Role of Synaptic Transmission Failure in the Neurologic Deficit of Ischemic Brain Injury
The successful care, treatment and prognosis of patients suffering cerebral insults depend upon a thorough understanding of the factors and mechanisms leading to the ultimate neurologic deficit. Past studies have revealed several major facets in the pathogenesis of cerebral ischemicanoxic injury. First, the degree of the neurologic deficit sustained depends upon not only the initial insult but also the pathological processes developing post-insult that aggravate and extend the injury. These are among others the no-reflow phenomenon, delayed postischemic hypo-perfusion and hypermetabolism, free-radical generation, and lipid peroxidation. Second, the degree of the neurologic deficit sustained may be attributable not only to irreversible neuronal necrosis, but also to a — possibly reversible — failure of synaptic transmission without failure of oxidative phosphorylation. Finally, most recent studies suggest that the evolution of ischemic brain damage may be related to a release of free fatty acids (FFA) from membrane phospholipids (PL). Membrane PLs are likely to be involved in membrane transduction processes of synaptic transmission, namely channel gating, membrane-bound enzyme activities, such as adenylate cyclase, phosphodiesterases, and receptor sensitivity. Our intent is to present evidence that failure of synaptic transmission could contribute to the neurologic dysfunction of ischemic brain injury.
KeywordsSynaptic Transmission Adenylate Cyclase Ischemic Brain Injury Ischemic Brain Damage Respiratory Control Ratio
Unable to display preview. Download preview PDF.
- 1.Hinzen DH, Müller U, Sobotka P, Genert E, Lang R, Hirsch H, Metabolism and function of dog’s brain recovering from longtime ischemia, Am J Physiol 223: 1158 (1972).Google Scholar
- 4.Glick SD, Zimmerberg B, Pharmacological modification of brain lesion syndromes, in: “Recovery from brain damage, research and theory”, Finger S, ed., Plenum Press, New York (1978).Google Scholar
- 7.Siesjö BK, Brain energy metabolism, John Wiley & Sons, New York (1978).Google Scholar
- 8.Grossman RG, Williams V, Electrical activity and ultrastructure of cortical neurons and synapses in ischemia, in: “Brain hypoxia”, Brierley JB, Meldrum BS, Lippincott JP, Lippincott Co., Philadelphia (1971).Google Scholar
- 13.Kogure K, Scheinberg P, Kishikawa H, Busto R, The role of monoamines and cyclic AMP in ischemic brain edema, in: “Dynamics of brain edema”, Pappius HM, Feindel W, eds., Springer-Verlag, Berlin (1976).Google Scholar
- 14.Strang RHC, Estimation of Km values of enzymes requiring molecular 0, as a substrate, Biochem J Letters 193: 1033 (1981).Google Scholar
- 17.Lin MR, Nemoto EM, Kessler PD, Alterations in whole brain cyclic-AMP and cerebral cortex NA-inducible cyclic-AMP in rats during and after complete global ischemia, in: “Brain protection-morphological, pathophysiological and clinical aspects”, Wiedemann K, Hoyer S, eds., Springer Verlag, New York (1983).Google Scholar
- 19.Strong AJ, Tomlinson BE, Venables GS, Gibson G, Hardy JA, The cortical ischaemic penumbra associated with occlusion of the middle cerebral artery in the cat: 2. Studies of histopathology, water content, and in vitro neurotransmitter uptake, J Cerebral Blood Flow Metab 3: 97 (1983).CrossRefGoogle Scholar
- 24.Berridge MJ, A novel cellular signaling system based on the integration of phospholipid and calcium metabolism, in: “Calcium and cell function”, Cheung WU, ed., Academic Press, New York (1983).Google Scholar