title: Brain injury: new insights into neurotransmitter and receptor mechanisms.
abstract: The studies reviewed here represent a continuing search for mechanisms which play a role in neurological disturbances resulting from brain injury. Focal cortical freezing lesions in rats were shown to cause a widespread decrease in local cerebral glucose utilization (LCGU) in cortical areas of the lesioned hemisphere and this was interpreted as reflecting a depression of cortical activity. Such an interpretation was supported by the finding that in lesioned brain reduction of cerebral metabolism by pentobarbital and isoflurane was limited by the metabolic depression that has already occurred as a result of injury and by the demonstration that the energy status and substrate (glucose) supply in the cortical areas in the injured brain have not been compromised at the time when LCGU was decreased. Both the serotonergic and the noradrenergic neurotransmitter systems were implicated in functional alterations associated with injury. Cortical serotonin (5-HT) metabolism was increased throughout the lesioned hemisphere and complete inhibition of 5-HT synthesis with p-chlorophenylalanine ameliorated the decrease in cortical LCGU, interpreted as reflecting cortical functional depression. Cortical norepinephrine metabolism was bilaterally increased in focally injured brain, while prazosin, a selective alpha 1-noradrenergic receptor blocker, normalized cortical LCGU in the lesioned hemisphere. Low-affinity in vivo binding of [125I]HEAT, another selective alpha 1-receptor ligand, was specifically increased in cortical areas of the lesioned hemisphere at the time of the greatest depression in LCGU, suggesting that alpha 1-adrenoreceptors may be of functional importance in injured brain.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Goad Unit, Montreal Neurological Institute McGill University, Montreal, Quebec, Canada.
authors.forename: H M
authors.initials: HM
authors.lastname: Pappius
mesh_terms: D019325:3-O-Methylglucose; D000818:Animals; D001345:Autoradiography; D001679:Biogenic Amines / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D003847:Deoxyglucose; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D001679:Biogenic Amines; D008757:Methylglucosides; D011942:Receptors, Adrenergic, alpha; D019325:3-O-Methylglucose; D012701:Serotonin; D003847:Deoxyglucose; D005947:Glucose; D009638:Norepinephrine