Progesterone treatment improves cognitive outcome following experimental traumatic brain injury in rats

Abstract

Progesterone (PROG) has recently been shown to have a neuroprotective effect and improve cognitive outcome in animal models of traumatic brain injury (TBI). However, the precise mechanisms remain unclear. This study was aimed to investigate the inhibitory effects of PROG on inflammation and apoptosis in the hippocampus after TBI and its influence on the cognitive outcome. In this study, the model of TBI was established by modified Feeney's weight-dropping method. The PROG was given in a dose of 16mg/kg by intraperitoneal injection 1h post injury and subsequent injections subcutaneously at 6h and 12h after TBI. Brain samples were extracted at 24h after trauma. The expression of COX-2 and caspase-3 was measured by immunohistochemistry and western blot technique. The cognitive outcome was assessed by Morris water maze test (MWM). The results revealed that the expression of COX-2 and caspase-3 in TBI-PROG group was distinctly less than those of the TBI group (p<0.05). In addition, the performance of Morris water maze showed that progesterone treatment exhibited shorter latencies, more platform crossings and more time swimming in the quadrant area in the TBI+PROG rats compared to the TBI rats. In conclusion, post-TBI PROG administration may attenuate inflammation and apoptosis in the hippocampus, and this may be one of the mechanisms by which PROG improves cognitive outcome following TBI.