myelin-basic-protein and Meningitis--Pneumococcal

At present, the great attention is given to the neurospecific markers as their elevated level in the cerebrospinal fluid corresponds to the degree of destruction of relevant CNS cells. Therefore, actual direction of the studies of the pathogenesis and diagnosis of CNS diseases is to determine levels of neurospecific markers in the cerebrospinal fluid (CSF). The purpose of the study was to evaluate the diagnostic and prognostic role of NSE, S-100 protein, GFAP and MBP levels in CSF of patients with acute bacterial meningitis. S-100 protein, NSE, GFAP and MBP levels in CSF of patients with acute pneumococcal and meningococcal meningitis were determined during admission and after 10-12 days of treatment. Patients were divided into groups depending on the etiology and severity of the disease. 60 cases of acute bacterial meningitis, as a study group, and 12 cases with acute respiratory infection and meningism, as a control group, were analyzed. It is shown that CSF levels of NSE, S-100 protein, GFAP and MBP on the first day of admission were significantly increased (P<0,05), depending on the severity of the disease. The highest levels of neurospecific markers have been identified in non-survivors (P<0,001). The concentration changes of CSF neurospecific markers are found to be helpful as a diagnostic and prognostic marker in acute bacterial meningitis.

Topics: Acute Disease; Adolescent; Adult; Aged; Biomarkers; Glial Fibrillary Acidic Protein; Humans; Meningitis, Bacterial; Meningitis, Meningococcal; Meningitis, Pneumococcal; Middle Aged; Myelin Basic Protein; Phosphopyruvate Hydratase; S100 Proteins; Severity of Illness Index; Young Adult

Pneumococcal meningitis causes neurological sequelae, including learning and memory deficits in up to half of the survivors. In both humans and in animal models of the disease, there is apoptotic cell death in the hippocampus, a brain region involved in learning and memory function. We previously demonstrated that in an infant rat model of pneumococcal meningitis, there is activation of the kynurenine (KYN) pathway in the hippocampus, and that there was a positive correlation between the concentration of 3-hydroxykynurenine and the extent of hippocampal apoptosis. To clarify the role of the KYN pathway in the pathogenesis of hippocampal apoptosis in pneumococcal meningitis, we specifically inhibited 2 key enzymes of the KYN pathway and assessed hippocampal apoptosis, KYN pathway metabolites, and nicotinamide adenine dinucleotide (NAD) concentrations by high-performance liquid chromatography. Pharmacological inhibition of kynurenine 3-hydroxylase and kynureninase led to decreased cellular NAD levels and increased apoptosis in the hippocampus. The cerebrospinal fluid levels of tumor necrosis factor and interleukin-1α and -β were not affected. Our data suggest that activation of the KYN pathway in pneumococcal meningitis is neuroprotective by compensating for an increased NAD demand caused by infection and inflammation;this mechanism may prevent energy failure and apoptosis in the hippocampus.

Topics: Animals; Animals, Newborn; Apoptosis; Chromatography, High Pressure Liquid; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Energy Metabolism; Hippocampus; Kynurenine; Meningitis, Pneumococcal; Myelin Basic Protein; NAD; Rats; Rats, Wistar; Signal Transduction; Sulfonamides; Thiazoles