Neuroprotection Induced by N-acetylcysteine and Selenium Against Traumatic Brain Injury-Induced Apoptosis and Calcium Entry in Hippocampus of Rat

Neurodegeneration associated with acute central nervous system injuries and diseases such as spinal cord injury and traumatic brain injury (TBI) are reported to be mediated by the regulation of apoptosis and oxidative stress through Ca2+ influx. The thiol redox system antioxidants, such as N-acetylcysteine (NAC) and selenium (Se), display neuroprotective activities mediated at least in part by their antioxidant and anti-inflammatory properties. However, there are no reports on hippocampal apoptosis, cytosolic reactive oxygen species (ROS), or Ca2+ values in rats with an induced TBI. Therefore, we tested the effects of Se and NAC administration on apoptosis, oxidative stress, and Ca2+ influx through TRPV1 channel activations in the hippocampus of TBI-induced rats. The 32 rats were divided into four groups: control, TBI, TBI + NAC, and TBI + Se groups. Intraperitoneal administrations of NAC and Se were performed at 1, 24, 48, and 72 h after TBI induction. After 3 days, the hippocampal neurons were freshly isolated from the rats. In cytosolic-free Ca2+ analyses, the neurons were stimulated with the TRPV1 channel agonist capsaicin, a pungent compound found in hot chili peppers. Cytosolic-free Ca2+, apoptosis, cytosolic ROS levels, and caspase-3 and -9 activities were higher in the TBI group than control. The values in the hippocampus were decreased by Se and NAC administrations. In conclusion, we observed that NAC and Se have protective effects on oxidative stress, apoptosis, and Ca2+ entry via TRPV1 channel activation in the hippocampus of this TBI model, but the effect of NAC appears to be much greater than that of Se. They are both interesting candidates for studying the amelioration of TBIs. Possible molecular pathways of TBI on oxidative stress, apoptosis and Ca2+ entry through TRPV1 cation channels in hippocampus and DRG neurons. It is likely that TRPV1-mediated Ca2+ entry in the hippocampus of epileptic rats involves accumulation of ROS and opening of mitochondrial membrane pores that consequently leads to mitochondrial dysfunction, substantial swelling of the mitochondria with rupture of the outer membrane and release of apoptosis-inducing factors such as caspase-3 and -9.