Effect of sex steroid hormones on brain edema, intracranial pressure, and neurologic outcomes after traumatic brain injury

Can J Physiol Pharmacol. 2010 Apr;88(4):414-21. doi: 10.1139/y09-126.


Recent studies have reported that estrogen and progesterone have a neuroprotective effect after traumatic brain injury (TBI); however, the mechanism(s) for this effect have not yet been elucidated. The aim of the present study was to investigate the role of sex steroid hormones on changes in brain edema, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) after TBI in ovariectomized (OVX) rats. In this study, 50 female rats were divided into 5 groups: control (intact), sham, and 3 TBI groups consisting of vehicle, estrogen (1 mg/kg), and progesterone (8 mg/kg). TBI was induced by the Marmarou method, and the hormones were injected i.p. 30 min after TBI. ICP was measured in the spinal cord, and CPP was calculated by subtracting the mean arterial pressure (MAP) from ICP. The results revealed that brain water content after TBI was lower (p < 0.001) in the estrogen and progesterone groups than in the vehicle group. After trauma, ICP was significantly higher in TBI rats (p < 0.001). The ICP in the estrogen and progesterone groups decreased at 4 and 24 h after TBI compared with vehicle (p < 0.001 and p < 0.05, respectively). The CPP in the estrogen and progesterone groups increased after 24 h compared with vehicle (p < 0.001). Also after TBI, the neurological score (veterinary coma scale) was significantly higher than vehicle at 1 h (p < 0.01) and 24 h (p < 0.001) in the group treated with estrogen. In conclusion, pharmacological doses of estrogen and progesterone improved ICP, CPP, and neurological scores after TBI in OVX rats, which implies that these hormones play a neuroprotective role in TBI.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Edema / chemically induced
  • Brain Edema / drug therapy*
  • Brain Injuries / drug therapy*
  • Drug Evaluation, Preclinical
  • Estrogens / therapeutic use*
  • Female
  • Intracranial Pressure / drug effects*
  • Intracranial Pressure / physiology
  • Nervous System Diseases
  • Ovariectomy
  • Progesterone / therapeutic use*
  • Rats
  • Rats, Wistar
  • Treatment Outcome


  • Estrogens
  • Progesterone