Effect of atorvastatin on spatial memory, neuronal survival, and vascular density in female rats after traumatic brain injury

J Neurosurg. 2005 Oct;103(4):695-701. doi: 10.3171/jns.2005.103.4.0695.

Abstract

Object: Atorvastatin administered after traumatic brain injury (TBI) induced by controlled cortical impact promotes functional improvement in male rats. Note, however, that parallel studies have not been performed in female rats. Therefore, the authors tested the effect of atorvastatin on TBI in female rats.

Methods: Atorvastatin (1 mg/kg/day) was orally administered for 7 consecutive days in female Wistar rats starting I day after TBI; control animals received saline. Modified neurological severity scores, the corner turn test, and the Morris water maze test were used to evaluate functional response to treatment. Rats were killed on Day 15 post-TBI, and brain tissue samples were processed for immunohistochemical staining. Atorvastatin administration after brain injury significantly promoted the restoration of spatial memory but did not reduce sensorimotor functional deficits. Treatment of TBI with atorvastatin increased neuronal survival in the CA3 region and the lesion boundary zone and prevented the loss of neuronal processes of damaged neurons in the hippocampal CA3 region but not in the lesion boundary zone on Day 15 after TBI. The protective effect of atorvastatin on the injured neurons perhaps is mediated by increasing the density of vessels in the lesion boundary zone and the hippocampus after TBI.

Conclusions: . These data indicate that atorvastatin is beneficial in the treatment of TBI in female rats, although the effect may differ between sexes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / pharmacology*
  • Atorvastatin
  • Brain Injuries / drug therapy*
  • Brain Injuries / pathology
  • Brain Injuries / veterinary
  • Cell Survival
  • Female
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / pharmacology*
  • Immunohistochemistry
  • Memory / drug effects*
  • Neovascularization, Physiologic
  • Neurons / physiology
  • Pyrroles / administration & dosage
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Wistar
  • Reproducibility of Results
  • Sex Factors

Substances

  • Anticholesteremic Agents
  • Heptanoic Acids
  • Pyrroles
  • Atorvastatin