The Role Of Activin Receptor-interacting Protein 1 And Activin A In Traumatic Brain Injury

Objective:Traumatic brain injury(TBI)is a physical injury that temporarily or permanently damages the functions of brain tissue and has become a growing public health epidemic.The etiology,severity,pathogenesis and clinical outcomes are different.With the increasing public awareness of TBI and its consequences,people are increasingly required to understand the underlying mechanisms and to carry out relevant therapeutic interventions.Activin A is a multifunctional growth and differentiation factor of the transforming growth factor-?(TGF-?)family,and more and more evidence shows that it has neuroprotective properties after nerve injury.In recent years,however,an activin-specific signal transduction protein-activin receptor interacting protein 1(ARIP1)was found in studies of cell signaling pathways related to activin,ARIP1 may be the key signaling molecule that determines Activin A's role in neural cells.The subject of this experiment was to establish a mouse model of free-fall brain injury,observe and record its behavioral changes,and detect the expression of ARIP1 mRNA and protein in hippocampus and cortex of each group of mouse brains and their relationship with Activin A,then to explore the relationship between ARIP1,Activin A and traumatic brain injury,and to provide new therapeutic ideas and research targets for innovative treatment of TBI.Methods:Preparation of a mouse model of free-fall impacted brain injury.In the TBI group,a ZH-ZYQ type free-fall impacted brain injury model was used to hit unilaterally the forebrain area of the mouse.The Sham group only cut the opening of the head without any treatment and then randomly divided into groups 1d,3d,5d,and 7d after traumatic brain injury.The dynamic expression of ARIP1 and Activin A in the cortex and hippocampus of the mouse brain tissue was observed by RT-PCR,hematoxylin-eosin(HE)staining,immunohistochemical DAB staining and Western Blot,so as to explore the possible mechanism of ARIP1 in the process of traumatic brain injury and its relationship with Activin A.Results:1.RT-PCR results showed that ARIP1 and Activin A in each model group increased significantly after 1d,while Activin A protein significantly decreased at 3d,ARIP1 continued to increase at 3d after TBI.2.The results of immunohistochemical DAB staining showed that ARIP1 positive cells were seen in the cortex and hippocampus of Sham and injured brain tissue in each group,but there were significant differences(especially hippocampal CA1,CA3,and DG regions).Compared with Sham group,the expression of ARIP1 protein was significantly increased on the 1st day,increased continuously with time,peaked on the 3rd day,and gradually weakened on the 5-7th day.3.Western Blot results showed that ARIP1 in cortex and hippocampus of mice in TBI group increased significantly at 1d after brain injury and peaked at 3d,which was consistent with immunohistochemical results.Compared with Sham group,Activin A was significantly increased 1d after brain injury,and decreased continuously at 3d.Conclusions:1.Changes of ARIP1 in the cortex and hippocampus(CA1,CA3,DG)is more obvious,ARIP1 may be involved in the process of traumatic brain injury caused by free fall impact.2.ARIP1 may be involved in the role of Activin A in traumatic brain injury and may inhibit Activin A in the early stages of injury.