Mdivi-1 pretreatment mitigates isoflurane-induced cognitive deficits in developmental rats.

Mdivi-1 pretreatment mitigates isoflurane-induced cognitive deficits in developmental rats. Am J Transl Res. 2018;10(2):432-443 Authors: Gao J, Luo A, Yan J, Fang X, Tang X, Zhao Y, Li S Abstract Accumulating evidence indicates that general anesthetics can cause acute neuroapoptosis and long-term cognitive deficit in models exposed to anesthetics during the brain growth-spurt period. Anesthetics-induced imbalance of mitochondrial fusion and fission preceded and contributed to developmental neuroapoptosis. Accordingly, the imbalance was accompanied by activation of dynamin-related protein (Drp)1 which was closely associated with synaptic degeneration in neurodegenerative diseases. Based on the neuroprotective role of mitochondrial division inhibitor-1 (mdivi-1) in neurodegeneration and stroke, we set out to examine whether mdivi-1 can mitigate developmental neurotoxicity induced by isoflurane. In the present study, we showed that 2% isoflurane exposure for 2 h triggered Drp1 dephosphorylation at serine 656 and increased translocation of Drp1 and Bax from cytosol to mitochondria, concomitant with cytochrome C leakage into the cytosol. Remarkably, pretreatment with mdivi-1 not only alleviated isoflurane-induced disturbed mitochondrial translocation of Drp1 and Bax and almost restored morphological changes, but also inhibited cytochrome C release, caspase9 and caspase3 activation in hippocampi. Furthermore, mdivi-1 mitigated the loss of ...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research