IMMP2L gene mutation activates mitochondrial apoptotic pathway to aggravate cerebral ischemic injury in mice

Objective To investigate the effect of inner mitochondrial membrane peptidase 2-like (IMMP2L) gene mutation on cerebral ischemic injury and its mechanism. Methods The cerebral ischemia/reperfusion (I/R) model was established in wild-type (WT) mice and mice with IMMP2L gene mutation (IMMP2L+/-) by middle cerebral artery occlusion (MCAO), and cortical tissues were collected at 0, 1, 5 and 24 hours after reperfusion. Laser speckle contrast imaging (LSCI) was used to monitor the change in cerebral blood flow (CBF). Longa behavioral score was used to evaluate neurological function. triphenyltetrazolium chloride (TTC), HE staining was used to evaluate cerebral infarction and neuron injury, TUNEL was used to evaluate the neuronal apoptosis. The protein expression of cleaved caspase-3 and apoptosis-inducing factor (AIF)was analyzed by Western blotting. The changes of cerebral blood flow (CBF) were monitored by laser speckle contrast imaging (LSCI), neurological function was evaluated by longa behavioral score, and cerebral infarction area and neuronal injury were observed by TTC staining and HE staining respectively; the changes of neuronal apoptosis were analyzed by TUNEL, and the protein expressions of cleaved caspase-3 (c-caspase-3) and apoptosis inducing factor (AIF) were detected by Western blotting. Results The neurobehavioral score was significantly higher in the IMMP2L+/- versus WT mice. The volume of the infarcted region, the number of degenerated neurons, and the degree of cerebral edema all increased at 5 and 24 hours after reperfusion. The apoptotic neurons increased at 0, 1, 5 and 24 hours after reperfusion and the protein levels of c-caspase-3 and AIF were up-regulated at 5 and 24 hours after I/R. Conclusion IMMP2L mutation aggravates cerebral ischemic injury by activating the mitochondrial apoptosis pathway.