MECHANISM OF INJURY AND REPAIR IN ISCHEMIC STROKE

The onset of stroke is usually sudden, but the pathological processes
leading up to it and recovery from it are gradual. This renewal
application, "Mechanisms of Injury and Repair in Ischemic Stroke", focuses
on the humoral and cellular mediators of ischemic brain injury and repair.
The term "humoral mediator" connotes the long term effects of cytokines
hormones, and growth factors. In Project 1 the influence of chronic
hyperviscosity on recurrent stroke will be examined in a longitudinal
clinical study. This project will determine whether impaired glucose
tolerance and/or chronic release of interleukins 1 or 6 predisposes to
hyperviscosity. Project 2 will examine the influence of dexamethasone on
brain metabolism in ischemia using in vivo and in vitro models. A key
question to be addressed is whether dexamethasone increases glucose
transport into the brain, thereby aggravating brain lactic acidosis during
ischemia. Project 3 will use animal models of ischemia and molecular
biological techniques to investigate the role of acidic and base fibroblast
growth factors in central nervous system repair after ischemic injury. The
experiments proposed will study the regional distribution, cellular
sources, and biochemical signaling and production of these growth factors
in the brain. Project 4 will examine cellular mechanisms of nervous system
repair in the mouse cerebellar explant culture system. Studies in this
project will define the role of neuronal activity in neuronal-cellular and
neuronal-glia reorganization after injury. The proposed projects, focusing
on humoral and cellular modulators, range from molecular to clinical
neuroscience and offer potential therapeutic benefits for stroke
prevention, intervention, and rehabilitation.