Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage

Arend M. Hamming; Marieke J.H. Wermer; S. Umesh Rudrapatna; Christian Lanier; Hine J.A. Van Os; Walter M. Van Den Bergh; Michel D. Ferrari; Annette Van Der Toorn; Arn M.J.M. Van Den Maagdenberg; Ann M. Stowe; Rick M. Dijkhuizen

doi:10.1177/0271678X15619189

Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage

Arend M. Hamming, Marieke J.H. Wermer, S. Umesh Rudrapatna, Christian Lanier, Hine J.A. Van Os, Walter M. Van Den Bergh, Michel D. Ferrari, Annette Van Der Toorn, Arn M.J.M. Van Den Maagdenberg, Ann M. Stowe, Rick M. Dijkhuizen

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Spreading depolarizations may contribute to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, but the effect of spreading depolarizations on brain lesion progression after subarachnoid hemorrhage has not yet been assessed directly. Therefore, we tested the hypothesis that artificially induced spreading depolarizations increase brain tissue damage in a rat model of subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by endovascular puncture of the right internal carotid bifurcation. After one day, brain tissue damage was measured with T 2 -weighted MRI, followed by application of 1 M KCl (SD group, N = 16) or saline (no-SD group, N = 16) to the right cortex. Cortical laser-Doppler flowmetry was performed to record spreading depolarizations. MRI was repeated on day 3, after which brains were extracted for assessment of subarachnoid hemorrhage severity and histological damage. 5.0 ± 2.7 spreading depolarizations were recorded in the SD group. Subarachnoid hemorrhage severity and mortality were similar between the SD and no-SD groups. Subarachnoid hemorrhage-induced brain lesions expanded between days 1 and 3. This lesion growth was larger in the SD group (241 ± 233mm³) than in the no-SD group (29 ± 54mm³) (p = 0.001). We conclude that induction of spreading depolarizations significantly advances lesion growth after experimental subarachnoid hemorrhage. Our study underscores the pathophysiological consequence of spreading depolarizations in the development of delayed cerebral tissue injury after subarachnoid hemorrhage.

Original language	English
Pages (from-to)	1224-1231
Number of pages	8
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	36
Issue number	7
DOIs	https://doi.org/10.1177/0271678X15619189
State	Published - Jul 1 2016

Bibliographical note

Publisher Copyright:
© The Author(s) 2015.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dr Wermer was supported by personal grants from the Netherlands Organization for Scientific Research (ZonMW Veni grant), the Netherlands Heart Foundation (2011T055) and the Dutch Brain Foundation (project 2011(1)-102). This work was partly supported by the Utrecht University High Potential Program (R.M.D.) and the EU Marie Curie IAPP Program ''BRAINPATH'' (nr 612360) (A.M.J.M.v.d.M.) and the American Heart Association (A.M.S.).

Funders	Funder number
Dutch Brain Foundation	2011(1)-102
Netherlands Heart Foundation	2011T055
American the American Heart Association
European Commission	612360
European Commission
ZonMw Memorabel
Universiteit Utrecht
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Keywords

Subarachnoid hemorrhage
animal models
brain imaging
magnetic resonance
spreading depression

ASJC Scopus subject areas

Neurology
Clinical Neurology
Cardiology and Cardiovascular Medicine

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10.1177/0271678X15619189

Cite this

Hamming, A. M., Wermer, M. J. H., Umesh Rudrapatna, S., Lanier, C., Van Os, H. J. A., Van Den Bergh, W. M., Ferrari, M. D., Van Der Toorn, A., Van Den Maagdenberg, A. M. J. M., Stowe, A. M., & Dijkhuizen, R. M. (2016). Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage. Journal of Cerebral Blood Flow and Metabolism, 36(7), 1224-1231. https://doi.org/10.1177/0271678X15619189

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title = "Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage",

abstract = "Spreading depolarizations may contribute to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, but the effect of spreading depolarizations on brain lesion progression after subarachnoid hemorrhage has not yet been assessed directly. Therefore, we tested the hypothesis that artificially induced spreading depolarizations increase brain tissue damage in a rat model of subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by endovascular puncture of the right internal carotid bifurcation. After one day, brain tissue damage was measured with T 2 -weighted MRI, followed by application of 1 M KCl (SD group, N = 16) or saline (no-SD group, N = 16) to the right cortex. Cortical laser-Doppler flowmetry was performed to record spreading depolarizations. MRI was repeated on day 3, after which brains were extracted for assessment of subarachnoid hemorrhage severity and histological damage. 5.0 ± 2.7 spreading depolarizations were recorded in the SD group. Subarachnoid hemorrhage severity and mortality were similar between the SD and no-SD groups. Subarachnoid hemorrhage-induced brain lesions expanded between days 1 and 3. This lesion growth was larger in the SD group (241 ± 233mm3) than in the no-SD group (29 ± 54mm3) (p = 0.001). We conclude that induction of spreading depolarizations significantly advances lesion growth after experimental subarachnoid hemorrhage. Our study underscores the pathophysiological consequence of spreading depolarizations in the development of delayed cerebral tissue injury after subarachnoid hemorrhage.",

keywords = "Subarachnoid hemorrhage, animal models, brain imaging, magnetic resonance, spreading depression",

author = "Hamming, \{Arend M.\} and Wermer, \{Marieke J.H.\} and \{Umesh Rudrapatna\}, S. and Christian Lanier and \{Van Os\}, \{Hine J.A.\} and \{Van Den Bergh\}, \{Walter M.\} and Ferrari, \{Michel D.\} and \{Van Der Toorn\}, Annette and \{Van Den Maagdenberg\}, \{Arn M.J.M.\} and Stowe, \{Ann M.\} and Dijkhuizen, \{Rick M.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2015.",

year = "2016",

month = jul,

day = "1",

doi = "10.1177/0271678X15619189",

language = "English",

volume = "36",

pages = "1224--1231",

number = "7",

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Hamming, AM, Wermer, MJH, Umesh Rudrapatna, S, Lanier, C, Van Os, HJA, Van Den Bergh, WM, Ferrari, MD, Van Der Toorn, A, Van Den Maagdenberg, AMJM, Stowe, AM & Dijkhuizen, RM 2016, 'Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage', Journal of Cerebral Blood Flow and Metabolism, vol. 36, no. 7, pp. 1224-1231. https://doi.org/10.1177/0271678X15619189

TY - JOUR

T1 - Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage

AU - Hamming, Arend M.

AU - Wermer, Marieke J.H.

AU - Umesh Rudrapatna, S.

AU - Lanier, Christian

AU - Van Os, Hine J.A.

AU - Van Den Bergh, Walter M.

AU - Ferrari, Michel D.

AU - Van Der Toorn, Annette

AU - Van Den Maagdenberg, Arn M.J.M.

AU - Stowe, Ann M.

AU - Dijkhuizen, Rick M.

N1 - Publisher Copyright: © The Author(s) 2015.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Spreading depolarizations may contribute to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, but the effect of spreading depolarizations on brain lesion progression after subarachnoid hemorrhage has not yet been assessed directly. Therefore, we tested the hypothesis that artificially induced spreading depolarizations increase brain tissue damage in a rat model of subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by endovascular puncture of the right internal carotid bifurcation. After one day, brain tissue damage was measured with T 2 -weighted MRI, followed by application of 1 M KCl (SD group, N = 16) or saline (no-SD group, N = 16) to the right cortex. Cortical laser-Doppler flowmetry was performed to record spreading depolarizations. MRI was repeated on day 3, after which brains were extracted for assessment of subarachnoid hemorrhage severity and histological damage. 5.0 ± 2.7 spreading depolarizations were recorded in the SD group. Subarachnoid hemorrhage severity and mortality were similar between the SD and no-SD groups. Subarachnoid hemorrhage-induced brain lesions expanded between days 1 and 3. This lesion growth was larger in the SD group (241 ± 233mm3) than in the no-SD group (29 ± 54mm3) (p = 0.001). We conclude that induction of spreading depolarizations significantly advances lesion growth after experimental subarachnoid hemorrhage. Our study underscores the pathophysiological consequence of spreading depolarizations in the development of delayed cerebral tissue injury after subarachnoid hemorrhage.

AB - Spreading depolarizations may contribute to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, but the effect of spreading depolarizations on brain lesion progression after subarachnoid hemorrhage has not yet been assessed directly. Therefore, we tested the hypothesis that artificially induced spreading depolarizations increase brain tissue damage in a rat model of subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by endovascular puncture of the right internal carotid bifurcation. After one day, brain tissue damage was measured with T 2 -weighted MRI, followed by application of 1 M KCl (SD group, N = 16) or saline (no-SD group, N = 16) to the right cortex. Cortical laser-Doppler flowmetry was performed to record spreading depolarizations. MRI was repeated on day 3, after which brains were extracted for assessment of subarachnoid hemorrhage severity and histological damage. 5.0 ± 2.7 spreading depolarizations were recorded in the SD group. Subarachnoid hemorrhage severity and mortality were similar between the SD and no-SD groups. Subarachnoid hemorrhage-induced brain lesions expanded between days 1 and 3. This lesion growth was larger in the SD group (241 ± 233mm3) than in the no-SD group (29 ± 54mm3) (p = 0.001). We conclude that induction of spreading depolarizations significantly advances lesion growth after experimental subarachnoid hemorrhage. Our study underscores the pathophysiological consequence of spreading depolarizations in the development of delayed cerebral tissue injury after subarachnoid hemorrhage.

KW - Subarachnoid hemorrhage

KW - animal models

KW - brain imaging

KW - magnetic resonance

KW - spreading depression

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JO - Journal of Cerebral Blood Flow and Metabolism

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Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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