| Background:Subarachnoid hemorrhage (SAH) is a devastating neurological condition that results in high mortality and disability. Cerebral vasospasm (CVS) is regarded as a key factor for delayed cerebral ischemia (DCI), which is considered as the most serious complication of SAH. Commonly, oxidative stress and inflammation were believed included in mechanism of CVS. Based on a series of research, hydrogen (H2), which usually applied in prevention of treatment of decompression sickness, indicated the benefit effect on ischemia-reperfusion injury, cerebral hypoxia-ischemia and inflammation. The effect may be explained with anti-oxidative stress and anti-inflammation. In view of the bad safety and storage of hydrogen gas, hydrogen saturated saline (HS) was applied in many researches. More works will still be needed to find the exact mechanism about neuroprotective effect of H2and HS, and the same to the best way to application in clinical therapy. Objective:Considering that oxidative stress and inflammation play an important role in the pathogenesis of CVS after SAH, we would like to determine the possible anti-oxidative and anti-inflammatory mechanism of HS on SAH-induced cerebral vascular injury using neurological, biochemical, and histopathological approaches based on rats SAH model. Moreover, we also would like to find a new route of treatment to CVS after SAH.Method:With establishment of rat SAH model, the rats were randomly divided into three groups:1)sham-operated plus physiological saline vehicle treatment (n=20),2) SAH plus physiological saline vehicle treatment (n=20), and3) SAH plus HS treatment (n5=20). Either HS (5ml/kg intraperitoneally) or an equal volume of saline was administered immediately after the surgery and repeated24h later. After48h of surgery, the rats were killed and cerebral basilar artery (BA) were taken for experimental samples which were maintain by different ways for histopathological and biochemical analyses. MDA, SOD and GPx were tested for check level of oxidative stress, while NF-κB, IL-1β, IL-6, TNF-a and ICAM-1were chosen for inflammation level test. All above were contained in research on protective effect of HS to SAH-induced CVS in rats.Statistical analysis was coped with SPSS software19.0(SPSS, Chicago, IL). Data are presented as mean±SD or median for continuous values or median (range) for discontinuous values. Comparison among groups was made by ANOVA for continuous variables or by Kruskal-Wallis analysis for discontinuous variables. The difference was regarded as statistically significant at P<0.05. Results:Compared with the vehicle-treated group, the HS treatment resulted in a significantly greater reduction of neurological deficits48h after SAH (median score4[3-5] vs.9[7-11], P<0.05).In histopahological study, HS treatment significantly increased the luminal inner perimeter and reduced the wall thickness of the BA compared with the vehicle control(perimeter:829.37±18.61vs658.45±15.06μm, P<0.01; wall thickness:16.89±0.84vs25.1±0.94μm, P<0.01). In addition, treatment with HS significantly decreased the elevated MDA levels and increased the reduced antioxidant enzyme activities (MDA:0.93±0.04vs1.56±0.06nmol/mg, P<0.01; SOD:37.81±2.58vs25.17±2.12U/mg, P＜0.01; GPx:103.43±3.82vs74.57±3.21nmol/min/mg, P<0.01). In the SAH+HS group, arterial NF-κB binding activity was significantly down-regulated after HS injection (8.77±0.68vs17.43±0.77ADU, P<0.01). HS treatment lowered the SAH-induced elevation of vascular IL-1β, IL-6, TNF-a, and ICAM-1concentrations (IL-1β:31.54±3.25vs65.6±2.48pg/mg, P<0.01; IL-6:3.95±0.18vs7.03±0.20pg/mg, P<0.01; TNF-α:1.20±0.17vs2.16±0.20pg/mg, P<0.01; ICAM-1:3.08±0.21vs6.11±0.35pg/mg, P<0.01).Conclusion:The present study is an in vivo experiment to demonstrate beneficial and preventive effects of H2on SAH-induced CVS. This protective effect mainly is due to its ability to limit and alleviate injuries caused by oxidative stress and vascular inflammation. |
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