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Role of peroxynitrite as a mediator of pathophysiological alterations in experimental pneumococcal meningitis

S Kastenbauer1, U Koedel, H W Pfister

  • 1Department of Neurology, Grosshadern Clinic, Ludwig-Maximilians-University, 81377 Munich, Germany.

The Journal of Infectious Diseases
|September 9, 1999
PubMed

Insights

Peroxynitrite contributes to brain damage in pneumococcal meningitis. Uric acid, a peroxynitrite scavenger, reduced intracranial pressure, inflammation, and blood-brain barrier leakage in rats.

Area of Science:

  • Neuroscience
  • Pathology
  • Biochemistry

Background:

  • Bacterial meningitis is a severe central nervous system infection.
  • Peroxynitrite is a reactive nitrogen species implicated in inflammatory processes.

Purpose of the Study:

  • To investigate the role of peroxynitrite in a rat model of pneumococcal meningitis.
  • To evaluate the therapeutic potential of uric acid as a peroxynitrite scavenger.

Main Methods:

  • Immunohistochemistry to detect nitrotyrosine (peroxynitrite marker).
  • Evans blue staining to assess blood-brain barrier permeability.
  • Measurement of intracranial pressure and cerebrospinal fluid white blood cell count.

Main Results:

  • Nitrotyrosine deposition was observed in the subarachnoid space, colocalizing with blood-brain barrier disruption.
  • Uric acid treatment significantly reduced intracranial pressure (P<.05).
  • Uric acid significantly decreased cerebrospinal fluid white blood cell count and blood-brain barrier leakage (P<.05).

Conclusions:

  • Peroxynitrite plays a critical role in the pathophysiology of pneumococcal meningitis.
  • Scavenging peroxynitrite with uric acid demonstrates therapeutic potential in reducing meningitis-induced damage.

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