Interleukin-1β Induces The Upregulation Of Cyclooxygenase-2and Microsomal Prostaglandin E2Synthase-1in The Middle Cerebral Artery From Patients With Moyamoya Disease

Part1:Upregulation of COX-2and mPGES-1in the middle cerebral artery from patients with moyamoya diseaseObjective Some inflammatory proteins, such as cyclooxygenase (COX)-2and microsomal prostaglandin E2synthase-1(mPGES-1) are believed to be implicated in the development of moyamoya disease (MMD). However, the expression of COX-2and mPGES-1in intracranial vessels of MMD patients is still unknown. The purpose of this part to explore the expression of COX-2and mPGES-1in the middle cerebral artery from patients with moyamoya disease.Methods The clinical data of MMD patients who treated by superficial temporal artery-middle cerebral artery bypass and temprolis muscle attachment (STA-MCA bypass+EMS) and other patients who undergone extra-intracranial high flow bypass (EC-IC) in our hospital during June2013and December2014were retrospectively analyzed. The plasma samples of all patients were collected at admission and tiny pieces of MCA and STA were surgically harvested from all the patients. The thickness of the intima of the MCA was measured in hematoxylin and eosin-stained (HE) sections. The expression of COX-2and mPGES-1in the vessels of MCA and STA were detected by immunohistochemical methods. The plasma concentration of COX-2and prostaglandin (PG) E2were analyzed by an enzyme linked immunosorbent assay (ELISA).Results Due to the extreme difficulty to obtain the samples of intracranial arteries, only18cases of MMD and5cases of control patients were include in the present study. The HE staining indicated that MCA specimens from MMD patients had a thicker intima than those from the control group (t=9.252, P=0.000). While positive expression of COX-2was observed in MCA of most MMD patients (15/18,83.3%), all MCA of MMD patients were stained positively for mPGES-1(18/18,100%). Based on the grouping of different clinical indicators, all comparisons of COX-2or mPGES-1expression in the "gender" group, "radiographic grade" group, and "lesion location" group were no significant differences (Pall>0.05). However, staining of both COX-2and mPGES-1were more abundant in the MCA of hemorrhagic patients than those in their ischemic counterparts (P=0.001and0.029, respectively). There was a strong positive correlation between the expression of COX-2and mPGES-1(r=0.647, P=0.004). Positive COX-2and mPGES-1expression were detected neither in the MCA samples from the controls nor in all STA specimens. The plasma concentrations of both COX-2and PGE2were not different between the MMD patients and the control group (Pboth>0.05).Conclusion Our results suggest that both COX-2and mPGES-1are up-regulated in the MCA of MMD patients and are highly expressed in hemorrhagic patients. We speculate that COX-2/mPGES-1may be involved in the pathogenesis of MMD and even contribute to the hemorrhagic stroke of adult MMD patients. Objective To explore the expression of IL-1β and its receptor (IL-1R I) in MMD patients and analyze their molecular mechanisms in the development of MMD.Methods The expression of IL-1R I in the vessels of MCA and STA were detected by immunohistochemical methods. The plasma concentration of IL-1β were investigated by an enzyme linked immunosorbent assay (ELISA). Based on the grouping of different clinical indicators, the expression of IL-1β and IL-1R I in the "gender" group,"radiographic grade" group,"lesion location" group, and "clinical presentation" group were respectively compared. The correlation between the expression of IL-1R I and the expression of COX-2or mPGES-1in the MCA were both analyzed. At present, only one study of MMD was reported using intracranial vessels. Combined with the result of the study, we tried to analyze the possible roles of the mediaters and proteins mentioned above in the the development of MMD.Results The vessel samples of all patients in our study were stained positively for IL-1R I. However, staining of IL-1R I was more abundant in the MCA than that in the STA of MMD patients (t=7.733,P=0.000) and that in the MCA of control patients (t=3.248,P=0.004). The expression levels of IL-1R I in the MCA of hemorrhagic patients were much higher than those in their ischemic counterparts (t=2.669,P=0.017). There were strong positive correlations between the expression of IL-1R I and COX-2(r=0.536,P=0.022) or mPGES-1(r=0.676,P=0.002) in the MCA of MMD patients. Positive expression of IL-1β in the plasma were observed in all patients in our study. However, MMD patients exhibited significantly higher plasma concentrations of IL-1β compared with the controls (t=2.456,P=0.023). Unexpectedly, there was no obvious different of the plasma concentrations between hemorrhagic MMD patients and their ischemic counterparts (t=1.352, P=0.195).Conclusion IL-1β may play a key role in the pathogenesis of MMD through activating COX-2and mPGES-1in the wall of MCA. Pharmacological interference with IL-1β signaling and downregulating COX-2/mPGES-1could have therapeutic value in the prevention of the development of MMD and the occurrence of hemorrhagic stroke. Part3:Evaluation of the curative effect of combined revascularization for adult patients with moyamoya disObjective To investigate the clinical significance and curative effect of combined revascularization (STA-MCA bypass+EMS) for the18adult cases of moyamoya disease.Methods Clinical data of the patients were recorded in detail. All patients were followed up in the outpatient clinic for three months. There were12cases in the patients had organic changes. The neurological conditions of them were evaluated by the national institutes of health stroke scales (NIHSS) before surgery and at three months after the operation. The overall efficiency of STA-MCA bypass+EMS for the18MMD cases was investigated Based on the grouping of different curative effects, the expression of COX-2, mPGES-1and IL-1R I in the "excellent" group,"effective" group, and "invalid" group were respectively compared. The efficiencies of STA-MCA bypass+EMS for hemorrhagic MMD and ischemic MMD patients were compared.Results The NIHSS scores of the12MMD cases with organic changes at three months after the operation were much lower than their preoperative scores (t=6.416, P=0.000). The total effective rate of STA-MCA bypass+EMS for the18MMD patients was up to88.9%. Further analysis found that there were no obvious correlations between the expression levels of COX-2, mPGES-1or IL-1R I and the short-term effects of STA-MCA bypass+EMS for these MMD patients. There was no different between the efficiency of STA-MCA bypass+EMS for hemorrhagic MMD patients and that for ischemic MMD patients (P>0.05).Conclusion STA-MCA bypass+EMS can significantly improve the prognosis of patients with MMD. It is not only recommended for ischemic MMD patients but also for hemorrhagic cases.