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Objective To investigate the effect of inhibition of endoplasmic reticulum stress (ERS) in ischemic preconditioning-induced cerebral ischemia tolerance.Methods A total of 120 adult male SpragueDawley rats were randomly allocated into three groups:sham operation,global cerebral ischemic and ischemic preconditioning groups (ischemic preconditioning for 3 minutes,and global cerebral ischemia for 15 minutes after 2 days).Three time points (day 1,day 3 and day 7) were set.Sugawara method was used to observe the changes of neurological behavior in rats.TUNEL staining was used to observe the conditions of cortical neuronal apoptosis.Immunofluorescence staining and Western blot analysis were used to detect the expression levels of ERS-related protein CHOP,GRP78,and caspase-12.Results The neurological behavior score showed that the sham operation group did not have neurological deficits.Both the global cerebral ischemic group and the ischemic preconditioning group had obvious neurological deficits,and they improved gradually with the passage of time,but after modeling,the neurological scores at each time point in the global cerebral ischemic were significantly lower than those in the ischemic preconditioning group:at day 1∶11.00 ±0.63 vs.14.33 ±0.33 (t =21.74,P＝0.001); at day 3∶ 12.17±0.31vs.15.17±0.48 (t=27.93,P =0.000); at day 7:14.67±0.49 vs.16.33 ±0.33 (t =7.81,P=0.020).TUNEL staining showed that at day 7 after ischemia,the positive cell count per mm2 in the sham operation,global cerebral ischemic and ischemic preconditioning groups were 4.83 ±1.85vs.395.67± 43.43 and 146.17± 27.38 respectively (F=23.62,P=0.001).The ischemic preconditioning group was significantly lower than that in the global cerebral ischemic group (P =0.001).Immunofluorescence staining showed that at day 7 after ischemia,the numbers of positive cells of CHOP (26.50±3.89vs.82.33±4.25; P=0.000),GRP78 (15.00±2.02vs.35.67±2.99; t=0.000),and caspase-12 (22.33 ± 2.76 vs.66.50± 7.25; P=0.000) in the ischemic preconditioning group were significantly less than those in the global cerebral ischemic group.Western blotting showed that at day 7 after ischemia,the expression levels of CHOP (1.22 ± 0.38 vs.3.22 ± 0.51; t =24.50,P =0.001),GRP78 (1.78 ± 0.45 vs.3.16 ± 0.76; t =14.29,P =0.005),and caspase-12 (2.89 ± 0.53 vs.5.96 ± 0.67; t =77.73; P =0.000) in the ischemic preconditioning group were significantly lower than those in the global cerebral ischemic group.Conclusions Ischemic preconditioning demonstrated a neuroprotective effect for the second lethal ischemia,its mechanism may be associated with the relief of ERS and downregulation of ERS-related protein.
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Objective To investigate the neuroprotective effect of sophocarpine against transient focal cerebral ischemia via down-regulation of the acid-sensing ion channel 1(ASICl) in rats.Methods Twenty-five SD rats were randomly allocated into sham operation,cerebral ischemia/reperfusion,and 5,10,and 20 mg/kg sophocarpine pretreatment groups (n=5 in each group).A rat focal ischemia model was induced by the intraluminal suture method.Five,10 and 20 mg/kg sophocarpine were injected intraperitoneally for pretreatrnent.2,3,5-triphenyltetrazolium chloride staining was used to detect cerebral infarct volume.TUNEL staining was used to detect apoptosis.Immunohistochemistry and Western blot were used to detect the expression of ASIC1 and ASIC2.Results The infarct volume after ischemia-reperfusion was(181.21±9.21)mm3,while the 5,10,and 20 mg/kg sophocarpine pretreatment groups were(150.12±6.19),(52.31±4.20),and(32.18±3.82)mm3,respectively;the neurological function scores in the cerebral ischemia/reperfusion group was(3.62±0.36),while the 5,10,and 20 mg/kg sophocarpine pretreatment grows were(3.15±0.36),(1.92±0.18),and(1.85±0.21),respectively;The surviving neurons only accounted for(31.2±2.8)% of the total cell number in the cerebral ischemia-reperfusion group,while they accounted for(51.2±3.7)%,(76.5±2.1)%,and(77.1±4.1)% in the 5,10,and 20 mg/kg sophocarpine pretreatnmat groups.Compared with the cerebral ischemia/reperfusion group,the cerebral infarct volume was decreased significantly in the sophocarpine pretreatrnent groups(all P<0.01),the neurological function scores were decreased significantly(all P<0.01),and the number of apoptotic cells was decreased significantly (all P<0.01).Immunohistochemistry showed that the number of ASIC-1 positive cells in the sham operation,cerebral ischemia-reperfusion,and 5,10,and 20 mg/kg sophocarpine pretreatment groups were(162.5±8.3),(165.1±5.3),(138.3±7.2),(82.1±6.3),and(69.2±5.5)/mm respectively;Western blot showed that the ASIC1 protein expression was decreased sigaificantly in the 10 and 20 mg/ky sophocarpine pretreatment groups (P<0.01),while there WaS no significant difference in the ASIC2 protein expression.Condusions Sophocarpine may play a neuroprotective role for cerebral ischemia-reperfusion injury in rats via down-regulating the expression of ASIC1 protein.
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Objective To investigate the clinical characteristics, operation time and methods for patients with central brain herniation caused by bifrontal contusions. Methods A retrospective study was performed on the medical records of patients with central brain herniation caused by bifrontal contusions admitted from January 2000 to December 2006. There were 45 males and 18 females, at age range of 20-72 years (average 43 years). The majority of the patients were victims of falls and traffic accidents. There were 29 patients treated with immediate operation and 34 with emergency operation. All the operations involved simultaneous bilateral craniectomy for decompression, including 17 patients treated with bilateral decompressive craniectomy and 46 with unilateral decompressive craniectomy. Results The prognosis was favorable in 19 patients with GOS score of 5 or 4 points, severely disabled in seven with GOS score of 3 points, vegetative in four with GOS score of 4 points and the worst in seven with GOS score of 1 point. Of all, 19 patients suffered severe mental disorders especially personality change and disturbance of intelligence. Seven patients were complicated by epilepsy and three by hydrocephalus. Conclusions Based on early clinical manifestations of central brain herniation combined with imaging manifestations, bilateral balance decompression craniectomy can reduce the mortality and morbidity and improve the cure rate of patients with central herniation caused by bifrontal brain contusions.
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The experimental study of cerebral ischemia plays an important role for understanding the pathogenesis of ischemic brain injury, but its correlation with the clinical therapeutic strategies has certain limitations. One of its main reasons is that the experimental models and methods can not or only partially repeat the pathophysiological processes of natural cerebral ischemia. In order to promote the understanding and interpretation of the experimental data, we review the commonly used experimental animal models and modeling methods and mainly elaborate the methods of current different in vivo and in vitro clinical evaluation. Based on these studies, we believe that the standardized clinical evaluations are hugely important for assessing the experimental results and clinical transformation.
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BACKGROUND: With development of modern medical sciences, the out comes after meningioma surgery cannot be fully assessed using morbidity,livability and mortality merely. Quality of life (QOL) is a health-related multivariable index, which provides integrated inf ormation associated with physiological,sychological and social adaptation status of the patients to doctors. Assessment of the QOL in meningioma patients may be one of a relatively good method for guiding surgery and reducing reoccurrence of tuOBJECTIVE: To evaluate the QOL in meningioma patients and then to provide relevant data for assessing the outcomes of meningioma surgery comprehensively.DESIGN: It was a single-sample investigation. SETTING: Neurosurgery Department, Second People's Hospital of Wuxi City of Nanjing Medical University.PARTICIPANTS: Totally 147 patients underwent meningioma surgery in the Neurosurgery Department of the Second Affiliated Hospital of Wuxi City affiliated to Nanjing Medical University between January 1995 to January 2001 were selected, 61 males and 86 females, with a male/female ratio of 2:3 and an age ranging from 5-77 years old, in average of 43 years old, and the median was 43 years old.METHODS: Based on World Health Organization Quality of Life 100item questionnaire (WHOQOL-100) and Karnofsky Performance Scale (KPS), we designed a questionnaire on QOL in patients with meningioma.Outcomes of the transverse investigation on 147 meningioma patients were compared with healthy controls. Surgery-related QOL curve was used for identifying the threshold satisfactory point of QOL. In addition, with selfcontrol, influence of surgery on QOL was assessed.MAIN OUTCOME MEASURES: Relationship between QOL and clinical histories, radiological analysis, operation grading, histological properties and reoccurrence were investigated.RESULTS: All of the 147 patients entered the statistical analysis. ①In patient with meningioma, Cronbach's coefficient was 0.9521 and the correlated coefficient was 0.8685, which suggested that QOL questionnaire for patients with meningioma had a good reliability and validity. ②QOL ≥70 represented that the patient was satisfied with the QOL. ③In patients underwent surgical treatment, their physiological functions, self-help and self-care except for psychological functions were significantly improved (P ＜ 0.001 ).CONCLUSION: Surgical treatment enables patients to get a satisfied QOL. QOL questionnaire for patients with meningioma is helpful to provide relevant data for meningioma operation.