Hypoxia-Ischemia Induced Nigrostriatal System Damages and Motor Behavioral Changes in Neonatal Rat Brain

ABSTRACT

OBJECTIVE: To investigate hypoxia-ischemia induced nigrostriatal system damages and motor behavioral changes in the immature developing rat brain. METHOD: For establishment of hypoxia-ischemia (HI) injury, bilateral common carotid artery occlusion was performed permanently with bipolar electrocoagulation in the postnatal day 5 rats. And then rat pups were immediately subjected to hypoxic exposure (8% oxygen) at 37degrees C for 1 hour. The control group underwent sham operation and normoxic exposure. Brain injury including striatonigral system was examined. Motor behavioral changes were investigated at 2-, 4-, 6- and 8-week after HI injury using the Rota-rod test and the d-amphetamine-induced locomotor activity. RESULTS: HI-induced motor behavioral deficits showed from 2-week to 8-week after HI injury. In the Rota-rod test, HI group exhibited significantly shorter mean fall latencies as compared to the control group. The d-amphetamine-induced locomotor activity test at the same time point showed reduced locomotor activity in HI group. HI injury resulted in brain structural damages in hippocampus, dorsolateral region of striatum and substantia nigra, and decreases in tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra. There was no evidence of spontaneous recovery in the substantia nigra at the 8-week after injury. CONCLUSION: HI induced brain injury at neonatal period could result in persistent motor behavioral deficits in juvenile rats. Those deficits might be linked with structural damages including nigrostriatal dopaminergic system.