Effects And Mechanisms Of Lats1/p-YAP1 Pathway In Rat's Secondary Traumatic Brain Injury

ObjectiveTo investigate the roles of Lats1/p-YAP1 pathway in TBI-induced neuronal apoptosis and neurological deficits in rats.Methods1.we collected the rat's brains at 6 hrs,12 hrs,24 hrs,48 hrs and 72 hrs after TBI,then we examined the protein levels and the expression and location of Lats1 and p-Lats1 in the cortex tissue of each group by western blot and immunofluorescence detect the time course of the protein levels of Lats1,p-Lats1 and p-YAP1 and the location of these molecules in cerebral cortex tissue,meanwhile detect the neuronal apoptosis and BBB damage following TBI.Next,we examined the protein levels and the expression and location of Lats1 and p-Lats1 in the cortex tissue of each group by western blot and immunofluorescence?2.The rats were divided into three groups:sham group,control si RNA group and Lats1 si RNA group(TBI group),according to the randomized grouping method.First,we performed intraventricular injection of si RNA vehicle and Lats1 si RNA.At 24 hrs after intracerebroventricular injection,the rats in control si RNA group(TBI group)and Lats1 si RNA group were performed brain trauma.Meanwhile,the sham group was treated with a sham wound.At 24 hrs after TBI and sham trauma,all the rats were sacrificed and the cortical tissues around the damaged area and the same location tissues of sham group were used for the following each experimental analysis.At last,we analyze the role and the mechanism of Lats1 in the pathogenesis of TBI.Results:We found that Lats1 and YAP1 were expressed in cerebral cortex neurons of Sprague-Dawley rats,and the phosphorylation levels of Lats1 and YAP1 in injured regions were significantly increased after TBI.Furthermore,inhibition of Lats1,not only the level of p-YAP1 decreased,but also attenuated neuronal apoptosis and neurological impairment.ConclusionsIn our work,we illustrated the role of Lats1/YAP1 in pathogenesis of a rat model of TBI.The main novelties of our work are as follows:(1)we found that Lats1 participates in the pathogenesis of TBI in rat;(2)we demonstrated that Lats1 was involved in the regulation of TBI by regulating the phosphorylation of downstream YAP1;(3)the inhibition of Lats1/YAP1 pathway mitigated neuronal apoptosis and neurological deficits.