Simvastatin attenuates microglial cells and astrocyte activation and decreases interleukin-1beta level after traumatic brain injury.

Abstract:

OBJECTIVE:Our previous studies demonstrated that simvastatin promotes neurological functional recovery after traumatic brain injury (TBI) in rat; however, the underlying mechanisms remain poorly understood. The purpose of this study was to investigate the anti-inflammatory effect of simvastatin by measuring the level of cytokines and activation of glial cells. METHODS:Controlled cortical impact injury was performed in adult male Wistar rats. The rats were randomly divided into 3 groups: sham, saline control group, and simvastatin treatment group. Simvastatin was administered orally starting at day 1 after TBI until animals were killed at days 1, 3, 7, 14, and 35 after treatment. Functional outcome was measured using modified neurological severity scores. Enzyme-linked immunosorbent assay and immunohistochemical staining were used to measure the expression of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha and to identify activated microglial cells and astrocytes. RESULTS:At days 1 and 3 after simvastatin or saline treatment, cytokine levels in the lesion boundary zone were significantly higher in the simvastatin- and saline-treated rats compared with the sham group, peaking at day 3. Simvastatin only reduced the level of IL-1beta but not IL-6 and tumor necrosis factor-alpha, compared with the saline group. Also, simvastatin significantly reduced the number of activated microglial cells and astrocytes compared with the saline control animals. There was also a trend toward improvement of modified neurological severity score, reaching statistical significance (P = 0.003) toward the end of the trial. CONCLUSION:Our data demonstrate that TBI causes inflammatory reaction, including increased levels of IL-1beta, IL-6, and tumor necrosis factor-alpha, as well as activated microglial cells. Simvastatin selectively reduces IL-1beta expression and inhibits the activation of microglial cells and astrocytes after TBI, which might be one of the mechanisms underlying the therapeutic benefits of simvastatin treatment of TBI.

journal_name

Neurosurgery

journal_title

Neurosurgery

authors

Li B,Mahmood A,Lu D,Wu H,Xiong Y,Qu C,Chopp M

doi

10.1227/01.NEU.0000346272.76537.DC

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

179-85; discussion 185-6

issue

1

eissn

0148-396X

issn

1524-4040

pii

00006123-200907000-00031

journal_volume

65

pub_type

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