Cerebellar glutamine synthetase in children after hypoxia or ischemia

Glutamate has been implicated in the pathophysiology of acute hypoxic-ischemic encephalopathy. Glutamine synthetase is an enzyme found in astrocytes that converts glutamate to its nontoxic analogue, glutamine. The present study tests the hypothesis that brain glutamine synthetase activity increases in response to acute hypoxic-ischemic insults and not in response to chronic hypoxia-ischemia or non-hypoxic-ischemic neurological disease.

Frozen sections of cerebellum from children who died with acute or chronic hypoxic-ischemic insults or chronic non-hypoxic-ischemic neurological disease were spectrophotometrically assayed for glutamine synthetase activity by an observer who was blinded to the clinical group assignment of each specimen. Enzyme activity was elevated in specimens from children with acute hypoxic-ischemic insults (mean 6.5; range 5.4-7.2 units/g wet tissue wt) as compared with those from patients with chronic hypoxia-ischemia (mean 2.8; range 0.7-10.2 units/g wet tissue wt) or with non-hypoxic-ischemic neurological disease (mean 2.6; range 1.3-3.9 units/g wet tissue wt). This difference was not due to differences in the degree of histological astrocytosis or edema among the specimens. Statistical analysis by the Kruskal-Wallis one-way analysis of variance by ranks test indicates that the three data groups do not come from one population (p less than 0.05).

These results support the notion that glutamine synthetase activity increases in response to acute hypoxic-ischemic nervous system injury in children and that other compensatory mechanisms prevail in the case of chronic hypoxic-ischemic insults.