Excerpt from Neuroprotective Agents in Stroke

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Stroke is the third leading cause of death in the United States and the most common cause of adult disability. An ischemic stroke occurs when a cerebral vessel occludes, obstructing blood flow to a portion of the brain.

The only currently approved medical stroke therapy, tissue plasminogen activator (tPA), is a thrombolytic that targets the thrombus within the blood vessel. Neuroprotective agents, another approach to stroke treatment, have generated as much interest as thrombolytic therapies.

Using various mechanisms, neuroprotective agents attempt to save ischemic neurons in the brain from irreversible injury. Studies in animals indicate a period of at least 4 hours after onset of complete ischemia in which many potentially viable neurons exist in the ischemic penumbra. In humans, the ischemia may be less complete, and the time window may be longer, but human patients also tend to be older with comorbidities that may limit benefit. As many neuroprotective drugs reduce ischemic damage in animal models of stroke, this line of pharmaceutical research holds great promise. Many are searching for a safe agent that can limit ischemic damage in human stroke.

One action of neuroprotective agents limits acute injury to neurons in the penumbra region or rim of the infarct after ischemia. Neurons in the penumbra are less likely to suffer irreversible injury at early time points than are neurons in the infarct core. Many of these agents modulate neuronal receptors to reduce release of excitatory neurotransmitters, which contribute to early neuronal injury.

Other neuroprotective agents prevent potentially detrimental events associated with return of blood flow. Although return of blood flow to the brain is generally associated with improved outcome, reperfusion may contribute to additional brain injury. Returning blood contains leukocytes that may occlude small vessels and release toxic products.

This article discusses 2 types of neuroprotective agents, one that prevents early ischemic injury and another that prevents reperfusion injury. Clinical trial results of these agents are summarized.

For excellent patient education resources, visit eMedicine's Stroke Center. Also, see eMedicine's patient education article Stroke.

Please click here to view the full topic text: Neuroprotective Agents in Stroke