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.