Long-lasting behavioral alterations following a hypoxic/ischemic brain injury in neonatal rats

The characterization of motor and cognitive dysfunctions following a neonatal ischemic injury is a prerequisite to investigate putative pharmacological interventions. To this end, in the present study, we evaluated the long-lasting behavioral alterations occurring after a hypoxic/ischemic injury obtained by the combination of monolateral carotid ligation and exposure to 8% oxygen for 3 h in 7-day-old rats. These animals show a different degree of damage in the side ipsilateral to the occluded artery. Motor coordination, tested both before and after weaning, was not affected, whereas spontaneous activity was increased at weaning but not in the adult age. When tested in an open field after apomorphine administration, most ischemic animals showed a marked turning behavior ipsilateral to the lesioned side. They also had a reduced rate of spontaneous alternation and a marked tendency to visit the arm of the T-maze ipsilateral to the lesion. Injured rats were deficient in performing water maze and T-maze acquisition tests but, when evaluated in a passive avoidance paradigm, no difference from controls was observed. These data indicate that an ischemic insult in neonatal rats causes long-lasting learning deficits and motor behavior asymmetry. These behavioral alterations may represent a useful endpoint for studying the efficacy of potential pharmacological treatments that may improve the behavioral consequences of a perinatal hypoxic/ischemic insult in humans.