Decreased focal inflammatory response by G-CSF may improve stroke outcome after transient middle cerebral artery occlusion in rats

J Neurosci Res. 2007 Aug 1;85(10):2167-74. doi: 10.1002/jnr.21341.

Abstract

Recent studies have shown that administration of granulocyte colony-stimulating factor (G-CSF) is neuroprotective. However, the precise mechanisms of the neuroprotective effect of G-CSF are not entirely known. We carried out 90-min transient middle cerebral occlusion (tMCAO) of rats. The rats were injected with vehicle or G-CSF (50 mug/kg) immediately after reperfusion and sacrificed 8, 24, or 72 hr later. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was carried out using brain sections of 72 hr, and immunohistochemistry was carried out with those of 8, 24, and 72 hr. TTC-staining showed a significant reduction of infarct volume in the G-CSF-treated group (**P < 0.01). Immunohistochemistry showed a significant decrease of the number of cells expressing tumor necrosis factor-alpha (TNF-alpha) at 8-72 hr, transforming growth factor-beta (TGF-beta) and inducible nitric oxide synthase (iNOS) at 24 and 72 hr after tMCAO in the peri-ischemic area (*P < 0.05 each). Our data suggest that the suppression of inflammatory cytokines and iNOS expression may be one mechanism of neuroprotection by G-CSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Brain / metabolism
  • Brain Ischemia / etiology
  • Brain Ischemia / metabolism
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Immunohistochemistry
  • Infarction, Middle Cerebral Artery / complications*
  • Inflammation / etiology
  • Inflammation / pathology*
  • Male
  • Nervous System / physiopathology
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide Synthase Type II / metabolism
  • Rats
  • Rats, Wistar
  • Stroke / etiology
  • Stroke / pathology
  • Stroke / physiopathology*
  • Time Factors
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Neuroprotective Agents
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Granulocyte Colony-Stimulating Factor
  • Nitric Oxide Synthase Type II