Progesterone attenuates early brain injury after subarachnoid hemorrhage in rats

Neurosci Lett. 2013 May 24:543:163-7. doi: 10.1016/j.neulet.2013.03.005. Epub 2013 Mar 13.

Abstract

Background and purpose: Although the neuroprotective effects of progesterone against early brain injury (EBI) after trauma have been demonstrated in several studies, whether progesterone reduces EBI after subarachnoid hemorrhage (SAH) remains unknown. In this study, we explored the effect of progesterone on cell apoptosis, stability of the blood-brain barrier (BBB), brain edema, and mortality in male Sprague-Dawley rats subjected to subarachnoid hemorrhage-induced EBI by endovascular perforation.

Method: Rats (n=66) were randomly assigned to sham, SAH+vehicle, and SAH+progesterone groups. Progesterone (16 mg/kg) or an equal volume of vehicle was administered at 1h, 6h and 12h after SAH. Mortality within 24h, neurological scores, brain edema, Evans blue dye extravasation, cell apoptosis, and the expression of caspase-3 and matrix metalloproteinase (MMP)-9 were assayed after 24h of SAH.

Result: Progesterone treatment significantly reduced mortality, brain edema, Evans blue dye extravasation, cell apoptosis, expression of caspase-3 and MMP-9, and improved neurological scores compared with the vehicle group.

Conclusion: Progesterone may reduce EBI after SAH by inhibiting cell apoptosis and stabilizing the BBB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Brain Edema / drug therapy
  • Brain Edema / pathology
  • Brain Injuries / drug therapy*
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology
  • Caspase 3 / metabolism
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Permeability
  • Progesterone / pharmacology*
  • Progesterone / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / pathology
  • Subarachnoid Hemorrhage / physiopathology

Substances

  • Neuroprotective Agents
  • Progesterone
  • Caspase 3
  • Matrix Metalloproteinase 9