Leptin Attenuate Brain Cellular Apoptosis After Traumatic Brain Injury In Rats

Objective:To study on the anti-apoptotic effect of leptin after traumatic brain injury in ratsMethods:Adult male SD rats (n=135) were randomly divided into 5 groups:Sham group; Sham+leptin group; TBI group; TBI+leptin(L) (5mg/kg) group; TBI+leptin(H) (10mg/kg) group. TBI groups subjected experimental TBI by Feeney’s modelling. All animals were euthanized at 24h post-surgery. The behavioral outcomes were assessed before euthanized. Neuronal activity was evaluated by Nissl staining and neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling (TUNEL). The expression of cleaved caspase3 was measured by immunohistochemistry (IHC) and Western blot. We also measured the expression of cytochrome C (CytoC), Bcl-2 and Bax within and without mitochondria by Western blot.Results:At 24 h after TBI. Leptin could improve neuronal survival. The number of TUNEL-positive stained cells within cortex was imcreased showed apoptosis was aggravated after TBI. And a significant increase of cleaved caspase3 which was accepted as a major factor of apoptosis was detected by Western blot and IHC. Leptin could markedly modify this damage.Both the expression of Bcl-2 and Bax intra-mitochondria increased after TBI. However, protein level of Bax extra-mitochondria reduced obviously, but protein level of Bcl-2 extra-mitochondria still increased. After treatment with leptin, expression of Bax and Bcl-2 intra-mitochondria was decreased and expression of these two proteins extra-mitochondria was increased obviously, especially in the high dose leptin treatment.Conclusion:Leptin could reduce neurological deficit scores and alleviate apoptotic impairment in TBI rats. This beneficial effect might induced through altering the permeability of mitochondria and decreasing CytoC release.