Brain Metabolism, the Pathophysiology of Brain Injury, and Potential Beneficial Agents and Techniques

For cerebral ischemia, traumatic brain injury and epilepsy, ionic imbalance (particularly high intracellular calcium or sodium levels), and energy depletion have been implicated as triggers of brain damage. In neurons, subsequent to these pathophysiologic insults, molecular biological and biochemical changes are triggered, which can lead to either apoptotic or necrotic cell death. Thus, common mechanisms of neuronal cell death for various pathophysiologic events may exist. Thrombolysis is recommended for ischemic stroke if it can be instituted within 4.5 hours of onset; this treatment worsens hemorrhagic stroke, so accurate and rapid diagnosis is required. If there is an occlusion of a large cerebral artery, intraarterial mechanical thrombectomy has been shown to be of benefit compared to intravenous rtPA alone. Encouraging agents and procedures from animal studies such as hypothermia, very high-dose barbiturates, sevoflurane, sodium channel blockers, free radical scavengers, NMDA antagonists, calcium channel blockers, and antiapoptotic agents have not been shown to have clinical benefits and are not recommended. Anticonvulsant medications should be used to immediately arrest status epilepticus. Rapid reperfusion after ischemic stroke and prevention of seizures, hypoxia, hypoperfusion and hyperthermia during and after trauma, seizures, or cerebral ischemia are important measures that can improve long-term outcome. Thus, a number of treatments can be employed with some hope of reducing permanent brain damage.