Exercise Rehabilitation Training In Rats With Hypoxic-ischemic Brain Injury And Its Possible Mechanism Of Learning And Memory

PART I ESTABLISHMENT OF HYPOXIA-ISCHEMIA BRAIN DAMAGE MODEL IN NEONATAL RATSObjective To establish a successful hypoxic-ischemic brain injury model in neonatal rats.Methods Following Rice-Vannucci, thirty-two 7-day-old Sprague-Dawley rats were randomly divided into two groups: a group that was subjected to left carotid ligation followed by 2 hours hypoxic stress (HIBD) and a control group that was subjected to a sham-operation without ligation and hypoxic stress. Behavioral manners of rats were observed soon after hypoxic insult. Three developmental reflexes (righting, cliff aversion and geotaxis) of all rats were then assessed 24 hours later, after that 8 rats were randomly chosen from each group and their brains were prepared for TTC staining. Four weeks after the end of hypoxia, the remaining rats were decapitated and their brain slices were prepared for pathological examination.Results Rats in HIBD group had various kinds of abnormal behavioral performances after hypoxic injury, and they also showed delayed developmental reflexes compared with rats in control group. TTC staining showed that rats submitted to hypoxia suffered extensive cortical and subcortical (including hippocampus) cerebral infarcts ipsilateral to the ligated carotid artery, while rats in sham control group did not develop brain infarcts. In gross anatomic examination, cerebral atrophy accompanied with liquefaction and cavitation was noticed in the hemisphere of rats submitted to ipsilateral carotid artery ligation followed by hypoxia, and microscopic examination of the cerebral sections showed significant loss of neurons in hippocampus ipsilateral to the side of carotid artery ligation in hypoxia-ischemia affected rats; while no abnormality was observed in both gross anatomic and microscopic examination in rats subjected to a sham-operation.Conclusions A successful hypoxic-ischemic brain injury model in neonatal rats can be obtained following Rice-Vannucci. PART II PHYSICAL TRAINING TASKS IMPROVE SPATIAL LEARNING IMPAIRMENTS FOLLOWING HYPOXIC ISCHEMIC INSULT IN NEONATAL RATSObjective To investigate the effect of physical training on cerebral structure and spatial learning and memory in neonatal rats submitted to hypoxic-ischemic brain damage (HIBD).Methods Forty-eight 7-day-old Sprague-Dawley rats were randomly divided into three groups: a group that was subjected to left carotid ligation followed by 2 hours hypoxic stress (HIBD), a group that received physical training 2 weeks after the HIBD event and a control group that was subjected to a sham-operation without ligation and hypoxic stress. After four weeks physical training, motor function test and water maze task were performed; thereafter, bilateral brain weight, cerebral morphology and left hippocampal ultrastructrue of the animals were examined. Finally, expression levels of phosphor calmodulin-dependent protein kinase II (CaMKII) and brain derived neurotrophic factor (BDNF) in left hippocampus of all rats were determined by immunohistochemistry.Results Compared with the rats in control group and trained-HIBD group, rats in non-trained HIBD group had a remarkable worse performance in both motor function assessment and Morris water maze test, whereas there was no significant difference between the rats in trained-HIBD and control groups in motor function assessment and spatial learning test. Left hemisphere weight and survival neurons in left hippocampal CA1 zone of rats in both HIBD groups decreased sharply compared with rats in control group and rats in non-trained HIBD group had a even more significant reduction. The ultrastructure of left hippocampus of rats in non-trained HIBD group was remarkably abnormal, while the left hippocampal ultrastructure of rats in trained HIBD and control group had no certain abnormality. At last, phosphor-CaMKII and BDNF expression level in left hippocampus of rats in trained HIBD group increased significantly compared with rats in the non-trained HIBD group.Conclusions Physical training can restrain brain damage and ameliorate the spatial learning and memory impairments of rats submitted to hypoxia-ischemia insult.