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Vasoconstrictive Neurovascular Coupling during Focal Ischemic Depolarizations

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Shin, Hwa Kyoung, Dunn, Andrew K, Jones, Phillip B, Boas, David A, Moskowitz, Michael A, Ayata, Cenk·2006·Journal of Cerebral Blood Flow & Metabolism
DOI 10.1038/sj.jcbfm.9600252
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Abstract

Ischemic depolarizing events, such as repetitive spontaneous periinfarct spreading depolarizations (PIDs), expand the infarct size after experimental middle cerebral artery (MCA) occlusion. This worsening may result from increased metabolic demand, exacerbating the mismatch between cerebral blood flow (CBF) and metabolism. Here, we present data showing that anoxic depolarization (AD) and PIDs caused vasoconstriction and abruptly reduced CBF in the ischemic cortex in a distal MCA occlusion model in mice. This reduction in CBF during AD increased the area of cortex with 20% or less residual CBF by 140%. With each subsequent PID, this area expanded by an additional 19%. Drugs that are known to inhibit cortical spreading depression (CSD), such as N-methyl-D-aspartate receptor antagonists MK-801 and 7-chlorokynurenic acid, and σ-1 receptor agonists dextromethorphan and carbetapentane, did not reduce the frequency of PIDs, but did diminish the severity of episodic hypoperfusions, and prevented the expansion of severely hypoperfused cortex, thus improving CBF during 90 mins of acute focal ischemia. In contrast, AMPA receptor antagonist NBQX, which does not inhibit CSD, did not impact the deterioration in CBF. When measured 24 h after distal MCA occlusion, infarct size was reduced by MK-801, but not by NBQX. Our results suggest that AD and PIDs expand the CBF deficit, and by so doing negatively impact lesion development in ischemic mouse brain. Mitigating the vasoconstrictive neurovascular coupling during intense ischemic depolarizations may provide a novel hemodynamic mechanism of neuroprotection by inhibitors of CSD.

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Cited by

Metadata

Authors
Shin, H. K., Dunn, A. K., Jones, P. B., Boas, D. A., Moskowitz, M. A., & Ayata, C.
Venue
Journal of Cerebral Blood Flow & Metabolism
Publisher
SAGE Publications
Published
2006-08
Volume
26
Issue
8
Pages
1018-1030
ISSN
  • 0271-678X (ISSN-L)
  • 1559-7016
DOI
10.1038/sj.jcbfm.9600252
OpenAlex
W2117340226
Cited by
320
References
1
FWCI
8.27
Type
journal article
Language
en
Open access
bronze
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)

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