The Role Of Activin Receptor-interacting Protein 2 In Traumatic Brain Injury

Objective:Traumatic brain injury(TBI)is an important global public health problem.Every year,at least 10 million TBI patients are severe enough to cause death or hospitalization.Even mild TBI patients can cause long-term disability.Whether it is individuals or society,TBI has caused a huge economic burden.However,despite a gradual increase in the knowledge of the mechanisms of TBI pathophysiology and various promising findings,there are still no clear and effective treatments and measures.Activins are members of the TGF-? family and act as multifunctional regulatory proteins in many tissues and organs.In the brain,Activin A can act as a neurotrophic factor during development.Studies have shown that Activin A expression is strongly upregulated after acute brain injury in adults,which has shown to provide effective neuroprotection in various injury models.The biological effects of Activin A are achieved through the mediation of activin receptor signaling pathways.Recent studies have found that in their signaling pathways there is a new set of specific signaling proteins known as ARIPs(activin receptor interacting proteins)family that mediate activin signalling.Among them,ARIP2 may be a key signaling molecule of Activin A in nerve cells.In this study,a mouse model of closed brain injury was induced by free-fall impaction.The behavioral changes were recorded.The expression of ARIP2 in hippocampus and cortex of brain tissue of each group was detected and analyzed its possible relationship with TBI,further explore the mechanism of Activin A to exert its biological activity,,so as to be able to find possible targets for guiding clinical drug treatment of TBI.Methods:A mouse model of closed brain injury was prepared by free-fall impaction.The free-fall brain injury model was used to hit unilaterally the forebrain area of the mouse.The control group only cut the opening of the brain without any treatment.The model was successfully randomized.Divided into 1d,3d,and 5d groups after brain injury.To explore the role of ARIP2 in traumatic brain injury,the dynamic changes of ARIP2 and Activin A in hippocampal and cortical and were observed by HE staining,immunohistochemistry,Western Blot and RT-PCR.Results:1.RT-PCR results showed that ARIP2 and Activin A were significantly increased in the experimental group compared to the control group on the 1st day,and ARIP2 continued to increase on the 3rd day,while Activin A was significantly reduced compared to 1d on the 3rd day.2.Immunohistochemical staining showed that a large number of ARIP2-positive cells were seen in the cortex and hippocampus(significantly in CA1,CA3,and DG regions)of the experimental group.Compared with the control group,the expression of ARIP2 protein increased at 1d,reached a high level for 3d,and decreased at 5d.3.Western Blot results showed that ARIP2 in the cortex and hippocampus of experimental group mice began to increase at 1d after brain injury and reached a peak at 3d.Compared with the control group,Activin A increased at 1d after brain injury,and then decreased continuously at 3d.Conclusions:1.The expression of ARIP2 in hippocampus(CA1,CA3,DG)is obvious,ARIP2 may be involved in the process of traumatic brain injury caused by free fall impact.2.Activin A increased first and then decreased in the cortex and hippocampus,with the most significant increase at 1d.3.ARIP2 may participate in the role of Activin A in the TBI process.