Addressing the alterations in cerebral ischemia-reperfusion injury on the brain mitochondrial activity: A possible link to cognitive decline

Studies suggest that different anatomical regions in a normal brain show distinct mitochondrial physiology. But the pathological role of mitochondria during ischemia-reperfusion injury (IRI) from these brain regions are yet to be addressed. The objective of this study is to identify mitochondrial perturbations from the brain regions of cortex and striatum, exposed to IRI and their correlation with cognition. A rat model of bilateral carotid artery occlusion was used to induce ischemia (15 min and 30 min) followed by reperfusion of varying time points (15 min, 30 min, 4 h and 24 h). It was evident from the results that ischemia (30 min) caused changes in cerebral histology which was aggravated upon reperfusion. Upon examining the mitochondria, ischemia significantly reduced the ETC enzyme activity (complex-I and II) and ATP level in the striatum. Reperfusion further aggravated this decline by 4 h. Following 24 h reperfusion, the functional activity of ETC recovered in the striatum but not in the cortex. The complex-I, II activity and ATP level significantly declined by 24 h reperfusion in the cortex. Cortical mitochondria showed significantly reduced antioxidant enzyme activities (catalase and GPx) by the end of 24 h reperfusion. The implication of cellular events was noted as a decline in the cortex related cognitive performance in radial arm maze and Morris water maze tests. The susceptibility of mitochondria to IRI is different across the brain regions (striatum > cortex). Hence the observed loss of mitochondrial energy metabolism might be a contributing factor for cognitive decline in IRI.