Effects Of Controlled Decompression On The Expression Of UCH-L1,GFAP,Oxidative Damage And Neuroinflammation In Rabbits With Acute Intracranial Hypertension

ObjectiveThe benefits of controlled decompression（CDC）for patients with acute intracranial hypertension especially in terms of alleviating the complications caused by rapid decompression（RDC）have been confirmed by clinical studies.This study aims to evaluate the therapeutic potency of CDC with Ubiquitin C-terminal hydrolase-L1（UCH-L1）and Glial fibrillary acidic protein（GFAP）by investigating the potential molecular mechanism in the acute intracranial hypertension（AICH）rabbit model.MethodsMale New Zealand white rabbits were randomly subdivided into sham-operated（SH）group,CDC group and RDC group.Blood plasm samples and brain tissue were collected 2 days before operation（baseline）and at 3,6,24 and 72 hours after operation to measure the levels of UCH-L1,GFAP,oxidative stress indicators and inflammatory cytokines by performing ELISA or Western blot.The neurological score of the rabbits and brain water content were graded 24 h after surgery.q PCR,immunofluorescence and FJ-C staining were used to evaluate UCH-L1 and GFAP expression and neuronal degeneration in different groups,respectively.ResultsCDC improved neurological function（3.25±0.75vs4.17±0.83,P<0.05）,lowered brain water content（78.23±1.29vs80.41±1.23,P<0.05）,ameliorated neuronal degeneration（116.5±7.89vs149.7±7.63,P<0.01）,suggesting that CDC may have a better neuroprotective effect.The oxidative damage markers MDA and 8-iso-PGF2α in plasma and cortex at different time in CDC group were lower than those in RDC group（P < 0.05）,while the antioxidant enzyme SOD was higher than that in RDC group（P < 0.05）.The levels of inflammatory molecules（TNF-α,IL-1β,IL-6,IL-8）in the CDC group were lower than those in the RDC group（P < 0.05）,suggesting that the neuroprotective effect of CDC may be achieved by reducing oxidative damage and neuroinflammation.Immunofluorescence confirmed that the expression of UCH-L1 and GFAP in CDC group was lower than that in RDC group（UCH-L1:26.23±2.3vs38±2.7,P<0.01;GFAP:37.75±2.6vs43.9±2.9,P<0.01）.ELISA showed Plasm UCH-L1 level was significantly lower in the CDC group at 3h postoperatively than that in the RDC group（2.8±0.49vs4.4±0.57,P < 0.01）.CDC reduced plasma GFAP levels to various degrees at 3h,6h and 24 h postoperatively compared with RDC（446.6±73.4vs751.9±121.3,P < 0.01;651.1±81.5vs1047.6±111.9,P < 0.01;312.7±51.2vs425.6±92.4,P < 0.05）.Western blot showed that UCH-L1 expression was lower in the CDC group than in the RDC group at 3h postoperatively（0.64±0.07vs1.07±0.1,P < 0.01）,The level of GFAP in the CDC group was lower than that in the RDC group at 6h postoperatively（0.64±0.05vs1.06±0.09,P < 0.01）.ConclusionsOur data collectively demonstrate that CDC could attenuate oxidative damage and inflammatory responses,down-regulate UCH-L1 and GFAP levels,and contribute to an improved neuroprotective effect compared with RDC.