Effects of atorvastatin on the inflammation regulation and elimination of subdural hematoma in rats

J Neurol Sci. 2014 Jun 15;341(1-2):88-96. doi: 10.1016/j.jns.2014.04.009. Epub 2014 Apr 13.

Abstract

Background and purpose: It is well known that inflammation influence chronic subdural hematoma (CSDH) formation to a large extent. Atorvastatin has pleiotropic effects on restraining inflammation and promoting angiogenesis besides its cholesterol-lowering function. Hence, atorvastatin may induce anti-inflammation effects and facilitate therapeutic effects for subdural hematoma (SDH).

Methods: Adult male Wistar rats were subjected to SDH and successful establishment of SDH was confirmed by magnetic resonance imaging (MRI). The treatment was initiated 6 hours after SDH induction. For the treatment, rats suffering SDH were randomly divided into saline group (the control group, rats were treated by saline, n=29) and atorvastatin group (rats were treated by atorvastatin, 3mg/kg/day, n=30). The volume of lesion before treatment as well as on day 2 and day 7 after initial treatment was measured by MRI, respectively. The behaviors before SDH induction and on the days 1, 3, 5 and 7 after the initial treatment were dynamically evaluated. Gene expression, cytokine secretion and the number of neutrophilic granulocyte and vascular density were measured in both neomembrane and SDH lesion on the day 2 and day 7 after the initial treatment.

Results: It was found that the SDH rats treated by atorvastatin had a better behavior recovery compared to the ones treated by saline (p<0.05). By virtue of MRI scanning, it was revealed that SDH volumes were eliminated at a high speed by administration of atorvastatin than that of saline. With the help of the microscopic examination in the neomembrane, it was detected that the density of CD31+ neovasculars in the atorvastatin group was significantly higher than that in the saline group and the number of neutrophilic granulocyte in the atorvastatin group is less than that in the saline group. In comparison with saline treatment, the atorvastatin treatment did not change IL-10 expression and secretion, but it significantly decreased TNF-α and IL-6 level as well as VEGF gene expression.

Conclusions: Atorvastatin treatment may eliminate SDH and improve the neural function of the rats through its anti-inflammatory effects. Hence, it indicated that statin induced inflammatory modulation might play a significant role in rats' SDH elimination and the functional recovery.

Keywords: Angiogenesis; Atorvastatin; Cytokine; ELISA; Inflammation; Subdural hematoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Atorvastatin
  • Blood Cell Count
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Hematoma, Subdural / complications*
  • Hematoma, Subdural / drug therapy*
  • Heptanoic Acids / therapeutic use*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Image Processing, Computer-Assisted
  • Inflammation / drug therapy*
  • Inflammation / etiology*
  • Lipids / analysis
  • Magnetic Resonance Imaging
  • Male
  • Neurologic Examination
  • Pyrroles / therapeutic use*
  • Rats
  • Rats, Wistar
  • Time Factors

Substances

  • Cytokines
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Pyrroles
  • Atorvastatin