33(10):1582-94. (PMID: <searchLink fieldCode="PM" term="%2223820646%22">23820646)</searchLink><br />Brain Res. 1988 Aug 9;457(2):226-40. (PMID: <searchLink fieldCode="PM" term="%222851364%22">2851364)</searchLink><br />J Neurophysiol. 2000 Jun;83(6):3519-24. (PMID: <searchLink fieldCode="PM" term="%2210848567%22">10848567)</searchLink><br />J Neurosci. 1994 Nov;14(11 Pt 2):7087-98. (PMID: <searchLink fieldCode="PM" term="%227965100%22">7965100)</searchLink><br />J Neurosci. 1996 Jul 1;16(13):4113-28. (PMID: <searchLink fieldCode="PM" term="%228753873%22">8753873)</searchLink><br />Exp Neurol. 2015 May;267:243-53. (PMID: <searchLink fieldCode="PM" term="%2225819105%22">25819105)</searchLink><br />J Neurophysiol. 1947 Nov;10(6):409-14. (PMID: <searchLink fieldCode="PM" term="%2220268874%22">20268874)</searchLink><br />Sci Transl Med. 2025 Sep 17;17(816):eadv3260. (PMID: <searchLink fieldCode="PM" term="%2240961224%22">40961224)</searchLink><br />Cereb Cortex. 2019 Mar 1;29(3):1150-1161. (PMID: <searchLink fieldCode="PM" term="%2229425263%22">29425263)</searchLink><br />Brain Res Dev Brain Res. 1989 Apr 1;46(2):243-52. (PMID: <searchLink fieldCode="PM" term="%222720957%22">2720957)</searchLink><br />J Neurophysiol. 1988 Feb;59(2):450-67. (PMID: <searchLink fieldCode="PM" term="%223351570%22">3351570)</searchLink><br />Naunyn Schmiedebergs Arch Pharmacol. 1998 Mar;357(3):225-31. (PMID: <searchLink fieldCode="PM" term="%229550292%22">9550292)</searchLink><br />Brain Res. 1977 Jan 21;120(2):231-49. (PMID: <searchLink fieldCode="PM" term="%22832122%22">832122)</searchLink><br />Exp Brain Res. 1977 Mar 30;27(3-4):237-43. (PMID: <searchLink fieldCode="PM" term="%22880984%22">880984)</searchLink><br />Prog Neurobiol. 2018 Mar;162:1-16. (PMID: <searchLink fieldCode="PM" term="%2229197650%22">29197650)</searchLink><br />J Neurophysiol. 2006 Jun;95(6):3948-54. (PMID: <searchLink fieldCode="PM" term="%2216554499%22">16554499)</searchLink><br />Electroencephalogr Clin Neurophysiol. 1987 Apr;66(4):440-7. (PMID: <searchLink fieldCode="PM" term="%222435524%22">2435524)</searchLink><br />Neurobiol Dis. 2023 May;180:106097. (PMID: <searchLink fieldCode="PM" term="%2236967064%22">36967064)</searchLink><br />Front Neurol. 2018 Feb 01;9:19. (PMID: <searchLink fieldCode="PM" term="%2229449828%22">29449828)</searchLink><br />Sci Rep. 2018 Nov 16;8(1):16959. (PMID: <searchLink fieldCode="PM" term="%2230446731%22">30446731)</searchLink><br />Epilepsia. 2019 Dec;60(12):2386-2397. (PMID: <searchLink fieldCode="PM" term="%2231755112%22">31755112)</searchLink><br />Neuroscience. 2020 Aug 10;441:176-183. (PMID: <searchLink fieldCode="PM" term="%2232450296%22">32450296)</searchLink><br />J Neurophysiol. 1995 Aug;74(2):565-73. (PMID: <searchLink fieldCode="PM" term="%227472364%22">7472364)</searchLink><br />Exp Neurol. 1976 Oct;53(1):12-20. (PMID: <searchLink fieldCode="PM" term="%22964333%22">964333)</searchLink><br />Nat Genet. 2000 Apr;24(4):343-5. (PMID: <searchLink fieldCode="PM" term="%2210742094%22">10742094)</searchLink><br />Brain Res. 1993 Apr 9;608(1):107-14. (PMID: <searchLink fieldCode="PM" term="%228495335%22">8495335)</searchLink><br />Acta Physiol Scand. 1980 Apr;108(4):355-65. (PMID: <searchLink fieldCode="PM" term="%227415848%22">7415848)</searchLink><br />Neurobiol Dis. 2020 Nov;145:105071. (PMID: <searchLink fieldCode="PM" term="%2232890774%22">32890774)</searchLink><br />Stroke. 2011 Oct;42(10):2917-22. (PMID: <searchLink fieldCode="PM" term="%2221836085%22">21836085)</searchLink><br />Brain Res. 1972 Apr 14;39(1):255-9. (PMID: <searchLink fieldCode="PM" term="%225025649%22">5025649)</searchLink><br />J Neurosci. 2002 Dec 1;22(23):10106-15. (PMID: <searchLink fieldCode="PM" term="%2212451111%22">12451111)</searchLink><br />J Neurophysiol. 1995 Feb;73(2):468-84. (PMID: <searchLink fieldCode="PM" term="%227760112%22">7760112)</searchLink><br />Acta Physiol Scand. 1981 Dec;113(4):437-45. (PMID: <searchLink fieldCode="PM" term="%227348028%22">7348028)</searchLink><br />J Neurophysiol. 1985 Apr;53(4):1098-108. (PMID: <searchLink fieldCode="PM" term="%223998794%22">3998794)</searchLink><br />J Neurophysiol. 1983 Mar;49(3):831-50. (PMID: <searchLink fieldCode="PM" term="%226834101%22">6834101)</searchLink><br />Sci Transl Med. 2015 Apr 8;7(282):282ra46. (PMID: <searchLink fieldCode="PM" term="%2225855492%22">25855492)</searchLink><br />Nature. 1988 Nov 24;336(6197):379-81. (PMID: <searchLink fieldCode="PM" term="%223194020%22">3194020)</searchLink><br />J Physiol. 1996 Jun 15;493 ( Pt 3):707-17. (PMID: <searchLink fieldCode="PM" term="%228799893%22">8799893)</searchLink>
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  Data: Savoy Foundation; MOP130328 Canada CAPMC CIHR; PJT153310 Canada CAPMC CIHR; PJT166178 Canada CAPMC CIHR
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  Data: <i>Keywords: </i>ictogenesis; seizures; spreading depolarization; sudden unexpected death in epilepsy
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        Value: 10.1111/epi.70010
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        Text: English
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        StartPage: 1078
    Subjects:
      – SubjectFull: Neurons physiology
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Epilepsy physiopathology
        Type: general
      – SubjectFull: Cortical Spreading Depression physiology
        Type: general
      – SubjectFull: Cortical Spreading Depression drug effects
        Type: general
    Titles:
      – TitleFull: Spreading depolarization and its influence on epileptiform activity.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Lévesque M
      – PersonEntity:
          Name:
            NameFull: Köhling R
      – PersonEntity:
          Name:
            NameFull: Avoli M
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 03
              Text: 2026 Mar
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1528-1167
          Numbering:
            – Type: volume
              Value: 67
            – Type: issue
              Value: 3
          Titles:
            – TitleFull: Epilepsia
              Type: main
ResultId 1