Opportunities for neuroprotective drugs in clinical management of head injury.

Over the past 15 years, neuropathological studies, patient monitoring, and data emerging from the laboratory have significantly advanced the understanding of both primary and secondary brain damage. The challenge now rests with the clinician treating head injury, who must translate these recent developments into real benefits for the patient. Neurological deterioration after head injury may be due to the effects of secondary mechanisms in up to one-third of cases. These secondary events may follow early insults such as transient global ischemia, hematomas, or diffuse axonal injury. They may be mediated by complex cascades of biochemical processes. Many of these secondary posttraumatic events have been targeted as potential sites for pharmacological intervention. In models of focal brain ischemia, a new generation of compounds that inhibit activity of glutamate has been shown to ameliorate the severity of the ischemic insult. Other potential neuroprotective agents that are currently being clinically investigated include free radical scavengers and calcium antagonists. Preliminary findings show indications of improved neurological outcome with early administration of a number of these drugs. Because head-injured patients tend to be admitted to the hospital within hours of injury, which allows for pretreatment or early therapy, several ongoing trials are assessing safety, tolerance, and efficacy of many new therapeutic agents combined with standard management. It is hoped that the outcome of this novel approach to head injury management will be positive and will help to reduce the high morbidity and mortality associated with head injuries.