A new model of neonatal stroke: Reversible middle cerebral artery occlusion in the rat pup

Neonatal stroke remains a complex pathophysiologic process that is poorly understood and difficult to investigate. The primary animal model used to study this phenomenon is that of unilateral carotid artery ligation with 2-3 hours exposure to severe hypoxia. A new model of neonatal stroke was developed based on transient middle cerebral artery occlusion without craniectomy. In this model a #6-0 (0.07 mm) nylon filament is passed via the carotid artery to occlude reversibly the middle cerebral artery for 4 hours under conditions of normoxia in 14- to 18-day-old spontaneously hypertensive rat pups. After removal of the filament and reperfusion for 24 hours, the infarct volume was determined using the mitochondrial stain, 2,3,5-triphenyltetrazolium chloride. Using this technique, a neocortical and caudoputamenal infarct affecting 49% of hemispheric volume that measured 180 ± 29 mm³ (hemisphere volume = 359 ± 16 mm³, mean ± SEM) was created in 90% of animals (n = 8) undergoing this procedure. This model has the advantage of being relatively non-invasive, of not requiring global exposure of brain to hypoxia, and of using temporary rather than permanent occlusion. This technique should improve the ability to study the acute and long-term pathophysiology of neonatal stroke, particularly the phenomenon of reperfusion injury, as well as its sequelae in the developing nervous system.