Brain glutamine synthetase increases following cerebral ischemia in the rat.
Changes in astrocyte glutamine synthetase (GS) in postischemic rat brain were evaluated and correlated with regional neuronal vulnerability or resistance to ischemia. Rats subjected to 20 or 30 min of cerebral ischemia were allowed to survive for 3 or 24 h after ischemia; normal animals served as controls. Resultant neuronal necrosis was severe in the striatum by 24 h and in the CA1 region of the hippocampus at 72 h; neurons in paramedian cortex and CA3 region of the hippocampus were not permanently damaged. Glutamine synthetase (GS) immunocytochemistry was performed on vibratome sections of paraformaldehyde-fixed brains and enzyme activity was assayed in frozen samples of cerebral cortex, striatum and hippocampus. At 3 and 24 h after ischemia, GS immunoreactivity increased and was secondary to enlargement of GS-positive cell bodies and processes as well as to increased numbers of GS-positive astrocytes. Enzyme activity also increased in cortex, striatum and hippocampus at 3 and 24 h (P less than or equal to 0.03). This study shows that increase in astrocyte GS occurs rapidly after ischemia, and prior studies indicate that this increase occurs in parallel with proliferative changes in astrocyte organelles. The results also suggest that astrocyte metabolism of glutamate increases after ischemia. The increased capacity for glutamine synthetase may be important in normalizing extracellular glutamate following ischemia and protecting brain from the neurotoxic effects of this excitatory amino acid.
Department of Pathology (Neuropathology), Cornell University Medical College, New York, NY 10021.
C K
CK
Petito
M C
MC
Chung
L M
LM
Verkhovsky
A J
AJ
Cooper
D000818:Animals; D001253:Astrocytes / Q000201:enzymology* / Q000648:ultrastructure; D001921:Brain / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D005974:Glutamate-Ammonia Ligase