Studies on cross talk between innate immune response and mitochondrial dnamics following global ischemic injury

Abstract

The study demonstrates that innate immune response mediated by TLR4 and TNFR1 through NF-and#954;B-PGC-1and#945; pathway favors mitochondrial fission under hypoxic conditions in astrocytes. These findings were confirmed by using MG132, a proteasomal inhibitor, which reduced NF-and#954;B activation. Inhibition of NF-and#954;B activation after chronic hypoxic injury was found to be beneficial in restoring the mitochondrial fusion. In vivo studies on MG132 treatment restored ADP/ATP balance, synaptic integrity, histopathological and behavioral changes following BCCAO. These findings indicate that the strategies aimed at modulating innate immune response and mitochondrial dynamics might improve the outcomes associated with chronic hypoxic insult to the brain. newline