Abstract:
AZMCAO) for 2h followed by varying time points of reperfusion. The brain loci specific and time dependent alterations were seen in the expression pattern of molecular markers i.e. heat-shock protein 70 (HSP70) for cytoplasmic dysfunction, glucose-regulated protein 78 (GRP78), Caspase-12, C/EBP homologous protein/growth arrest and DNA damage-inducible gene 153 (CHOP/GADD153), activating transcription factor 4 (ATF-4) and Processed X-box protein 1 (xbp1) mRNA for ER dysfunction. Histological examinations indicated pronounced brain damage, massive neuronal loss and DNA fragmentation predominantly in the striatum and cortex. The enhanced expression of GRP78, Caspase-12, CHOP/GADD153, ATF4 and processing of xbp1 mRNA in the affected brain loci indicate the critical involvement of ER mediated cell death/survival mechanisms and also collectively demonstrated the activation of UPR signaling pathways i.e. PERK and IRE1. Further, Salubrinal, a selective inhibitor of eIF2α dephosphorylation was used to counteract ER stress, which significantly increased the phosphorylation of eIF2α, leading to reduced brain damage after I/R injury. Therefore, inhibition of ER stress following I/R injury may be used as therapeutic target for neuroprotection.
