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 widespread 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-asparate (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 (20mg/kg/day), a 5-HT2 receptor blocker ameliorated the depression of glucose utilization in traumatized brain while MK-801 (3mg/kg, before and after lesion), an NMDA receptor blocker, had no effect. Alpha1-adrenergic receptors, quantitated in vivo with [125I]-HEAT (iodo-2-[β-(4-hydroxyphenyl)-ethyl-aminomethyl]tetralone), were found to be elevated in cortical areas of the lesioned hemisphere, but not in other structures.
KeywordsBiogenic Amine Quinolinic Acid Cereb Blood Flow Injured Brain Functional Disturbance
Unable to display preview. Download preview PDF.
- Heyes MP, Markey SP (1988) Quantification of quinolinic acid in rat brain, whole blood, and plasma by gas chromatography and negative chemical ionization mass spectro-metry: effects of systemic L-tryptophan administration on brain and blood quinolinic acid concentrations. Anal Biochem 174: 349–359.PubMedCrossRefGoogle Scholar
- Pappius HM (1985) The continuing search for mechanisms underlying functional disturbances in traumatized brain. In: Inaba Y, Klatzo I, Spatz M (eds) Brain edema. Proceedings of the Sixth International Symposium on Brain Edema, Tokyo, Japan. Springer, Berlin Heidelberg New York Tokyo, pp 286–293.Google Scholar
- Pappius HM, Dadoun R (1986) Biogenic amines in injured brain. Trans Am Soc Neurochem 17: 298.Google Scholar
- Pappius HM, Wolfe LS (1983b) Involvement of serotonin and catecholamines in functional depression of traumatized brain. J Cereb Blood Flow Metab 3 [Suppl 1]: 226–227.Google Scholar
- Pappius HM, Wolfe LS (1984) Effects of drugs on local cerebral glucose utilization in traumatized brain: mechanisms of action of steroids revisited. In: Go G, Baethmann A (eds) Recent progress in the study and therapy of brain edema. Proceedings of the Fifth International Symposium on Brain Edema, Groningen, The Netherlands. Plenum Press, New York, pp 11–26.Google Scholar
- Pappius HM, Wolfe LS (1986) Neurochemical sequelae of brain damage and their role in functional disturbances. In: Baethmann A, Go KG, Unterberg (eds) Mechanisms of secondary brain damage. Proceedings of a NATO Advanced Research Workshop, Mauls/Sterzing, Italy. Plenum Press, New York, pp 151–167.Google Scholar
- Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The (14C)deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897–916.PubMedCrossRefGoogle Scholar
- Van Nueten JM, Janssen AJ, Van Beek J, Xhonneux R, Verbeuren TJ, Vanhoutte PM (1981) Vascular effects of ketanserin (R 41468), a novel antagonist of 5-HT2 serotonergic receptors. J Pharm Exper Ther 218: 217–230.Google Scholar
- Weiner N (1980) Drugs that inhibit adrenergic nerves and block adrenergic receptors. In: Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics, 6th edn. Macmillan, New York, pp 176–205.Google Scholar