Effects of exogenous ganglioside-1 on learning and memory in a neonatal rat model of hypoxia-ischemia brain injury

BACKGROUND:Exogenous ganglioside-1(GM1) can cross the blood-brain barrier and play a protective role against hypoxia-ischemia-induced brain damage.OBJECTIVE:To examine the possible mechanisms of exogenous GM1 protection in hypoxia-ischemia-induced brain damage in a neonatal rat model by measuring changes in brain mass,pathological morphology,growth-associated protein-43 expression,and neurobehavioral manifestations.DESIGN,TIME AND SETTING:A randomized block-design study was performed at the Immunohistochemistry Laboratory of the Pediatric Research Institute,Children’s Hospital of Chongqing Medical University from August 2005 to August 2006.MATERIALS:A total of 36 neonatal,7-day-old,Sprague Dawley rats were used in this experiment.The hypoxia-ischemia-induced brain damage model was established by permanently occluding the right carotid artery,followed by oxygen inhalation at a low concentration(8% O2,92% N2) for 2 hours.METHODS:All rats were randomly divided into the following groups:GM1,model,and sham operation,with 12 rats each group.Rats in the GM1 and model groups received hypoxic/ischemic-induced brain damage.Rats in the GM1 group received injections of GM1(i.p.,20 mg/kg) at 0,24,48,72,96,120,and 144 hours following models established,and rats in the model group were administered(i.p.) the same amount of saline.The right carotid artery was separated,but not ligated,in the sham operation group rats.MAIN OUTCOME MEASURES:At 1 week after surgery,expression of growth-associated protein-43,a marker of neural development and plasticity,was detected in the hippocampal CA3 region by immunohistochemistry.Brain mass was measured,and the pathological morphology was observed.At 4 weeks after surgery,behavioral changes in the remaining rats were tested by Morris water maze,and growth-associated protein-43 expression was measured.RESULTS:(1) In the GM1 and sham operation groups,growth-associated protein-43 expression was greater in the hippocampal CA3 region compared to the model group 1 week after surgery(P < 0.05).In all three groups,brain weight of the right hemisphere was significantly less than the left hemisphere,in particular in the model group(P < 0.05).In the GM1 group,the weight difference between two hemispheres,as well as the extent of damage in the right hemisphere,was less than the model group(P < 0.01).In the sham operation group,brain tissue consisted of integrated structures and ordered cells.In the model group,the cerebral cortex layers of the right hemisphere were not defined,neurons were damaged,and neurons were disarranged in the hippocampal area.In the GM1 group,neurons were dense in the right cerebral cortex and hippocampal area,with no significant change in glial proliferation.(2) The average time of escape latency in the GM1 group was shortened 4 weeks after surgery,and significantly less than the model group(P < 0.05).In addition,the frequency platform passing in the GM1 group was significantly greater than the model group(P < 0.01).CONCLUSION:Exogenous GM1 may reduce brain injury and improve learning and memory in hypoxia-ischemia-induced brain damage rats.This protection may be associated with increased growth-associated protein-43 expression,which is involved in neuronal remodeling processes.