N-methyl-D-aspartate receptors mediate post-traumatic increases of protein kinase C in rat brain.
Male Sprague-Dawley rats were subjected to traumatic brain injury (TBI) using a lateral fluid percussion-induced injury model. Effects of varying severities of TBI (mild = 1.1 +/- 0.1 atm; moderate = 2.2 +/- 0.2 atm; severe = 2.9 +/- 0.1 atm) on the levels of protein kinase C in rat cerebral cortex and hippocampus were investigated by quantitative autoradiography using [3H]phorboldibutyrate ester ([3H]PDBu) binding as a marker. Binding of [3H]PDBu in the cerebral cortex and hippocampus was increased bilaterally following TBI, with changes related to injury severity. Significant increases were observed in hippocampus of injured animals, as compared to sham-operated controls, at 1 h after trauma. Maximum levels of binding in both cerebral cortex and hippocampus were reached by 3 h, with a return to control levels at 6 h and 72 h, respectively. Treatment with MK-801 (1 mg/kg, i.v.) administered 15 min before trauma prevented the injury-induced increase of [3H]PDBu binding in hippocampus and cerebral cortex. These results demonstrate that TBI induces bilateral, time-dependent increases of protein kinase C in the hippocampus and cerebral cortex that are related to injury severity. Changes are mediated by actions at NMDA receptors, probably reflecting post-traumatic release of glutamate.
Department of Neurology, Georgetown University School of Medicine, Washington, DC 20007.
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D000818:Animals; D001345:Autoradiography; D001930:Brain Injuries / Q000201:enzymology*; D002245:Carbon Dioxide / Q000097:blood; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D007839:Functional Laterality; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012016:Reference Values; D013997:Time Factors; D014316:Tritium
D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D002245:Carbon Dioxide; D015240:Phorbol 12,13-Dibutyrate; D016291:Dizocilpine Maleate; D011493:Protein Kinase C; D010100:Oxygen