Developing Gene-Based Neuroprotection Strategies Using Herpes Amplicon Vectors

Ischemia in the central nervous system produces a heterogeneous pattern of neuronal loss, which is dependent on the extent, duration, and distribution of vessel occlusion. Profound hypoperfusion produces neuronal necrosis in a matter of hour, resulting in plasma membrane rupture and subsequent release of synaptic and somal contents to the interstitial space. An appreciation for the role of elevated extracellular glutamate and intracellular calcium in this pathologic sequence has prompted the development of glutamate and calcium receptor antagonists. Unfortunately, these strategies have not produced in humans the degree of protection observed in animal models of acute necrotic stroke (Zivin and Miller 1999).