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Dexamethasone regulation of matrix metalloproteinase expression in experimental pneumococcal meningitis

Xinjie Liu1, Qizheng Han, Ruopeng Sun

  • 1Department of Pediatrics, Qilu Hospital, Shandong University, No. 107 Wen Hua Xi Road, Jinan 250012, China. liuxinjie2005@sina.com

Brain Research
|April 1, 2008
PubMed

Insights

Matrix metalloproteinases (MMPs) are implicated in bacterial meningitis. This study found dexamethasone, when used with antibiotics, down-regulated MMP-9 expression, suggesting a beneficial therapeutic effect in pneumococcal meningitis.

Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Pharmacology

Background:

  • Matrix metalloproteinases (MMPs) play a role in bacterial meningitis pathophysiology, facilitating leukocyte extravasation and brain edema.
  • Dexamethasone shows promise as an adjunctive therapy in meningitis, but its specific role in pneumococcal meningitis and its effect on MMPs remain unclear.
  • The impact of antibiotics on MMPs during bacterial meningitis has not been previously evaluated.

Purpose of the Study:

  • To investigate the induction and expression of MMPs, specifically MMP-9 and MMP-2, in experimental pneumococcal meningitis.
  • To examine the regulatory effects of dexamethasone and antibiotics on MMPs during the treatment of pneumococcal meningitis.

Main Methods:

  • Experimental pneumococcal meningitis was induced in rats.
  • Expression of MMP-9 and MMP-2 mRNA in brain tissue and their activity in cerebrospinal fluid (CSF) were measured.
  • Rats were treated with antibiotics alone or in combination with dexamethasone.

Main Results:

  • MMP-9 mRNA expression was significantly upregulated in the brains of rats with pneumococcal meningitis.
  • Antibiotic treatment alone led to a dose-dependent upregulation of MMP-9 expression.
  • Combined treatment with antibiotics and dexamethasone significantly downregulated MMP-9 expression and activity, unlike antibiotic treatment alone.

Conclusions:

  • Antibiotic therapy may increase MMP-9 expression in pneumococcal meningitis.
  • Dexamethasone, as an adjunctive therapy with antibiotics, appears to inhibit MMP-9 expression and activity.
  • Dexamethasone may exert beneficial effects in bacterial meningitis by downregulating MMP-9.

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