This study was done to elucidate the mechanism of hypoglycorrhachia and elevated lactate concentrations leading to neuronal dysfunction in neonatal meningitis, and to determine the effects of induced hyperglycemia on these disturbances. Thirty-eight newborn piglets were divided into three groups: 12 in the control group (CG), 12 in the normoglycemic meningitis group (NG), and 14 in the hyperglycemic meningitis group (HG). Meningitis was induced by intracisternal injection of 108 cfu of Escherichia coli. Hyperglycemia (blood glucose 300-400 mg dl-1) was induced and maintained for 60 min before induction of meningitis and throughout the experiment using modified glucose clamp technique. CSF-to-blood glucose ratio decreased significantly in NG. In HG, baseline CSF-to-blood glucose ratio was lower than two other groups, but increased at 1 h after induction of meningitis. CSF lactate concentration was increased progressively in both meningitis groups, and positively correlated with CSF leukocyte numbers (r=0.41, p<0.001) and TNF-alpha level (r=0.43, p<0.001). Brain glucose concentration was significantly increased in HG and showed inverse correlation with CSF leukocyte numbers (r=-0.59, p<0.01). Brain lactate concentration was not significantly different among three groups and positively correlated with the CSF TNF-alpha level (r=0.51, p<0.05). Lipid peroxidation products were increased in NG. Na+,K+-ATPase activity, ATP/PCr concentrations were not different among three groups. Increased intracranial pressure, CSF pleocytosis (214+/-59 vs. 437+/-214/mm3, p<0.02) and increased lipid peroxidation products observed in NG were reduced in HG. These results suggest that hypoglycorrhachia and elevated lactate concentration in the CSF during meningitis originates primarily from the increased anaerobic glycolysis in the subarachnoid space, induced by TNF-alpha and leukocytes. Induced hyperglycemia attenuates the inflammatory responses of meningitis and might be beneficial by providing an increased glucose delivery to meet its increased demand in meningitis.
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