Neuroprotective effect of atorvastatin involves suppression of TNF-α and upregulation of IL-10 in a rat model of intracerebral hemorrhage

Cell Biochem Biophys. 2013 Jun;66(2):337-46. doi: 10.1007/s12013-012-9453-z.

Abstract

We evaluated the neuroprotective effects of atorvastatin (2, 5, and 10 mg/kg) on experimentally induced intracerebral hemorrhage (ICH) in adult rats; controls were administered PBS. Plasma TNF-α and IL-10 levels before and after ICH were analyzed at various time points by enzyme-linked immunosorbent assay (ELISA) and neurological behavior of rats was assessed by climbing scores. At 3-days postoperatively, brain water contents and TNF-α/IL-10 expression in brain tissue were determined. Histopathological changes and microglial cells in the brain tissue were evaluated by light-microscopy. Post-ICH neurological deficits differed significantly between sham-operated group A and experimental-ICH group B (P < 0.05). Brain water contents were significantly less in group A than in group B (P < 0.05). Significant differences (P < 0.05) between two groups were observed regarding activated microglia, TNF-α and IL-10 levels. Compared with group B, neurological deficits, brain water contents, pathological changes, and activated microglia were reduced (P < 0.05) in groups C (Experimental-ICH + atorvastatin 2 mg/kg), D (Experimental-ICH + atorvastatin 5 mg/kg) and E (Experimental-ICH + atorvastatin 10 mg/kg). Atorvastatin-induced a dose-dependent reduction of TNF-α and increase of IL-10 levels (P < 0.05). Therefore, it was concluded that atorvastatin improved neurofunctional rehabilitation in rats through the suppression of cytokines-mediated inflammatory response and attenuation of brain damage following intracerebral hemorrhage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atorvastatin
  • Behavior, Animal / drug effects
  • Brain Edema / metabolism
  • Brain Edema / pathology
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / metabolism
  • Cerebral Hemorrhage / pathology
  • Disease Models, Animal
  • Heptanoic Acids / pharmacology
  • Heptanoic Acids / therapeutic use*
  • Interleukin-10 / metabolism*
  • Male
  • Microglia / pathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism*
  • Up-Regulation / drug effects

Substances

  • Heptanoic Acids
  • Neuroprotective Agents
  • Pyrroles
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Atorvastatin