MK801 decreases glutamate release and oxidative metabolism during hypoglycemic coma in piglets.
Publication/Presentation Date
6-29-2001
Abstract
Hypoglycemic coma increases extracellular excitatory amino acids, which mediate hypoglycemic neuronal degeneration. Cerebral oxygen consumption increases during hypoglycemic coma in piglets. We tested the hypothesis that the NMDA-receptor antagonist dizocilpine (MK801) attenuates the increase in cerebral oxygen consumption during hypoglycemia. We measured EEG, cerebral blood flow (CBF), cerebral oxygen consumption (CMRO(2)) and cortical microdialysate levels of glutamate, aspartate and glycine in pentobarbital-anesthetized piglets during 60 min of insulin-induced hypoglycemic coma. NMDA-receptor distribution was measured by autoradiography. MK801 (0.75 mg/kg i.v.) was given within 5 min after onset of isoelectric EEG. Saline- and MK801-treated normoglycemic control animals were also studied. Brain temperature was maintained at 38.5+/-0.5 degrees C. MK801 prevented the 5--10-fold increase in glutamate and aspartate occurring in saline-treated hypoglycemic animals, and attenuated the increase in CMRO(2). Increases in CBF of 200--400% during hypoglycemic coma were not affected by MK801. MK801 did not alter CBF, CMRO(2) or microdialysate amino acid levels in normoglycemic control animals. Parietal cortex corresponding to microdialysis sites was highly enriched in NMDA receptors, and the density and distribution overall of NMDA receptor binding sites were comparable to that reported in other species. We conclude that NMDA receptor activation plays a central role in hypoglycemia-induced glutamate release, and contributes to increased cerebral oxygen consumption. Neuroprotective effects of MK801 during hypoglycemia in piglets may involve inhibitory effects on glutamate release and oxidative metabolism.
Volume
128
Issue
2
First Page
139
Last Page
148
ISSN
0165-3806
Published In/Presented At
Ichord, R. N., Johnston, M. V., & Traystman, R. J. (2001). MK801 decreases glutamate release and oxidative metabolism during hypoglycemic coma in piglets. Brain research. Developmental brain research, 128(2), 139–148. https://doi.org/10.1016/s0165-3806(01)00161-4
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
11412899
Department(s)
Department of Pediatrics
Document Type
Article