EFFECT OF NEUROPROTECTIVE N-METHYL-D-ASPARTATE ANTAGONISTS ON INCREASED INTRACRANIAL-PRESSURE - STUDIES IN THE RAT ACUTE SUBDURAL-HEMATOMA MODEL

Glutamate antagonists are the most powerful neuroprotective drugs in l aboratory studies of focal cerebral ischemia. Because the majority of clinical conditions in which focal brain ischemia occurs are associate d with high intracranial pressure (ICP), we have used the rat acute su bdural hematoma model to evaluate the effects of three glutamate N-met hyl-D-aspartate antagonists, MK-801, CGS 19755 (SELFOTEL), D-CPP-ene, and mannitol, upon ICP and also upon the volume of ischemic brain dama ge. Only mannitol produced a significant reduction in ICP and improved cerebral perfusion pressure. The three glutamate antagonists did not significantly affect ICP or cerebral perfusion pressure, but they were associated with a significantly smaller zone of focal brain damage, w hen compared to the mannitol and saline groups. N-methyl-D-aspartate a ntagonists do not increase ICP or jeopardize cerebral perfusion pressu re when administered under anesthesia with a controlled PaCO2 level. F urther studies in humans are indicated.