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Antioxidants attenuate microvascular changes in the early phase of experimental pneumococcal meningitis in rats
H W Pfister1, U Koedel, S Lorenzl
1Department of Neurology, University of Munich, FRG.
Background And Purpose:
We tested in a rat meningitis model 1) whether pneumococcal cell wall components are capable of producing changes in regional cerebral blood flow, brain water content, and intracranial pressure similar to those we have already observed after intracisternal inoculation of live pneumococci and 2) whether antioxidants would modulate these alterations in the early phase of meningitis.
Methods:
Regional cerebral blood flow as measured by laser Doppler flowmetry and intracranial pressure were monitored continuously for 4 hours after intracisternal challenge. Brain edema formation was assessed by brain water content determinations. We investigated the following groups: rats challenged intracisternally with the whole intact pneumococcal cell wall (n = 7) or the pneumococcal cell wall hydrolyzed by the M1-muramidase (n = 7); rats injected intracisternally with phosphate-buffered saline (n = 6); rats pretreated intravenously with superoxide dismutase conjugated with polyethylene glycol (10,000 units/kg) and injected intracisternally with cell wall components (n = 5) or phosphate-buffered saline (n = 6); rats injected intracisternally with phosphate-buffered saline and pretreated intravenously with polyethylene glycol (10% solution, 1.2 ml/kg, n = 5) or continuously treated with intravenous free superoxide dismutase (22,000 units/kg per hour, n = 6); and rats continuously treated intravenously with deferoxamine mesylate (10 mg/kg per hour) and injected intracisternally with cell wall components (n = 6) or phosphate-buffered saline (n = 7).
Results:
Both pneumococcal cell wall preparations produced a significant increase in regional cerebral blood flow, intracranial pressure, and brain water content. Conjugated superoxide dismutase as well as deferoxamine prevented the increase in intracranial pressure and brain water content. In addition, the increase in regional cerebral blood flow as observed in untreated, cell wall-challenged rats (baseline, 100%; 183.1 +/- 12.3% after 4 hours, mean +/- SEM) was significantly attenuated by administration of both conjugated superoxide dismutase (136.6 +/- 14.1%) and deferoxamine (149.8 +/- 8.2%) (p < 0.05). Polyethylene glycol-conjugated superoxide dismutase alone produced an increase in regional cerebral blood flow (125.6 +/- 8.7% after 4 hours). We found that polyethylene glycol per se accounts for this action.
Conclusions:
These data show that pneumococcal cell wall components containing teichoic acid produce changes in regional cerebral blood flow, intracranial pressure, and brain water content and that oxygen radicals contribute to these pathophysiological alterations in the early phase of experimental pneumococcal meningitis.
Insights
Pneumococcal cell wall components trigger harmful changes in brain blood flow, pressure, and water content during meningitis. Antioxidants like superoxide dismutase and deferoxamine help mitigate these early-stage effects.
Area of Science:
- Neuroscience
- Pathophysiology
- Pharmacology
Background:
- Pneumococcal meningitis involves complex pathophysiological changes.
- Cell wall components of Streptococcus pneumoniae are implicated in meningitis progression.
Purpose of the Study:
- To investigate if pneumococcal cell wall components alter cerebral blood flow, brain water content, and intracranial pressure.
- To determine if antioxidants can modulate these early-phase meningitis alterations.
Main Methods:
- Rats were challenged intracisternally with pneumococcal cell wall components or controls.
- Regional cerebral blood flow, intracranial pressure, and brain water content were measured.
- Antioxidants (superoxide dismutase, deferoxamine) were administered to assess their modulatory effects.
Main Results:
- Pneumococcal cell wall components significantly increased cerebral blood flow, intracranial pressure, and brain water content.
- Superoxide dismutase and deferoxamine administration attenuated these increases.
- Polyethylene glycol-conjugated superoxide dismutase alone showed a minor increase in cerebral blood flow, attributed to the carrier.
Conclusions:
- Pneumococcal cell wall components, including teichoic acid, induce significant pathophysiological changes in experimental meningitis.
- Oxygen radicals play a crucial role in these early-stage alterations.
- Antioxidant therapies show potential in managing early-phase pneumococcal meningitis.