Long-term behavioral and ultrastructural alterations following hypoxic-ischemic brain damage in neonatal rats

Objective To study long-term behavioral and ultrastructural alterations in a hypoxic-ischemic brain damage(HIBD) model of neonatal rats.Methods Sixty seven-day-old Sprague-Dawley rats were randomly subjected to unilateral carotid artery ligation followed by hypoxic exposure(HIBD group) or sham operation(n=30 each).A battery of behavioral tests,including Morris water maze test and sensorimotor tests,were performed at a postnatal age of 5 weeks.Nissl staining was used for counting neurons.Transmission electron microscopy was used for observing synapse structures and measuring the thickness of the postsynaptic density area and the length of the postsynaptic active area.The correlations of histological changes with the results of behavioral tests were evaluated.Results The HIBD group showed a significantly longer escape latency(P0.05) and a lower frequency of original platform crossing(P 0.05) in the Morris water maze test compared with the sham operation group.The sensorimotor function test showed that the sensorimotor function in the HIBD group was worse than in the sham operation group.Nissl staining showed that the number of neurons in the HIBD group was significantly reduced(P 0.01) compared with the sham operation group.Transmission electron microscopy showed that synapses were significantly reduced in number,and that the thickness of the postsynaptic density area and the length of the postsynaptic active area were reduced in the HIBD group.The thickness of the postsynaptic density area was negatively correlated with escape latency in the Morris water maze test(r=-0.861,P0.01),and also negatively correlated with the total score of sensorimotor function tests(r=-0.758,P0.05) in the HIBD group.Conclusions Hypoxia ischemia can lead to neuron loss and ultrastructure damage,resulting in long-term deficit of behavioral functions in neonatal rats.