期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 31, 期 7, 页码 1588-1598出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2011.28
关键词
cerebral blood flow; migraine; mitochondria; spreading depression; traumatic brain injury
资金
- Lundbeck Foundation via the Lundbeck Foundation Centre for Neurovascular Signalling (LU-CENS)
- NOVO Nordisk Foundation
- Danish Medical Research Council
- NORDEA foundation for Center for Healthy Aging
- Foundation Leducq
Cortical spreading depression (CSD) is associated with mitochondrial depolarization, increasing intracellular Ca2+, and the release of free fatty acids, which favor opening of the mitochondrial permeability transition pore (mPTP) and activation of calcineurin (CaN). Here, we test the hypothesis that cyclosporine A (CsA), which blocks both mPTP and CaN, ameliorates the persistent reduction of cerebral blood flow (CBF), impaired vascular reactivity, and a persistent rise in the cerebral metabolic rate of oxygen (CMRO2) following CSD. In addition to CsA, we used the specific mPTP blocker NIM811 and the specific CaN blocker FK506. Cortical spreading depression was induced in rat frontal cortex. Electrocortical activity was recorded by glass microelectrodes, CBF by laser Doppler flowmetry, and tissue oxygen tension with polarographic microelectrodes. Electrocortical activity, basal CBF, CMRO2, and neurovascular and neurometabolic coupling were unaffected by all three drugs under control conditions. NIM811 augmented the rise in CBF observed during CSD. Cyclosporine A and FK506 ameliorated the persistent decrease in CBF after CSD. All three drugs prevented disruption of neurovascular coupling after CSD; the rise in CMRO2 was unchanged. Our data suggest that blockade of mPTP formation and CaN activation may prevent persistent CBF reduction and vascular dysfunction after CSD. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1588-1598; doi: 10.1038/jcbfm.2011.28; published online 23 March 2011
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