Zinc and Focal Cerebral Ischemia

Zipfel, Gregory

Abstract

There is a growing body of evidence that zinc may play a role in neuronal death following ischemic insults. A number of in vitro studies have demonstrated zinc toxicity on a variety of CNS cell types, and there is strong in vivo evidence that zinc plays an important role in the selective neuronal death of global ischemia. In addition, in vitro and in vivo studies suggest that zinc toxicity is preventable through the use of a zinc specific chelator (CaEDTA). I hypothesize that zinc may play a role in the injury following focal ischemia as well. The following three specific aims will address this hypothesis. First, it will be determined if zinc translocation into penumbral neurons destined to die occurs in a transient middle cerebral artery occlusion (MCAO) rat model. To accomplish this, we will utilize a zinc- specific fluorescent marker (TSQ) applied to brain sections obtained from rats who underwent transient MCAO. Second, it will be determined if zinc-specific chelation through an intravencular administration of CaEDTA will decrease infarct size in this same transient MCAO model. Third, it will be determined if this CaEDTA treatment for focal ischemia improves functional outcome scores utilizing two motor performance scoring systems. The above studies will further define zinc s role in ischemic neuronal injury and potentially show that novel zinc-directed therapeutic regimens should be applied to focal ischemia.