^1H-magnetic resonance spectroscopy screening for animals with acute cerebral infraction suitable forthrombolytic therapy

BACKGROUND: As a non-invasive technique which can provide comprehensive biological information, 1H-magnetic resonance spectroscopy (1H-MRS) may provide valuable reference data for irreversible recovery or reversible changes in ischemic tissue after stroke. OBJECTIVE: To monitor and evaluate the effect of the urokinase thrombolytic therapy after experimental acute cerebral ischemia by 1H-MRS technology and investigate its adaptability. DESIGN: Randomly controlled animal study. SETTINGS: Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science. MATERIALS: Eleven healthy adult Sprague-Dawley (SD) rats, weighing 260–300 g and of both genders, were supplied by Experimental Animal Center of Tongji Medical Collage, Huazhong University of Science and Technology [SCXK (e) 2004-007]. 4.7T superconducting nuclear magnetic resonance meter was provided by Brucker Company. METHODS: The experiment was carried out in Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science from August 2003 to December 2005. ① The rats were randomly divided into 30-minute self-thrombo-embolism group (n =6) and 60-minute self-thrombo-embolism group (n =5). Six rats in 30-minute self-thrombo-embolism group were occluded with clot embolus for 30 minutes and 5 rats in 60-minute self-thrombo-embolism group were occluded for 60 minutes. 10 000 U/kg urokinase was dissolved in 2 mL saline and the operation lasted for 5 minutes. ② 1H-MRS was performed before thrombolysis and at 3 hours and 24 hours after successful embolization. The metabolic changes of N-acetyl-L-aspartic acid (NAA)/phosphocreatine (PCr) + creatine (Cr), choline phosphate (Cho)/PCr+Cr and lactic acid (Lac)/PCr+Cr in the region of interests were analyzed. ③ The T2W image was conducted 24 hours after the thrombolytic therapy with TR=500 ms and TE=25 ms. ④ The subjects were sacrificed immediately after 1H-MRS and the brain tissues were cut into pieces and stained with HE method; in addition, pathological changes were observed under optic microscope. MAIN OUTCOME MEASURES: ① Metabolic changes of NAA/PCr+Cr, Cho/PCr+Cr and Lac/PCr+Cr in the region of interests; ② T2W image at 24 hours after the thrombolysis; ③ pathological observation of brain tissue. RESULTS: Eleven rats were all involved in the final analysis. ① Metabolic changes in the region of interests : In 30-minute self-thrombo-embolism group, the Lac peak emerged immediately after the embolism, but the ischemic zone decreased 3 hours after the thrombolytic therapy (0.252±0.01, 0.603±0.01, P < 0.01). Lac/(PCr+Cr) ratio was 0.290±0.01 at 24 hours after thrombolysis, which was higher than that at 3 hours after thrombolysis (P < 0.01). The NAA/ (PCr+Cr) ratio decreased significantly at 3 hours after the thrombolysis as compared with that before thrombolysis (0.922±0.16, 1.196±0.01, P < 0.05). In 60-minute self-thrombo-embolism group, the Lac/(PCr+Cr) ratio was higher at 3 hours after thrombolysis than that before thrombolysis (0.846±0.12, 0.601±0.11, P < 0.05) and the NAA/(PCr+Cr) decreased at 3 hours after the embolism. Fluctuation of NAA/ (PCr+Cr) ranged from 0.68 to 0.75 before thrombolysis and from 0.71 to 0.75 at 3 hours after thrombolysis. ② T2W image: T2W image showed that 2 subjects in 30-minute self-thrombo-embolism group whose Lac/NAA was higher than 0.7 suffered from intracranial hemorrhage. This meant that the subjects with Lac/NAA > 0.7 were more likely to suffer from intracranial hemorrhage. ③ Histological and morphological examinations: Optic microscope demonstrated that interspace surrounding nerve cells was widened at ischemic center; neurons were swelling; nucleus was stained lightly; pyknosis and mesenchymal edema were mainly observed in lateral cortex of brow and vertex and in lateral part of corpus striatum. CONCLUSION: ①Compound parameters in ischemic area before thrombolysis should be regarded as an important predicting marker for thrombolytic therapy, effect evaluation and termination. ② 1H-MRS combining with other imaging technique is a detecting way for screening cases who are suitable for thrombolytic therapy.     

缺氧诱导因子-lα与脑缺氧缺血性损伤

缺氧诱导因子-lα（hypoxia-inducible factor-1alpha，HIF-lα）是近来发现的广泛存在于哺乳动物和人体内的一种缺氧应答调控因子，在调节缺氧诱导的基因表达中起关键性作用。它可调节表达多种靶基因如血管内皮生长因子、促红细胞生成素等，对改善脑缺氧缺血后能量代谢障碍、促进脑血流动力学恢复、抑制兴奋性氨基酸毒性、减少细胞凋亡等起重要作用。通过进一步对HIF-lα及其靶基因的研究，可能为临床治疗脑缺氧缺血性损伤提供了一种新的治疗策略。     

近视性屈光参差的功能性磁共振成像研究

目的利用血氧水平依赖性功能性磁共振成像(BOLD-fMR I)技术,探索人类近视性屈光参差是否对大脑皮层功能和结构造成影响。方法采用无磁MR I专用眼镜纠正屈光不正,以1.5T磁共振成像系统采集8例近视性屈光参差者枕叶视皮层兴趣区BOLD-fMR I数据,比较双眼皮层激活部位及范围的不同,及视力较差眼屈光纠正前后皮层激活情况的变化,分析其改变特点及机制。结果矫正屈光基础上,近视性屈光参差者双眼激活范围没有明显差异(P>0.05);视力较差眼屈光矫正前后皮层激活范围有明显差异(P<0.05)。结论人类近视性屈光参差可能没有发生明显的皮层功能损害及优势眼的转移;配镜可明显提高视力较差眼的皮层激活,应尽早配镜或手术矫正。     

急性脑血管病病人应激状态的临床特点及护理

[目的 ]分析急性脑血管病(ACVD)应激状态的临床特点 ,探讨防治策略及护理对策。 [方法 ]回顾分析 3 62例ACVD病人的临床资料。[结果 ]ACVD病人应激反应的发生率为 47.5 1% ,病死率为 11.88%。 [结论 ]早期明确诊断与治疗 ,并采取措施积极调控机体应激状态 ,加强护理 ,有助于控制病情和促进康复 ,降低病死率。     

胰岛素抵抗和脑血管病关系的研究

目的：探讨胰岛素抵抗与脑梗死、脑出血的关系，为针对胰岛素抵抗的治疗可以有效地预防脑血管疾病提供理论依据。方法：选取42例脑梗死（脑梗死组）、40例脑出血（脑出血组）及30例非脑血管病患者（对照组），分别测定空腹胰岛素（FINS）、空腹血糖（FBG），计算胰岛素敏感指数（ISI），各组间进行比较。结果：脑梗死组和脑出血组患者ISI低于对照组（P〈0.05），而FINS高于对照组（P〈0．05），FBG与对照组差异无统计学意义（P〉0．05）。结论：胰岛素抵抗可能是脑血管病的一个重要危险因素。     

脑源性神经生长因子和神经干细胞联合移植对大脑中动脉阻塞大鼠神经功能恢复的作用

目的 将脑源性神经生长因子(BDNF)和神经干细胞(NSCs)单独及联合移植应用于大脑中动脉阻塞(MCAo)模型大鼠,观察BDNF和NSCs移植对大鼠缺血性脑卒中神经功能恢复的作用及BDNF对内源性和外源性NSCs增殖、迁移及分化的影响.方法 体外分离、培养新生大鼠海马NSCs,BrdU标记.实验动物随机分为A组(MCAo组);B组(MCAo+BDNF组);C组(MCAo+NSCs组);D组(MCAo+BDNF+NSCs组),每组16只,移植后进行神经功能损害评分(NSS),用免疫组织化学行BrdU、nestin、BrdU/NSE检测,分析结果.结果 移植后的2、4周神经功能评分分别为:A组5.3±0.5、5.3±0.5;B组4.0±0.8、3.8±0.5;C组3.5±0.6、3.5±0.6;D组2.0 ±0.8、1.8±1.0,D组显著好于其他3组(P<0.05),B组与c组显著好于A组(P<0.05).nes.tin阳性细胞数:A组1.24±1.13,B组2.59±1.44(P<0.05),BrdU阳性细胞数:A组0.52±0.68,B组1.65±1.10(P<0.05).BrdU阳性细胞数:C组6.08±1.52,D组10.26±1.96(P<0.05),BrdU/NSE双阳性细胞数:C组1.74±1.04,D组3.58±1.20(P<0.05).结论 BDNF和NSCs移植单独及联合应用对MCAo大鼠的神经功能恢复均有作用,两者联合具有协同作用.BDNF对内源性NSCs的激活、增殖有促进作用,对外源性NSCs的增殖、迁移及分化有促进作用.