丁苯酞对脑缺血再灌注损伤大鼠MMP-9活性和血脑屏障通透性的影响

目的探讨丁苯酞对脑缺血再灌注损伤大鼠的保护作用。方法通过线栓法制备大鼠局灶性脑缺血再灌注损伤模型,腹腔注射丁苯酞,于脑缺血再灌注后6h、12h、24h后用免疫组织化学的方法观察损伤侧脑组织MMP-9活性及基底膜成分Ⅳ型(collagenⅣ)胶原表达的变化。同时测定伊文思兰的含量观察损伤侧脑组织血脑屏障通透性。结果随缺血再灌注时间延长,MMP-9活性、EB含量逐渐增加,24h达峰,Ⅳ型胶原的表达逐渐减少,各组之间表达均具有统计学意义(P<0.05);丁苯酞处理组MMP-9活性、EB含量各个时间点明显低于缺血再灌注组,相同时间点Ⅳ型胶原的表达增加(P<0.05)。结论丁苯酞可抑制脑缺血再灌注损伤大鼠MMP-9的表达,增加基底膜Ⅳ型胶原的表达,降低血脑屏障通透性,从而发挥脑保护作用。     

大鼠局灶性脑缺血/再灌注后血脑屏障通透性改变时相的研究

目的探讨大鼠局灶性脑缺血/再灌注(I/R)后氧自由基(OFR)与血脑屏障(BBB)通透性改变的时相关系。方法成年健康SD大鼠随机分为脑缺血/再灌注组、正常组及假手术组,分别在脑缺血2h后再灌注各时间点观察脑组织EB含量,血清超氧化物酶(SOD)活力、丙二醛(MDA)含量以及脑组织基质金属蛋白酶2(MMP-2)的表达。结果OFR与脑组织EB含量有相同时相变化趋势,参与BBB通透性增高的整个过程,同期伴随MMP-2表达,且OFR峰值期与BBB通透性增高的第一高峰时相符合。结论OFR是导致BBB通透性增高的重要因素,尤其在其通透性增高的早期发挥重要作用,MMP-2激活可能是OFR损伤BBB的机制之一。     

钙拮抗剂对大鼠脑缺血后血脑屏障通透性的影响

目的 研究钙离子拮抗剂对大鼠脑缺血再灌注后血脑屏障(BBB)通透性和脑梗死灶体积的影响. 方法 插线法制作大鼠脑缺血再灌注模型.缺血2 h后再灌注.将150只大鼠按随机数字表法分尼莫地平组和对照组,每组分再灌注6h、12h、24 h、48h、72 h五个时间段,再灌注后尼莫地平组和对照组立即分别腹腔注射尼莫地平和生理盐水2 mg/kg.每12小时注射一次,用甲酰胺荧光法及透射电镜观察不同时段BBB通透性破坏的情况,TTC染色后计算梗死灶体积百分比.结果 大鼠脑缺血再灌注后BBB通透性和梗死灶体积百分比随时间延长逐渐增加.且BBB通透性的增加呈现两个高峰,第一个高峰在再灌注后12 h,第二个高峰在再灌注后48 h.尼莫地平组BBB通透性及脑梗死灶体积百分比的增加均较对照组明显,差异有统计学意义(P<0.05). 结论 脑缺血再灌注增加BBB的通透性和脑梗死灶体积百分比.再灌注后给予尼莫地平可加重这些病理变化.     

缺血再灌注大鼠脑内MMP-2、MMP-9与血脑屏障的关系

目的明确脑缺血再灌注后MMP-2、MMP-9与血脑屏障的关系。方法健康雄性SD大鼠54只,线栓法制作大鼠大脑中动脉缺血再灌注模型。应用含明胶的定量酶谱技术检测再灌注3h到7d内MMP-2、MMP-9的表达,用甲酰胺浸泡法检测大鼠脑内EB含量。结果 (1)缺血再灌注24h后,大鼠缺血侧脑内MMP-9表达明显升高,48h到达顶峰,4d后显著下降,7d后水平更低。24h组和48h组与其它各组相比,有显著性差异(P<0．05)。 0MMP-2缺血再灌注48h后明显升高,7d到达高峰,7d组大鼠缺血侧脑内MMP-2水平与3h组和24h组相比,有显著性差别(P<0．01)。(2)再灌注24h大鼠缺血侧脑内EB含量最高,显著高于3h及7d组(P<0．05),但与48h无显著差别(P>0．05)。结论缺血再灌注后出现了MMP-2、MMP-9和血脑屏障的动态变化,血脑屏障损伤与MMP-9 的升高相关,而与MMP-2关系不大。     

姜黄素对大鼠脑缺血再灌注损伤后基质金属蛋白酶MMP-2及MMP-9的影响

目的 探讨姜黄素对大鼠局灶性脑缺血再灌注损伤后的基质金属蛋白酶-9(MMP-9)及MMP-2表达及活性的影响.方法 采用线栓法制作大鼠暂时性大脑中动脉栓塞(MCAO)模型,MCAO后1h腹腔注射100mg/kg姜黄素,MCAO 2 h再灌注22h后处死动物.取患侧或对照侧端脑,提取总蛋白,采用Western blot和明胶酶谱分析方法研究MMPO及MMP-2的表达及活性.结果 Western blot和明胶酶谱分析结果均表明,姜黄素可降低脑缺血再灌注损伤所诱导的MMP-9及MMP-2蛋白的表达及其活性水平.结论 姜黄素对脑缺血再灌注损伤的保护作用机制之一可能与抑制了MMPO及MMP-2蛋白的高表达及活性增高有关.     

大鼠脑缺血/再灌注后血脑屏障通透性的改变及转移生长因子β1的表达

目的：探讨大鼠脑缺血再灌注后血脑屏障（BBB）通透性的改变以及转移生长因子β1（TGF－β1）在脑组织中的表达。方法：采用线栓法制备大鼠局灶性脑缺血再灌注模型，通过测定脑组织中伊文氏蓝（EB）含量及免疫组化法来观察TGF－β1的表达。结果：缺血2h再灌注3h,BBB 通透性开始增加，24h达高峰，72h后明显减弱。同时，TGF－β1在缺血再灌注3h开始表达，24h达高峰，持续至72h,72h后逐渐减弱。结论：脑缺血后BBB的破坏与TGF－β1的表达密切相关，提示TGF－β1参与了BBB内皮细胞破坏的修复过程。     

栀子苷预处理对脑缺血再灌注大鼠血脑屏障的保护作用

目的观察栀子苷预处理对脑缺血再灌注血脑屏障(blood brain barrier,BBB)损伤的保护作用。方法采用线栓法建立大鼠大脑中动脉缺血再灌注(middle cerebral artery occlusion/reperfusion,MCAO/R)损伤模型,设假手术组、模型组以及栀子苷预处理组。通过紫外分光光度计检测脑组织伊文思兰(Evans blue,EB)含量,观察大鼠BBB通透性改变。用免疫组化染色法观察缺血侧额叶皮质区胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)、基质金属蛋白酶-9(matrix metallopeptidase-9,MMP-9)及基质金属蛋白酶-2(matrix metallopeptidase-2,MMP-2)的阳性表达。用Western blot法检测水通道蛋白-4(Aquaporin-4,AQP4)的表达。结果 (1)再灌24 h后,大鼠脑组织EB含量明显增加,栀子苷预处理组较之于模型组EB含量降低(P<0.05);(2)模型组GFAP、MMP-9及MMP-2阳性表达与假手术组相比显著增加(P<0.01),而栀子苷预处理明显降低GFAP和MMP-9及MMP-2的表达(P<0.01;P<0.05);(3)缺血再灌注损伤后AQP4的表达显著提高,栀子苷预处理下调AQP4的表达(P<0.05)。结论栀子苷预处理对大鼠脑缺血再灌注引起的BBB损伤具有保护作用。     

大鼠脑缺血/再灌注后血脑屏障通透性的改变及转移生长因子β_1的表达

目的　探讨大鼠脑缺血再灌注后血脑屏障 (BBB)通透性的改变以及转移生长因子 β1(TGF β1 )在脑组织中的表达。方法　采用线栓法制备大鼠局灶性脑缺血再灌注模型 ,通过测定脑组织中伊文氏蓝 (EB)含量及免疫组化法来观察TGF β1 的表达。结果　缺血 2h再灌注 3h ,BBB通透性开始增加 ,2 4h达高峰 ,72h后明显减弱。同时 ,TGF β1 在缺血再灌注 3h开始表达 ,2 4h达高峰 ,持续至 72h ,72h后逐渐减弱。结论　脑缺血后BBB的破坏与TGF β1 的表达密切相关 ,提示TGF β1 参与了BBB内皮细胞破坏的修复过程     

大鼠局灶性脑缺血再灌注血脑屏障超微结构及紧密连接蛋白Occludin变化的研究

目的研究大鼠局灶性脑缺血再灌注模型血脑屏障(BBB)超微结构和Occludin的变化,探讨BBB的结构改变及Occludin的表达异常在再灌注损伤中的作用。方法雄性Wistar大鼠,随机分成假手术组、缺血2h再灌注3h、12h、24h、72h组,应用透射电镜、RT-PCR、免疫组化和Western Blot等方法观察再灌注后不同时相缺血区皮质BBB的超微结构,Occludin mRNA和蛋白水平的变化。结果局灶性脑缺血再灌注后,缺血区皮质BBB的超微结构受损,Occludin mRNA和蛋白表达水平下调。上述变化开始于再灌注后3h,再灌注24h达到高峰,72h开始减弱。结论脑缺血再灌注过程中,BBB的超微结构损伤及Occludin的表达下降加重了缺血再灌注损伤。     

大鼠局灶性脑缺血后再灌注期caspase—9 mRNA及Apaf—1mRNA表达的动态变化

目的探讨大鼠局灶性脑缺血后再灌注期caspase-9 mRNA及Apaf-1 mRNA表达的动态变化.方法采用线栓法制作大鼠局灶性脑缺血后再灌注模型,以逆转录聚合酶链式反应(RT-PCR)技术检测caspase-9 mRNA及Apf-1 mRNA的表达.结果缺血2 h后再灌注,缺血皮质中caspase-9 mRNA的表达在再灌注后24h达高峰,48h仍保持高水平,而Apaf-1 muRNA的表达无明显改变.结论局灶性脑缺血后再灌注48h内caspase-9 mRNA表达增强.     

Update on the language disorders of individuals on the autistic spectrum

Inadequate language is a defining feature of the autism spectrum disorders (autism). Autism is a behaviorally and dimensionally defined developmental disorder of the immature brain that has a broad range of severity and many etiologies, with multiple genes involved. Early studies, which focused on the language of verbal children on the autistic spectrum, emphasized aberrant features of their speech such as unusual word choices, pronoun reversal, echolalia, incoherent discourse, unresponsiveness to questions, aberrant prosody, and lack of drive to communicate. Persistent lack of speech of some individuals was attributed to the severity of their autism and attendant mental retardation rather than possible inability to decode auditory language. Clinical study of unselected children with autism indicated that the language deficits of preschoolers fall into two broad types, perhaps with subtypes, those that involve reception and production of phonology (sounds of speech) and syntax (grammar), and those that do not but involve semantics (meaning) and pragmatics (communicative use of language, processing, and production of discourse). Except for the preschoolers' universally deficient pragmatics and comprehension of speech, many of their language deficits parallel those of non-autistic preschoolers with developmental language disorders. There is now biological support for the clinical observation that young autistic children are language disordered as well as autistic. Recent electrophysiological studies disclose auditory input abnormalities in lateral temporal cortex even in verbal individuals on the autistic spectrum. Severe receptive deficits for phonology enhance the risk for epilepsy. Genetic studies indicate that linkage to chromosome 7q31-33 is limited to families with evidence for phonologic impairment as well as autism. Clearly, social and cognitive disorders alone provide an inadequate explanation for the range of language deficits in autism.     

Evaluation trial on the efficacy of neuroleptics on the outcome of schizophrenia]

Feasible and ideal methodological conditions lacking, we have tried an evaluation concerning the efficacy of neuroleptics upon the course of schizophrenia by comparing the evolution of homogeneous studies before and since the neuroleptic period. On the short term, neuroleptics are significantly more effective than the placebo upon schizophrenic symptoms and prevent the relapses in an noteworthy manner. On the long term, the evolution is significantly better for follow-up studies treated by neuroleptics (60% of patients improved) than for the non-treated follow-up studies i.e. before neuroleptic period (27.5% of patients improved). The time of the follow-up has an effect on the course of schizophrenia. Before neuroleptic periods, the schizophrenic process beyond 6 to 10 years was either stabilized or worsened. On the contrary, since the neuroleptic period, the number of improvements continued to increase after 12 years time (79.5% of patients improved for the follow-up beyond 12 years time versus 60% under 12 years). These improvements include paranoid and hebephrenic forms. On the contrary, catatonic forms had decreased very much since the utilization of neuroleptics (they moved from 18 to 28% before neuroleptic periods to 2% after the beginning of utilization of neuroleptics). If neuroleptics have undeniable action upon the schizophrenic symptomatology, they also act, on the long term, upon the social course of schizophrenia (30% of social remission before neuroleptic period versus 50% since neuroleptic period).