Activated astrocytes, but not pyramidal cells, increase glucose utilization in rat hippocampal CA1 subfield after ischemia.
The local cerebral glucose utilization (CMRglc) in the damaged rat hippocampal CA1 subfield increases 7 days after 10 min of cerebral ischemia. We have used the N-methyl-D-aspartate antagonist (NMDA antagonist) ketamine in rats 7 days after sham operation or cerebral ischemia to determine whether the elevated postischemic CMRglc of the CA1 subfield is due to long-lasting hyperexcitation of surviving or injured neurons, or, alternatively, to the metabolism of other cell types. The autoradiographic data were interpreted with the aid of histochemical analysis of the postischemic hippocampal cell changes. Anesthetic doses of ketamine significantly reduced the CMRglc in the CA1 strata oriens, pyramidale and radiatum of sham-operated rats, while the postischemic increases in CMRglc in these hippocampal CA1 strata were not affected by ketamine. In addition, there were ketamine-induced increases in the CMRglc of the CA1 stratum lacunosum moleculare of both sham-operated and postischemic rats. The immunoreactivity of the microtubule-associated protein 2 (MAP2), a postsynaptic protein marker, was decreased markedly in the CA1 subfield in postischemic rats, while the presynaptic protein marker, synaptophysin, remained the same in sham-operated and postischemic rats. The glial fibrillary acidic protein (GFAP) immunoreactivity of astrocytes raised markedly in the ischemically damaged CA1 subfield. Although it could be demonstrated that presynaptic terminals remain intact in the postischemic damaged CA1 subfield, the lacking ketamine effect on CA1 pyramidal neurons indicated that the increase in CMRglc in this brain area is not due to postsynaptic neural hyperexcitation, but probably has to be attributed to astrocytes activated by neuronal damage.
Rischke
R
R
Institut für Pharmakologie und Toxikologie, Philipps-Universität, Ketzerbach, Marburg, BRD.
Rami
A
A
Bachmann
U
U
Rabié
A
A
Krieglstein
J
J
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001345:Autoradiography; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D007649:Ketamine / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007649:Ketamine; D005947:Glucose