Pharmacologic Neuroprotection

Considerable progress has been made in the understanding of the consequences of brain anoxia/ischaemia and reperfusion on metabolism and neuronal viability. Neurons are particularly susceptible to ischemic injury because they have a higher demand for energy and limited energy stores that get depleted within 2 to 4 minutes of anoxia. Neuroprotection involves provision of the means to prevent or minimize injury to neurons using treatments used to protect neural tissue from cellular events induced by deprivation of oxygen or glucose or both to the brain. . When confronted with the need for neuroprotection, a clear understanding of the underlying mechanisms of both injury and treatment are required to decide on the best approach. Neuronal tissue injury processes continue over a prolonged period of time, implying that neuroprotective therapies may be initiated beyond the acute post-injury phase. Drugs targeting prolonged injury mechanisms, such as mitochondrial dysfunction, axonal injury, and neuro inflammation have a better chance of limiting irreversible damage. Barbiturates, etomidate, propofol, isoflurane, methylprednisolone, tirilazad mesylate, nimodipine, nicardipine and mannitol have all been used for neuroprotection, combining physiologic (oxygen, hypothermia), pharmacologic (erythopoietin derivatives), thrombolytic and anesthetic therapies. The concept of an ischemic penumbra and the chemical brain retractor concept have aided the emergence of neuroprotective strategies that play important roles in perioperative situations such as cardiopulmonary bypass, deep hypothermic circulatory arrest, carotid surgery, and cerebral aneurysm surgery. Pharmacological neuroprotection is also exhibited in subarachnoid haemorrhage, stroke, brain trauma, spinal trauma, induced hypotension, and post cardiac arrest resuscitation. Important strategies in neuroprotection include maintenance of normoxia, adequate cerebral perfusion pressure, maintenance of mild hypothermia