Pharmacologic therapy: promising clinical investigations

The identification of ischemia as a central mechanism of cell injury within the nervous system has resulted in a commonality of interests of neurosurgeons, neurologists and basic scientists interested in head injury, subarachnoid hemorrhage and stroke. This, in turn, has led to a certain synergy between the development of new agents and the availability of interested and committed investigators so that these agents can be tested under appropriate clinical conditions. In head injury, major sources of focus have been the membrane damage resulting from the free-radical cascade and the disruption in cellular ionic homeostasis resulting from the excitotoxic effects of pathologic release of amino acid neurotransmitters. At present, the final analyses of phase III trials of the antagonism of the initiation and propagation of the free-radical cascade by tirilazad and polyethylene glycol-bound superoxide dismutase are nearing completion. Data on the efficacy of these agents in improving outcome from moderate and severe head injury should be available within the next 6 months. In addition, worldwide trials of glutamate antagonists are presently being initiated in severe head injury, with results anticipated in late 1997 or early 1998. In subarachnoid hemorrhage, calcium has been hypothesized to play a role in mediating vasospasm-induced ischemia as well as in promoting intracellular damage. Trials of calcium-channel blockade have demonstrated a reduction in mortality, but no improvement in the quality of survival over other methods of managing these patients.(ABSTRACT TRUNCATED AT 250 WORDS)