Abstract

BackgroundBacterial meningitis is often associated with cerebral compromise which may be responsible for neurological sequelae in nearly half of the survivors. Little is known about the mechanisms of CNS involvement in bacterial meningitis. Several studies have provided substantial evidence for the key role of nitric oxide (NO) and reactive oxygen species in the complex pathophysiology of bacterial meningitis.MethodsIn the present study, serum and CSF levels of NO, lipid peroxide (LPO) (mediators for oxidative stress and lipid peroxidation); total thiol, superoxide dismutase (SOD) (antioxidant mediators) and S-100B protein (mediator of astrocytes activation and injury), were investigated in children with bacterial meningitis (n = 40). Albumin ratio (CSF/serum) is a marker of blood-CSF barriers integrity, while mediator index (mediator ratio/albumin ratio) is indicative of intrathecal synthesis.ResultsCompared to normal children (n = 20), patients had lower serum albumin but higher NO, LPO, total thiol, SOD and S-100B. The ratios and indices of NO and LPO indicate blood-CSF barriers dysfunction, while the ratio of S-100B indicates intrathecal synthesis. Changes were marked among patients with positive culture and those with neurological complications. Positive correlation was found between NO index with CSF WBCs (r = 0.319, p < 0.05); CSF-LPO with CSF-protein (r = 0.423, p < 0.01); total thiol with LPO indices (r = 0.725, p < 0.0001); S-100B and Pediatric Glasow Coma Scores (0.608, p < 0.0001); CSF-LPO with CSF-S-100B (r = 0.482, p < 0.002); serum-total thiol with serum S-100B (r = 0.423, p < 0.01).ConclusionThis study suggests that loss of integrity of brain-CSF barriers, oxidative stress and S-100B may contribute to the severity and neurological complications of bacterial meningitis.

Highlights

  • Bacterial meningitis is often associated with cerebral compromise which may be responsible for neurological sequelae in nearly half of the survivors

  • cerebrospinal fluid (CSF) biochemistries of the samples examined confirmed the diagnosis of bacterial meningitis as compared to our normal lab reference values

  • The results of this study may suggest the following: 1) Dysfunction of blood-CSF barriers occurs with bacterial meningitis, 2) Oxidative stress has an important role in the pathogenesis of bacterial meningitis, 2) Brain damage does occur in bacterial meningitis as evidence by increased intrathecal synthesis of S-100B, nitric oxide (NO) and lipid peroxide (LPO) biomarkers, 3) the finding of association between the levels of mediators of oxidative stress, antioxidants and S100B may suggest their role in disease severity and the occurrence of neurological complications

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Summary

Introduction

Bacterial meningitis is often associated with cerebral compromise which may be responsible for neurological sequelae in nearly half of the survivors. Bacterial meningitis is the most severe and frequent infection of the central nervous system (CNS). It remains an important public health problem worldwide[1]. Grimwood et al [4] evaluated 109 children at adolescence (12 years of age) who had survived bacterial meningitis at 7 years of age and found that many of the deficits identified at the 7-year follow-up had persisted, with 9% of the patients had major neurological, auditory, or intellectual impairments and 30% had less severe disabilities, compared with 11% of the controls

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