Neurochemical approaches to the amelioration of brain injury.
The studies reported here represent a continuing search for mechanisms which may play a role in neurological disturbances resulting from brain injury. In particular, they are part of an effort to elucidate the involvement of both the serotonergic and noradrenergic neurotransmitter systems in the wide-spread decrease in cortical glucose utilization, interpreted as reflecting a functional depression, associated with a focal cortical lesion in the rat. Quinolinic acid, an endogenous metabolite of L-tryptophan, a neurotoxin and an N-methyl-D-aspartate (NMDA) receptor agonist was found to accumulate in cortical areas of a traumatized rat hemisphere in parallel with a previously demonstrated increase of 5-hydroxyindoleacetic acid. Ketanserin (20 mg/kg/day), a 5-HT2 receptor blocker ameliorated the depression of glucose utilization in traumatized brain while MK-801 (3 mg/kg, before and after lesion), an NMDA receptor blocker, had no effect. Alpha 1-adrenergic receptors, quantitated in vivo with [125I]-HEAT (iodo-2-[beta-(4-hydroxyphenyl)-ethyl-aminomethyl]tetralone), were found to be elevated in cortical areas of the lesioned hemisphere, but not in other structures.
Donner Laboratory of Experimental Neurochemistry, Montreal Neurological Institute, McGill University, Quebec, Canada.
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Pappius
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007213:Indomethacin / Q000627:therapeutic use*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D011224:Prazosin / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*
D001095:Arachidonic Acids; D003986:Dibenzocycloheptenes; D011942:Receptors, Adrenergic, alpha; D016718:Arachidonic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D016291:Dizocilpine Maleate; D007650:Ketanserin; D003847:Deoxyglucose; D011224:Prazosin; D007213:Indomethacin