Lovastatin improves histological and functional outcomes and reduces inflammation after experimental traumatic brain injury

Szu Fu Chen, Tai Ho Hung, Chien Cheng Chen, Kuei Han Lin, Ya Ni Huang, Hung Chih Tsai, Jia Yi Wang

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) triggers a complex sequence of inflammatory responses that contribute to secondary injury. Statins have demonstrated neuroprotective effects against brain injury, but the underlying mechanisms remain unclear. This study evaluated the effects of lovastatin on a rat model of controlled cortical impact (CCI) injury. Our two hypotheses were that pre-administration of lovastatin would reduce functional deficits and extent of anatomical brain damage and that lovastatin would attenuate levels of pro-inflammatory cytokines. Rats were injected with lovastatin (4 mg/kg) or vehicle for 5 days and subjected to CCI. Neurological status was evaluated using rotarod and adhesive removal tests. Contusion volume and neuronal degeneration were examined using cresyl violet and FluoroJade B (FJB) histochemistry. Levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA and protein were assessed by real-time quantitative reverse transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. Lovastatin significantly improved performance on both the rotarod and adhesive removal tests before post-injury day 7. Lovastatin also significantly reduced contusion volume (20%) and number of FJB-positive degenerating neurons (35%) at 4 days. These changes were associated with a significant decrease in levels of TNF-α and IL-1β mRNA and protein at the contusion site at 6 h and 4 days, respectively. Our results show that pre-administration of lovastatin improved functional outcomes and reduced extent of brain damage, with a concomitant decrease in tissue levels of TNF-α and IL-1β mRNA and protein. These findings suggest that lovastatin's protective mechanisms may be partly attributed to a dampening of the inflammatory response.

Original languageEnglish
Pages (from-to)288-298
Number of pages11
JournalLife Sciences
Volume81
Issue number4
DOIs
Publication statusPublished - Jul 4 2007
Externally publishedYes

Keywords

  • Cytokines
  • Inflammation
  • Lovastatin
  • Traumatic brain injury

ASJC Scopus subject areas

  • Pharmacology

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