The interleukin-8 (IL-8/CXCL8) receptor inhibitor reparixin improves neurological deficits and reduces long-term inflammation in permanent and transient cerebral ischemia in rats

Mol Med. 2007 Mar-Apr;13(3-4):125-33. doi: 10.2119/2007–00008.Villa.

Abstract

Leukocyte infiltration is viewed as a pharmacological target in cerebral ischemia. We previously reported that reparixin, a CXCL8 receptor blocker that inhibits neutrophil infiltration, and related molecules can reduce infarct size in a rat model of transient middle cerebral artery occlusion (MCAO). The study aims were to compare the effects of reparixin in transient and permanent MCAO using varied treatment schedules and therapeutic windows to evaluate effects on long-term neurological deficits and late inflammatory response. Reparixin, administered for 1 to 3 days, 3.5 to 6 h after MCAO, ameliorates neurological function recovery and inhibits long-term inflammation. The infarct size reduction at 24 h, evaluated by TTC staining, is more pronounced in transient MCAO. MRI analysis identified a decrease in the progression of infarct size by reparixin that was more evident at 48 h in permanent MCAO, and was associated with a significantly improved recovery from long-term neurological deficits.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / immunology
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Drug Administration Schedule
  • Immunohistochemistry
  • Infarction, Middle Cerebral Artery / etiology
  • Infarction, Middle Cerebral Artery / surgery
  • Inflammation / drug therapy*
  • Ischemic Attack, Transient / drug therapy*
  • Ischemic Attack, Transient / etiology
  • Ischemic Attack, Transient / pathology
  • Male
  • Neuroprotective Agents / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Interleukin-8 / antagonists & inhibitors*
  • Sulfonamides / pharmacology*

Substances

  • Neuroprotective Agents
  • Receptors, Interleukin-8
  • Sulfonamides
  • reparixin