Study On The Effect And Mechanism Of Sensory Integration Training On Improving Cognitive Impairment In Young Rats With Traumatic Brain Injury

Background and Purpose:With the development of modern industry,power machinery and high-speed transportation,the incidence rate of Traumatic brain injury(TBI)is increasing.Globally,TBI is one of the main causes of death and disability.Cognitive impairment is one of the most common and lasting neurological complications of secondary injury after TBI,and cognitive impairment may be the main cause of long-term dysfunction,bringing serious harm to patients’daily life,learning,work and social activities,not only seriously affecting the quality of life of patients,but also adversely affecting rehabilitation treatment,leading to poor prognosis of TBI patients.The treatment options for TBI are still limited,so how to improve TBI and cognitive impairment after TBI is a difficult problem to be solved urgently.Sensory integration was proposed by Dr.Ayers,an American clinical psychologist.It mainly includes vestibular system,tactile system and proprioception system.Only when the three systems operate well and interact with the brain,can our language development,cognitive function,body coordination,social adaptability and other aspects develop well.Sensory integration training can improve sensory integration disorder,enhance neural plasticity and brain integration function through conscious structured training,thus improving body dysfunction.Sensory integration training has a positive impact on children with cognitive impairment,and its therapeutic purpose is achieved by correcting and improving children’s behavior,cognition and social skills.However,the application effect and mechanism of sensory integration training in cognitive impairment after TBI are still unclear,which needs further study.Method:In this study,the TBI young rat model was established by the improved Feeney method,and the TBI young rats were continuously intervened by sensory integration training for one week.The improvement effect and molecular mechanism of sensory integration training on cognitive impairment of young rats with brain injury were explored by using behavioral,Golgi staining,Brd U labeling,immunofluorescence staining,Western blot,RT-q PCR,HE staining,and the intervention of localized injection of ACKR2 adenovirus over-expression vector into the lateral ventricle.Result:(1)Morris water maze experiment found that sensory integration training could improve the memory impairment of TBI young rats;Through the open-field experiment,pole climbing experiment and rod rotation experiment,it was found that sensory integration training could improve the cognitive impairment of TBI young rats.In order to study the causes of behavioral changes in young rats,the changes in the proportion of different dendritic spines in the hippocampus and the expression of proteins related to learning and memory were analyzed.The results showed that sensory integration training increased the density of dendritic spines,increased the proportion of Mushroom-like small spines,decreased the proportion of Stubby-like small spines,and increased the expression level of synapse-related proteins PSD95and SPN,thus improving the cognitive impairment caused by TBI.(2)The m RNA levels of IL-1β,IL-6 and TNF-αin hippocampal tissue of young rats were up-regulated by TBI,and the m RNA levels of IL-1β,IL-6 and TNF-αwere decreased by sensory integration training.Immunofluorescence staining showed that sensory integration training inhibited the activation of microglia by reducing the density of Iba1~+cells in the dentate gyrus,subgranulosa cell and molecular layer.Sensory integration training could significantly inhibit the increase of TLR4,p-p38/p38 and p-NF-κB/NF-κB protein levels in the hippocampus of TBI young rats.(3)The number of DCX~+cells in hippocampal Subgranular zone(SGZ)of rats was reduced by TBI,and the length of the DCX~+cells was shortened by sensory integration training,but the number of DCX~+cells was increased and the length of the process was extended by TBI.Compared with the TBI group,sensory integration training significantly increased the expression levels of nerve growth factors NGF and BDNF proteins in the hippocampus,increased the number of Brd U~+and Brd U~+Neu N~+cells,and promoted the differentiation of new hippocampal cells into neurons.In addition,the percentage of Brd U~+GFAP~+co-labeled cells was significantly decreased,and the differentiation of neural progenitor cells into astrocytes was inhibited.(4)Overexpression of ACKR2 alleviated cognitive impairment in TBI young rats by shortening the escape latency and increasing the number of platform crossing.Young rats injected with adenovirus overexpression vector ACKR2 had less edema in brain tissue,neuron nuclei were clearly visible,and neuron integrity was significantly improved.Overexpression of ACKR2 significantly decreased the levels of CCL2,IL-1β,TNF-αand the expressions of Tau and NG2,and up-regulated the expression of ACKR2.Conclusion:(1)Sensory integration training alleviates cognitive impairment after TBI by increasing synaptic plasticity.(2)Sensory integration training can improve cognitive impairment by inhibiting the activation of TLR4/p38 MAPK and NF-κB inflammatory pathway,thereby inhibiting the activation of microglia cells and the release of inflammatory factors.(3)Sensory integration training promotes adult hippocampal neurogenesis by promoting neural stem cell proliferation and neuronal differentiation,and reducing neural progenitor cell differentiation into astrocytes,thus inhibiting the pathological process of cognitive impairment.(4)Sensory integration training plays a role in improving cognitive impairment after TBI by regulating ACKR2 expression in the brain.