Effects Of Decompressive Craniectomy Combined With Mild Hypothermia On The Expression Of TRPM2、Caspase-9 In Rats With Severe Traumatic Brain Injury

Objective: To investigate following topics via severe craniocerebral injury model established by improved Feeney’s free falling body injury device:1.To study the effect of mild hypothcrmia on rat TRPM2、Caspase-9 expression level after severe craniocerebral injury;To study the effect of decompressive craniectomy on rat TRPM2、Caspase-9 expression level after severe craniocerebral injury;2.To study the effect of mild hypothcrmia combining with decompressive craniectomy on rat TRPM2 、Caspase-9 expression level after severe craniocerebral injury;3.To compare the curative effects between two different methods via rat TRPM2 、Caspase-9 expression after severe craniocerebral injury;4.To provide theoretical evidence to TBI treatment regarding TRPM2 pathway targeting.Methods: A total of 192 SPF grade adult male rats with body weight ranging from 280 g to 240 g were selected in this study.The rats were randomly and evenly divided into 4 groups,namely severe craniocerebral injury group(STBI group with only drilling damage),severe craniocerebral injury with mild hypothcrmia group(STBI+MHT group),in severe craniocerebral injury with decompressive craniectomy group(STBI+DC group),and severe craniocerebral injury combining with mild hypothcrmia and decompressive craniectomy group(STBI+MHT+DC group).48 rats in each group were further equally categorized into 6 subgroups according to different timing after damage,which is 6h,12 h,24h,48 h,72h and 168 h.The rats were beheaded at above-mentioned time,and the damaged brain tissues were tested in water content(dry-wet weighting method)and TRPM2、Caspase-9 expression(immunohistochemical method).Results: Dry-wet weighting method:For STBI group,water content from dry-wet weighting method indicated starting to increase at 6h,gradually increasing at 12 h,peaking at 24 h,slightly decreasing at 48 h,obviously decreasing at 72 h and significantly deceasing at 168 h after Severe traumatic brain injury.For STBI+MHT group,water contents were gradually increasing at 6h,12 h,peaking at 24 h,gradually increasing at 48 h,72h,and oedema was still observed at 168 h after Severe traumatic brain injury.The significant difference were noticed at each time point between STBI and STBI+MHT(p<0.05);For STBI+DC group,water contents were gradually increasing at 6h,12 h,peaking at 24 h,gradually decreasing at 48 h,72h,and oedema was still noticeable at 168 h after Severe traumatic brain injury.Comparing to the results of STBI group,differences were significant at each time point(p<0.05),Comparing to the results of STBI+MHT group,differences were significant at each time point(p<0.05);For STBI+MHT+DC group,Very significant differences were gained between STBI+MHT+DC and STBI group(p<0.05),and significant differences were obtained between STBI+MHT+DC and STBI+DC group(p<0.05),and significant differences were obtained between STBI+MHT+DC and STBI+MHT group(p<0.05);Very significant differences were observed at most timings(p<0.05).Immunohistochemical results:The TRPM2 positive cells expression changed over time,and presented a high-low pattern at selected timings,which was increasing at 6h,peaking at 24 h,and bottoming at 168 h.Significant difference was noticed between STBI+MHT and STBI group in all results(p<0.05),as well as between STBI+DC and STBI group(p<0.05);All results in STBI+DC and STBI+MHT group were significantly different(p<0.05);Very significant differences were gained between STBI+MHT+DC and STBI group(p<0.05),and significant differences were obtained between STBI+MHT+DC and STBI+DC group(p<0.05),and significant differences were obtained between STBI+MHT+DC and STBI+MHT group(p<0.05);Very significant differences were observed at most timings(p <0.05).The Caspase-9 positive cells expression changed over time,and presented a high-low pattern at selected timings,which was increasing at 6h,peaking at 24 h,and bottoming at 168 h.Significant difference was noticed between STBI+MHT and STBI group in all results(p<0.05),as well as between STBI+DC and STBI group(p<0.05);All results in STBI+DC and STBI+MHT group were significantly different(p<0.05);Very significant differences were gained between STBI+MHT+DC and STBI group(p<0.05),and significant differences were obtained between STBI+MHT+DC and STBI+DC group(p<0.05),and significant differences were obtained between STBI+MHT+DC and STBI+MHT group(p<0.05);Very significant differences were observed at most timings(p<0.05).Conclusion: Rat severe craniocerebral injury model was successfully established by improved Feeney’s free falling body injury device,which is outstanding in simplicity,controllability and repeatability;Craniocerebral injury and oxidative stress led to TRPM2 overexpression,Caspase-9 expression levels increased,resulting in increased cell apoptosis and aggravated brain damage;Decompressive craniectomy and mild hypothcrmia had respective curative effects on craniocerebral injuries;however,their synergistic effect in combined treatment was superior to single therapy.