Animal models of neonatal stroke

Neonatal stroke occurs in approximately 1 in 4,000 to 1 in 10,000 newborns, and more than 80% involve the vascular territory supplied by the middle cerebral artery. Neonatal stroke is associated with many acquired and genetic prothrombotic factors, and follow-up studies indicate that as many as two thirds of neonates develop neurologic deficits. In the past two decades unilateral carotid occlusion with 8% hypoxia has been used to study focal and global ischemia in the newborn, and recently a filament model of middle cerebral artery occlusion has been developed. This review describes the results of studies in these two newborn models covering aspects of the injury cascade that occurs after focal ischemia. A likely requirement is that therapeutic efforts be directed less at using thrombolytic therapy and more toward treatment of events associated with reperfusion injury, the inflammatory cascade, and apoptosis. Additional areas of research that have received attention in the past year include inhibition of nitric oxide and free-radical formation, use of iron chelating agents, the potential role of hypoxia-inducible factors and mediators of caspase activity, use of growth factors, hypothermia, and administration of magnesium sulfate.