Therapeutic potential of peroxisome proliferator-activated receptor γ agonist rosiglitazone in cerebral vasospasm after a rat experimental subarachnoid hemorrhage model

J Neurol Sci. 2011 Jun 15;305(1-2):85-91. doi: 10.1016/j.jns.2011.03.006. Epub 2011 Mar 26.

Abstract

The pathogenesis of cerebral vasospasm is closely associated with inflammation and immune response in arterial walls. Recently, the authors proved the key role of Toll-like receptor (TLR)4 in the development of vasospasm in experimental subarachnoid hemorrhage (SAH) model. Because peroxisome proliferator-activated receptor (PPAR) gamma agonists are identified as effective inhibitors of TLR4 activation, we investigated the anti-inflammation properties of PPAR-gamma agonist rosiglitazone in basilar arteries in a rat experimental SAH model and evaluated the effects of rosiglitazone on vasospasm. Inflammatory responses in basilar arteries were assessed by immunohistochemical staining for intercellular molecule (ICAM)-1 and myeloperoxidase (MPO). Expression of TLR4 was determined by western blot analysis. The degree of cerebral vasospasm was evaluated by measuring the mean diameter and cross-sectional area of basilar arteries. Rosiglitazone suppressed the SAH-induced inflammatory responses in basilar arteries by inhibiting the TLR4 signalling. Furthermore, rosiglitazone could attenuate cerebral vasospasm following SAH. Therefore, we suggested that PPAR-gamma agonists may be potential therapeutic agents for cerebral vasospasm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Male
  • PPAR gamma / agonists*
  • PPAR gamma / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Rosiglitazone
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / metabolism*
  • Subarachnoid Hemorrhage / pathology
  • Thiazolidinediones / therapeutic use*
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / metabolism
  • Toll-Like Receptor 4 / physiology
  • Vasodilator Agents / therapeutic use*
  • Vasospasm, Intracranial / drug therapy*
  • Vasospasm, Intracranial / etiology
  • Vasospasm, Intracranial / metabolism*

Substances

  • PPAR gamma
  • Thiazolidinediones
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Vasodilator Agents
  • Rosiglitazone