Transient global cerebral ischemia differentially affects cortex, striatum and hippocampus in Bilateral Common Carotid Arterial occlusion (BCCAo) mouse model

Despite the advancements in medical sciences in last few decades, we are yet to develop promising therapeutics for stroke, which is one of the current global non-communicative disease concerns. The occurrence of stroke is likely to increase further due to the transition in our lifestyles. Inadequate knowledge of the sequential region-specific pathological events induced by cerebral ischemia is one of the underlying reasons. Hence to address this, we have used Bilateral Common Carotid Arterial occlusion (BCCAo) model that mimics human cardiac arrest condition. After ischemic insult, motor coordination and cognitive functions were analysed through series of behavioral tasks. Animals were sacrificed and brain regions viz. cortex, striatum and hippocampus, were isolated further for histopathology and molecular investigations. All the molecular studies were performed at 1d and 7d post-ischemia and reperfusion by immunohistochemistry, RT-qPCR and western blot analysis, for hypoxic, inflammatory and apoptotic markers. Our study indicates that unlike cortex and striatum, hippocampus was found to be consistently late ischemic susceptible at a behavioral and molecular level which might be regulated by c-Jun N-terminal kinases (JNK) and AKT signaling mechanism with associative changes in NMDA receptors. This study shows a region-specific temporal molecular response to global ischemia in the brain, which is important to get better insight into the pathophysiology since each region consists of different subsets of neurons that are having different susceptibility and tolerance pattern/level. This insight into a temporally different ischemic response and the underlying molecular basis might help in strategizing the effective therapeutics against stroke.