Stroke is among the most common neurological disorders in the US. Most strokes involve a blockage of one of the blood vessels of the brain, thus depriving a region of brain tissue of its much needed oxygen and nutrients. In many cases, at least some blood flow is restored (reperfusion). Whereas restoration of blood flow sounds very positive, unfortunately providing significant levels of oxygen to a compromised tissue can also lead to the generation of reactive oxygen species. Both of the damaging aspects of the two main components of stroke - acute ischemia and reperfusion - have been reproduced in adult rat models, and the pathways and mechanisms of damage are beginning to emerge. Several observations suggest that the neonatal brain is more tolerant to ischemic events than the adult brain. Most current ischemia research in neonates is focused on the hypoxia associated with child birth and these models lack the reperfusion component studied in stroke. Ischemic strokes in infants and children are rare compared to strokes in adults, yet they do occur and are probably under diagnosed. When strokes occur in children they are frequently in the same brain regions as in adults. Our studies will examine important basic mechanisms of brain damage in an infant rat model of transient focal ischemia with reperfusion. We will determine the presence, sources and persistence of several known mediators of ischemic damage, namely: excitatory amino acids, immediate early genes, and hydroxyl radical. Our studies will focus on the mechanisms that regulate the levels of these mediators and the interactions between and among them. We will also investigate the changes that occur in various regions of the infarct - the core, the penumbra and the extra-penumbra areas. Understanding how these mediators are regulated in the infant brain will provide insights into the differences in ischemic responses in the infant and the adult, and will promote rational treatment of both juvenile and adult ischemic events.
| Pabello, Nina G; Tracy, Seth J; Keller Jr, Richard W (2004) Protective effects of brief intra- and delayed postischemic hypothermia in a transient focal ischemia model in the neonatal rat. Brain Res 995:29-38 |
