The Effects of MK-801 on Apoptosis in a Traumatic Brain Injury Model in Rat Pups

Abstract

Traumatic brain injury (TBI) is an essential cause of morbidity and mortality during childhood. Trauma causes some changes that result in delayed and elongated damage known as secondary injury, which is characterized by neuronal apoptosis. Based on this information, the aim of this study was to investigate the effect of MK-801, a competitive NMDA receptor antagonist, on apoptosis against hippocampal damage in rat pups after TBI. Forty-two, 10-day-old Wistar Albino rats were randomly divided into three groups: Control, a Trauma, and Treatment groups, each having fourteen rats. TBI was created by blunt trauma model. MK-801, was injected intraperitoneally at the doses of 1 mg/kg of body weight immediately after induction of TBI. The hippocampus tissues were harvested 4 days after TBI. Then CA1 and dentate gyrus (DG) regions were evaluated in terms of immunoreactivity with BAX, cytochrome C, and caspase 3. Based on this evaluation, the control group showed weakly BAX and Cytochrome C immunoreactivities in hippocampus, but elevated reactions were observed in TBI group. Especially, it was determined that the cytochrome c immunoreactivity was granular form in the neurons of hippocampus DG region. In the Treatment group decreased BAX and Cytochrome C immunoreactivities. While a weak caspase-3 immunoreactivity was observed in control group, stronger immunoreactivity was determined both DG and CA1 region of hippocampus in TBI group. In the Treatment group, caspase-3 immunoreactivity decreased in hippocampus region when compared to TBI group. Our results showed that treatment with MK-801 may significantly decreased apoptosis through BAX, Cytochrome C and caspase-3 pathway.