Ischaemic brain damage associated with tissue hypermetabolism in acute subdural haematoma: reduction by a glutamate antagonist.
Ischaemia results in elevated extracellular glutamate concentrations, and drugs which act at the N-methyl-D-aspartate sub-type of glutamate receptor have been shown to decrease ischaemic brain damage. Because almost all patients who die after severe head injury demonstrate ischaemic brain damage, and acute subdural haematoma (ASDH) is one of the commonest complications of severe head injury, we have studied this condition in a rat model. Using double-label autoradiography, we have measured the effects of ASDH on cerebral glucose utilization and cerebral blood flow (RCBF). Following ASDH, increased glucose utilisation was observed in some cortical and hippocampal structures, without concomitant increases in blood flow. Directly below the ASDH, blood flow and glucose utilization were profoundly reduced. Pre-treatment with D-CPP-ene, a competitive NMDA antagonist, resulted in amelioration of hypermetabolism induced by the ASDH. The results suggest that NMDA antagonists may prevent ischaemic brain damage after ASDH by reducing hypermetabolism, induced by glutamatergic mechanisms.
Inglis
F M
FM
University Department of Neurosurgery, Southern General Hospital, Glasgow.
Bullock
R
R
Chen
M H
MH
Graham
D I
DI
Miller
J D
JD
McCulloch
J
J
D000208:Acute Disease; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D001925:Brain Damage, Chronic / Q000209:etiology*; D002545:Brain Ischemia / Q000209:etiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D006408:Hematoma, Subdural / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494; D018698:Glutamic Acid