Cerebrovascular function and mitochondrial bioenergetics after ischemia-reperfusion in male rats

Area of Science:

• Cardiovascular Biology
• Mitochondrial Biology
• Cerebrovascular Research

Background:

• Ischemia/reperfusion (I/R) injury following transient middle cerebral artery occlusion (tMCAO) in male rats causes complex changes in mitochondrial proteins, mitochondrial DNA, and arterial dilation.
• The precise morphological and functional consequences of I/R on mitochondria within the middle cerebral arteries (MCAs) remain incompletely understood.

Purpose of the Study:

• To investigate the morphological and functional effects of I/R on mitochondria in MCAs.
• To assess changes in mitochondrial oxygen consumption rate (OCR) and Ca2+ sparks activity post-tMCAO.

Main Methods:

• Electron microscopy, Western blot, OCR measurements, and Ca2+ sparks activity assays were performed on MCAs from male Sprague Dawley rats (Naïve, tMCAO, Sham).
• Comparisons were made between ipsilateral (IPSI) and contralateral (CONTRA) MCAs, as well as with Sham and Naïve controls.

Main Results:

• Significantly increased OCR was observed in IPSI MCAs compared to CONTRA, Sham, and Naïve groups.
• Expression of Mitofusin-2 and OPA-1 was decreased in IPSI arteries, while mitochondrial morphology showed disruption in vascular smooth muscle but potentially increased numbers in IPSI vs. CONTRA MCAs.
• Baseline Ca2+ events were fewer in IPSI MCAs, and mitochondrial depolarization increased Ca2+ sparks activity in IPSI, Sham, and Naïve groups, but not CONTRA.

Conclusions:

• Ischemia/reperfusion induces significant alterations in mitochondrial structure and function within MCAs.
• These mitochondrial changes influence both oxygen consumption rates and Ca2+ sparks activity, with effects observed in both the directly affected (IPSI) and unaffected (CONTRA) arteries.