| Objective:? To investigate the change of serum mannose-binding lectin concentrations in patients with aneurysmal subarachnoid hemorrhage and its relation to the severity and functional outcome of subarachnoid hemorrhage,analyze the value of serum mannose-binding lectin for severity assessment and prognostic prediction after aneurysmal subarachnoid hemorrhage and further discuss the clinical significance of clinical determination of serum mannose-binding lection.?To observe the influence of intraventricularly-injected anti-mannose-binding lectin antibody on neurological function,cerebral water content,permeability of blood-brain barrier,neuronal cellular apoptosis,as well as protein expression levels of C3,mannose-binding lectin-C,Toll-like receptor 4,p65 and phosphoryalted p65,ascertain the effect of mannose-binding lectin in early brain injury after subarachnoid hemorrhage in rats and signalling-mediating mechanisms of mannose-binding lectin's involvement in pathophysiological process of early brain injury following subarachnoid hemorrhage,and further discuss the clinical value of mannose-binding lectin acting as a new target for drug use.Methods:? We selected a total of 62 patients with aneurysmal subarachnoid hemorrhage(case group)and 62 healthy individuals(control group),used enzyme-linked immunosorbent assay to measure serum mannose-binding lectin concentrations,performed Mann-Whitney U test to compare serum mannose-binding concentrations between case group and control group,utilized Spearman correlation analysis and Kruskal-Wallis-H test to determine the relationship between serum mannose-binding lectin concentrations and world federation of neurological society scale?HUNT-HESS score in addition to modified Fisher score;6 months of follow-up was done for case group and an unfavorable outcome was defined as Glasgow outcome scale score of 1 to 3.Mann-Whitney U test was carried out for the comparison of serum mannose-binding lectin concentrations between patients with unfavorable outcome and those with favorable outcome.Receiver operating characteristic curve was configure to discern the predictive value of serum mannose-binding lectin for 6-month unfavorable prognosis.? SD rats were randomly assigned into sham-operation group,subarachnoid hemorrhage group and treatment group,with 6 rats in each group.The subarachnoid hemorrhage model was established via injection of autologous blood into the rat's cistema magna.The rats in treatment group were given an intraventricular administration of dimethyl sulfoxide solution containing anti-mannose-binding lectin antibody after the formation of rat model,an equal volume of dimethyl sulfoxide solution was injected into ventricular space following the establishment of rat model in subarachnoid hemorrhage group and a same volume of dimethyl sulfoxide was injected intraventricularly after an injection of the same amount of normal saline into the rat's cisterna magna in sham-operation group.After rats were killed,hemorrhagic distribution was observed grossly in the rat brain surface,pathological change of damaged brain tissues was investigated using hematoxylin-eosin staining,expression of mannose-binding lectin in brain tissues was detected using immunohistochemical staining and western blot respectively,terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling was done to measure neuronal cellular apoptosis,western blot was performed to determine protein expressions of C3,Toll-like receptor 4,p65 and phosphoryalted p65,dry and wet method was carried out to investigate cerebral water content,Evans Blue was utilized to analyze blood-brain barrier permeability and neurological function was assessed according to the Kaoutzanis' report.Among three groups,namely,sham-operation group,subarachnoid hemorrhage group and treatment group,each parameter was compared using one-way variance analysis and the least significant difference method was adopted in the comparison between two groups.Results:?Patients with aneurysmal subarachnoid hemorrhage had pronouncedly higher serum mannose-binding lectin concentrations than healthy controls(P<0.001),serum mannose-binding lectin concentrations were profoundly higher in patients with unfavorable outcome than in those with favorable outcome(P<0.001),serum mannose-binding lectin concentrations were positively correlated with world federation of neurological society scale score,HUNT-HESS score and modified Fisher score(all P<0.001)as well as serum mannose-binding lectin exihited a significant predictive value for 6-month unfavorable outcome(P<0.001).?No obvious bleeding was present in the brain surface of rats in sham-operation group,whereas there was remarkable bleeding in the brain surface of rats both in subarachnoid hemorrhage group and treatment group;brain tissues were not obviously damaged of rats in sham-operation group,were remarkably injured in rats of subarachnoid hemorrhage group,while damage in brain tissues was significantly alleviated in rats of treatment group;as compared with sham-operation group,neuronal cellular apoptosis and protein expressions of mannose-binding lectin-C,C3,Toll like receptor 4,p65 and phosphoryalted p65 were subtantially raised in rat brain tissues of subarachnoid hemorrhage group(all P<0.05),while neuronal cellular apoptosis and protein expressions of mannose-binding lectin-C,C,Toll like receptor 4,p65 and phosphoryalted p65 were obviously lower in rat brain tissues of treatment group than subarachnoid hemorrhage group(all P<0.05);cerebral water content and blood-brain barrier permeability were markedly higher in subarachnoid hemorrhage group than in sham-operation group(all P<0.05),whereas cerebral water content and blood-brain barrier permeability were pronouncedly lowered in treatment group,as opposed to subarachnoid hemorrhage group(all P<0.05);rats in subarachnoid hemorrahge group were more prone to suffer from neurological deterioration than those in sham-operation group(all P<0.05),but rats in treatment group were more likely to experience recovery of neurological function than those in subarachnoid hemorrhage group(all P<0.05).Conclusions:? Serum mannose-binding lectin concentrations have an intimate relation to the severity and prognosis after aneurysmal subarachnoid hemorrhage,hinting that serum mannose-binding lectin might be a potential prognostic biomarker for aneurysmal subarachnoid hemorrhage.? Expression of mannose-binding lectin-C rises significantly in brain tissues of rats with subarachnoid hemorrhage as well as anti-mannose-binding lectin-C antibody is able to substantially inhibit cortical neuronal cellular apoptosis of rats,significantly abated brain edema,pronouncedly improved blood-brain barrier,and markedly lessen neurological dysfunction,simultaneously accompanied with the profound down-regulation of protein expressions of C3,Toll like receptor 4,p65 and phosphoryalted p65.Thus,clinical determination of serum mannose-binding lectin concentrations can aid in the assessment of severity and prognosis of subarachnoid hemorrhage,subsequently guiding clinical risk stratification and further resulting in the improvement of curative ratio;mannose-binding lectin might be implicated in pathophysiological process underlying early brain injury induced by subarachnoid hemorrhage and inhibition of mannose-binding lectin expression possibly paves a way for the treatment of brain injury caused by subarachnoid hemorrhage. |
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