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

Neurosci Lett. 2013 Oct 11:553:18-23. doi: 10.1016/j.neulet.2013.07.052. Epub 2013 Aug 14.

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 16 mg/kg by intraperitoneal injection 1h post injury and subsequent injections subcutaneously at 6h and 12 h after TBI. Brain samples were extracted at 24 h 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.

Keywords: Apoptosis; Cognitive function; Inflammation; Progesterone; Traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries / drug therapy*
  • Brain Injuries / pathology
  • Brain Injuries / psychology
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / enzymology
  • CA1 Region, Hippocampal / pathology
  • Caspase 3 / metabolism
  • Cognition / drug effects*
  • Cyclooxygenase 2 / metabolism
  • Inflammation / drug therapy
  • Inflammation / enzymology
  • Inflammation / pathology
  • Male
  • Maze Learning / drug effects
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Progesterone / pharmacology*
  • Progesterone / therapeutic use
  • Rats, Sprague-Dawley
  • Reaction Time

Substances

  • Neuroprotective Agents
  • Progesterone
  • Cyclooxygenase 2
  • Caspase 3