Abstract
We determined how experimental stroke affects mitochondrial oxygen consumption rate (OCR) in rat middle cerebral arteries (MCAs). Eight to ten week old male Sprague-Dawley rats were exposed to 90 min of ischemia by middle cerebral artery occlusion and 48 h reperfusion. The mitochondrial OCR of ischemic (IPSI) and non-ischemic (CONTRA) MCAs was investigated using the Seahorse XFe24 analyzer under basal conditions and after pharmacological challenge using diazoxide, one of the mitochondrial ATP sensitive potassium channel openers. Non-mitochondrial respiration (46 ± 4 pM/min/μg protein) as well as the components of mitochondrial respiration were significantly (p < 0.05) elevated in IPSI MCAs including: basal respiration (179 ±15 pM/min/μg protein), ATP production (66 ± 7 pM/min/μg protein), proton leak (113 ± 13 pM/min/μg protein), and maximal respiration (291 ± 20 pM/min/μg protein) compared with CONTRA values (128 ± 15 pM/min/μg, 49 ± 6 pM/min/μg, 68 ±10 pM/min/μg, 238 ± 23 pM/min/μg, and 31 ± 3 pM/min/μg protein, respectively) suggesting retained mitochondrial function in the IPSI MCAs. Acute treatment with diazoxide had little effect on mitochondrial respiration of IPSI arteries, but increased non-mitochondrial respiration (43 ± 4 pM/min/μg) and proton leak (98 ± 15 pM/min/μg protein) in CONTRA MCAs to IPSI levels. Our data provide direct evidence that substantial differences exist in the mitochondrial respiratory dynamics between previously ischemic and non-ischemic cerebral arteries and indicate the need for specific therapies directed toward each population of arteries in stroke patients following delayed tPA therapy. This work was supported by NIH grants HL-077731, HL-030260, HL-065380, and HL-093554.
Published Version
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