FROM THE BENCH TO THE BEDSIDE - THE MOLECULAR MANAGEMENT OF CEREBRAL-ISCHEMIA

Rapid and accurate management of a patient afflicted by cerebral ische mia is crucial for the development of a successful outcome. Yet, it is the understanding of the molecular and clinical presentation of cereb rovascular disease that enables the physician to diagnose and effectiv ely treat cerebral ischemia. Neuronal degeneration can occur at severa l levels in the ischemic cascade. The free radical nitric oxide (NO) h as been clearly linked to ischemic neurodegeneration in both animal mo dels and cell culture systems, but the final cellular pathways that le ad from the generation of NO to eventual neuronal death require furthe r investigation. The protective mechanisms of the peptide growth facto rs basic fibroblast growth factor and epidermal growth factor appear t o be linked to the signal transduction pathways of NO, programmed cell death, and protein kinase C. Active modulation of metabotropic glutam ate receptor activity also can prevent neuronal injury at or below the level of NO generation. The molecular mechanisms that mediate the pro tective effects of the metabotropic glutamate receptors are dependent on the modulation of programmed cell death. Further investigation into the molecular signal transduction pathways that are responsible for i schemic neuronal injury will foster the development of efficacious and safe treatments for cerebral ischemia.