Global and Cerebral Ischemia in Trangenic Mice

Morbidity and mortality in patients successfully resuscitated from cardiac arrest largely depends on recovery of neurological functions. In attempting to reduce the neurologic morbidity associated with cardiopulmonary resuscitation, it is important to discover the mechanisms involved in tissue injury and repair. The use of transgenic mice models allows us to investigate the contribution of various gene products to brain injury. In a new model of cardiac arrest and cardiopulmonary resuscitation we will examine the importance of oxygen radicals using mice with overexpression of superoxide dismutase, neuronal nitric oxide synthase knockout mice and double transgenic mice. In another study we will investigate the role of DNA repair mechanisms after ischemic brain injury using poly(ADP-ribose) polymerase knockout mice. A novel therapeutic approach to treat various disorders of the central nervous system is transplantation of neural stem cells. Using our new cardiac arrest model we will investigate if transplanted cells survive and differentiate into neurons, and if animals receiving neural stem cells show a better recovery of neurological functions when compared to saline treated controls.