| BackgroundTraumatic brain injury(TBI)is one of the main factors of death and disability in young adults,which is a common accident in all kinds of war and non war military operations and their daily life.A lot of traumatic brain injury patients injured even if the sensory motor function recovery,it may gradually appear to varying degrees of cognitive dysfunction;And a history of brain injury has been considered a risk factor for Alzheimer's disease.About 65% of medium to heavy traumatic brain injury and 15% of mild traumatic brain injury patients shown long-term cognitive problems;cognitive dysfunction is the main cause of disability in traumatic brain injury.At present,more basic research for the pathophysiological changes of traumatic brain injury are needed;and how to improve the cognitive impairment after traumatic brain injury was still absence.So the study has important practical significance.ObjectiveThis research is based on the animal model of rats,to reveal the effects of repeated mild traumatic brain injury and moderate traumatic brain injury with subarachnoid hemorrhage(SAH)on brain structure and cognitive behavioral function,and preliminary to compare the effects of nimodipine and deferoxamine on medium TBI patients with SAH.Method1.Using the weight drop method,the rat model of repeated mild TBI has been established.Based on improving the two hemorrhage SAH rat model,we established a rat model of moderate TBI with SAH.2.We evaluated the basic neural function such as motor,sensory,reflex and learning,memory and other advanced cognitive functions by behavioral research methods.The main tool for the evaluation were the modified nerve function loss scale score scale(m NSS)and Morris water maze test(MWM).3.7.0T high field strength small animal MR was used in vivo dynamic observation of changes in brain anatomy.The main imaging methods included T2 weighted imaging,diffusion tensor imaging(DTI),and magnetic resonance imaging and reconstruction(MRA).4.Preliminary pathology and molecular biology experimental were performed to observe the expression of neuronal cell loss and A?,ferritin,iron transport protein.5.In the drug intervention study,the effects of nimodipine and deferoxamine on the moderate TBI rats with SAH were compared.Result1.In the repeated closed mild TBI group,from the fifth impact,the recovery time of rats after impact was significantly prolonged with the increasing number of impact(P < 0.05).In the condition of no difference in the swimming ability,the rats in the repeated mild TBI group performed significantly worse in working memory tasks,probe trail and reference memory test than the control group and single mild TBI group(P < 0.05).2.In the repeated mild TBI group,a significant but reversible DTI was changed in the cerebral cortex,hippocampus and cingulated gyrus,where were the gray and white matter regions of the brain.Brain structures showed the gradual atrophy of the cortex and hippocampus and the expansion of the ventricles in repeated mild TBI group,which had significant statistical difference compared with the sham injury group and the single injury group(P < 0.01).3.The results of pathological study indicated that the nerve cells in the atrophy brain area of the experimental group were significantly lost(P < 0.05).4.The blood was mainly distributed in the basal cistern and the major vascular impression in the modified rat SAH model of double blood injection;and the basilar artery,middle cerebral artery and anterior cerebral artery were significantly vasospasm(P < 0.05).5.The FA value of cerebral peduncle in SAH group was decreased(P < 0.05),but there was no significant change in the pyramidal tract.6.m NSS score of medium TBI rats with SAH was increased(P < 0.05),and recovered at about 10 days.7.Significant cerebral vasospasm was observed in the saline and deferoxamine treatment groups on the first 3-7 days after operation(P < 0.05 or P < 0.01);nimodipine treatment group did not appear obvious cerebral vasospasm.8.The MWM performance of the saline and nimodipine treatment groups were significantly worse than that of the deferoxamine treatment group(P < 0.05),and the cerebral volume and the reduction of the cortical and hippocampal neurons in the saline and nimodipine treatment groups were more significant than that in the deferoxamine treatment group(P < 0.05).Conclusion1.Repeated single asymptomatic mild TBI can lead to cognitive impairment.2.The cognitive function is more likely to be damaged than the sensory motor function in repeated mild TBI.3.The atrophy of the cerebral cortex and hippocampus of the rats with cognitive impairment after repeated mild TBI was obvious.4.The acute injury of white matter and gray matter recovered quickly after mild impact.5.The modified rat model of double blood SAH was minimally invasive and has high success rate and low death rate.6.The corticospinal tract in SAH rats was injured in the cerebral peduncle but not in the medulla oblongata.7.Short term use of nimodipine can significantly improve the cerebral artery spasm of TBI rats with SAH,but can not improve the late changes in brain structure,MWM performance and neuronal death.8.The deferoxamine can not reduce the vascular spasm but effectively improve the structure of the brain changes,MWM performance and neuronal death. |
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