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Published on: December 28, 2014
Long-Term Region-Specific Mitochondrial Functionality Changes in Both Cerebral Hemispheres after fMCAo Model of
Ksenija Lūcija Bahire1, Reinis Maļuhins1, Fiona Bello1
1Department of Pharmacology, Faculty of Medicine, University of Latvia, LV-1586 Riga, Latvia.
Abstract:
Cerebral ischemia/reperfusion (I/R) refers to a secondary brain injury that results in mitochondrial dysfunction of variable extent, leading to neuronal cell damage. The impact of this process has mainly been studied in the short term, from the early hours up to one week after blood flow reperfusion, and in the ischemic hemisphere only. The focus of this study was to assess the long-term impacts of I/R on mitochondrial functionality using high-resolution fluorespirometry to evaluate state-dependent activities in both ischemic (ipsilateral) and non-ischemic (contralateral) hemispheres of male mice 60, 90, 120, and 180 days after I/R caused by 60-min-long filament-induced middle cerebral artery occlusion (fMCAo). Our results indicate that in cortical tissues, succinate-supported oxygen flux (Complex I&II OXPHOS state) and H2O2 production (Complex II LEAK state) were significantly decreased in the fMCAo (stroke) group ipsilateral hemisphere compared to measurements in the contralateral hemisphere 60 and 90 days after stroke. In hippocampal tissues, during the Complex I&II ET state, mitochondrial respiration was generally lower in the ipsilateral compared to the contralateral hemisphere 90 days following stroke. An aging-dependent impact on mitochondria oxygen consumption following I/R injury was observed 180 days after surgery, wherein Complex I&II activities were lowest in both hemispheres. The obtained results highlight the importance of long-term studies in the field of ischemic stroke, particularly when evaluating mitochondrial bioenergetics in specific brain regions within and between separately affected cerebral hemispheres.
Insights
Long-term cerebral ischemia/reperfusion (I/R) significantly impairs mitochondrial function in both hemispheres of the brain, with effects worsening with age. This study reveals lasting impacts on neuronal energy metabolism after stroke.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Ischemic Stroke Research
Background:
- Cerebral ischemia/reperfusion (I/R) causes secondary brain injury and mitochondrial dysfunction.
- Previous studies focused on short-term I/R effects, primarily in the affected hemisphere.
- Long-term consequences and bilateral impacts on mitochondrial function remain understudied.
Purpose of the Study:
- To investigate the long-term effects of I/R on mitochondrial functionality.
- To assess mitochondrial activities in both ischemic and non-ischemic brain hemispheres over extended periods.
- To evaluate age-dependent changes in mitochondrial bioenergetics post-stroke.
Main Methods:
- Filament-induced middle cerebral artery occlusion (fMCAo) in male mice to induce I/R.
- High-resolution fluorespirometry to measure mitochondrial state-dependent activities.
- Analysis of cortical and hippocampal tissues at 60, 90, 120, and 180 days post-I/R.
Main Results:
- Reduced Complex I&II OXPHOS and Complex II LEAK states in the ipsilateral hemisphere at 60 and 90 days.
- Lower mitochondrial respiration in the ipsilateral hippocampus during the Complex I&II ET state at 90 days.
- Age-dependent decline in Complex I&II activities observed in both hemispheres at 180 days.
Conclusions:
- Long-term mitochondrial dysfunction persists after cerebral I/R.
- I/R impacts mitochondrial bioenergetics in both ipsilateral and contralateral hemispheres.
- Aging exacerbates mitochondrial dysfunction following ischemic stroke, emphasizing the need for longitudinal studies.
