Journal
STROKE
Volume 34, Issue 4, Pages 1015-1020Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.STR.0000063404.27912.5B
Keywords
brain ischemia; middle cerebral artery occlusion; mitochondria; potassium channels; rats
Categories
Funding
- NHLBI NIH HHS [HL46558, HL30260, HL50587] Funding Source: Medline
Ask authors/readers for more resources
Background and Purpose-The role of mitochondrial ATP-sensitive potassium channels (mitoK(ATP)) in ischemic tolerance has been well documented in heart, but little work has been done in brain. To investigate the involvement of mitoK(ATP) activation in chemical preconditioning in brain, we examined the effect of 5-hydroxydecanoate (5-HD), a selective mitoK(ATP) blocker, on neurotoxin 3-nitropropionic acid (3-NPA)-induced ischemic tolerance to transient focal cerebral ischemia in rats. Methods-Male Wistar rats were administrated 3-NPA (20 mg/kg IP; n=16) or vehicle (saline; n=16) 3 days before temporary occlusion (120 minutes) of the middle cerebral artery; 5-HD (40 mg/kg IP; n=16) was injected 20 minutes before 3-NPA administration. Infarct volumes were measured 4 days after reperfusion. To directly investigate whether chemical preconditioning activates mitoK(ATP), we tested the effect of prior incubation with 1 mmol/L 5-HD on 300 mumol/L 3-NPA -induced alterations of mitochondrial membrane potential (DeltaPsi(m)) in cultured neurons and astrocytes using the fluorescent dye tetramethylrhodamine ethyl ester. Results-Treatment with 3-NPA exhibited a 16% reduction (P<0.05) and 23% reduction in infarct volume (P<0.01) for total brain and cortex, respectively. Pretreatment with 5-HD completely abolished the neuroprotective effect of chemical preconditioning. In cultured cells, 3-NPA resulted in mitochondrial depolarization. This change of DeltaPsi(m) was completely blocked by 5-HD pretreatment. Conclusions-These results strongly suggest that opening of mitoK(ATP) plays a key role as the trigger in the development of 3-NPA-induced ischemic tolerance in brain.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available