Inhibition of neurogenic inflammation as a novel treatment for ischemic stroke.

Abstract

Each year, 15 million people suffer a stroke, of which 5 million die and 5 million are left permanently disabled. Cerebral swelling is of particular concern following stroke as it accounts for much of the death and disability. However, the mechanisms leading to cerebral swelling are not yet fully understood. Recent studies from our laboratory suggest that neuropeptides, and specifically substance P, may be involved in the injury processes that occur following acute insults to the brain such as stroke and trauma, and may be responsible, in part, for edema formation. Levels of substance P are increased following CNS injury, indicative of neurogenic inflammation, and this is associated with injury to the blood-brain barrier, the development of cerebral edema, cell death and functional deficits. Subsequent studies inhibiting neuropeptide release have consistently shown decreased cerebral edema and improved neurological outcome, while substance P antagonists administered after the insult are efficacious in reducing post-stroke cerebral edema and neurological deficits. The current review summarizes the evidence supporting the benefits of inhibiting neurogenic inflammation to treat ischemic stroke.