高压氧对缺血再灌注小鼠脑组织细胞因子IL-10及血脑屏障通透性的影响

目的：探讨高压氧（HBO）对缺血再灌注小鼠脑组织中细胞因子IL-10含量、mRNA的表达、血脑屏障（BBB）通透性的影响。方法：复制清醒小鼠脑缺血再灌注模型，并于再灌注期间行0．25MPa（CBFATA）HBO治疗5次，在处死动物前1h经尾静脉注射2％伊文思兰（Evansblue，EB），采用比色法、ABC—ELISA、RT—PCR分别检测脑组织中细胞因子IL-10含量、mRNA的表达及EB的含量的变化。结果：脑组织EB的渗出于缺血再灌注后第4h为最多，于再灌注后第11h、23h、48h、72h逐渐下降；HBO＋脑缺血再灌注组脑组织EB的渗出与相应时间的脑缺血再灌注组相比明显降低（P〈0．01）。HBO组脑组织EB的渗出与相应时间的假手术组相比变化不明显（P〉0．05）。脑缺血再灌注组细胞因子IL-10含量于再灌注11h开始增加并于再灌注23h达到高峰，再灌注48h、72h逐渐下降。脑缺血再灌注组细胞因子IL-10含量与相应时间的假手术组相比于再灌注后11h、23h、48h、72h都明显增高（P〈0．01）。HBO＋脑缺血再灌注组细胞因子IL-10含量于再灌注后11h、23h、48h、72h与相应时间的脑缺血再灌注组相比变化不明显（P〉0．05）；而IL-10mRNA的表达明显增加（P〈0．01）。HBO组与相应时间的假手术组相比IL一10含量和mRNA的表达变化都不明显（P〉0．05）。结论：HBO从基因水平可明显增加脑缺血再灌注72h细胞因子IL-10mRNA的表达，从而具有保护血脑屏障的作用；HBO对正常脑组织中IL-10含量、mRNA的表达作用不明显。     

高压氧对急性损伤期缺血再灌注大鼠脑内水通道蛋白-4表达的影响

【目的】研究水通道蛋白－4（AQP4）在缺血／再灌注脑损伤大鼠脑内的表达,及高压氧（hyperbaric oxygen,HBO）对其表达的影响。【方法】将135只SD大鼠分为假手术对照组（Sham组）、缺血再灌注组（I／R组）和高压氧处理组（HBO组）,以四动脉阻断法建立全脑缺血再灌注大鼠模型。I／R组和HBO组按再灌注的时间不同分为四个亚组,每组15只,即动物缺血20min后分别再灌注6h、24h、3d和5d,HBO各亚组在再灌注后分别行不同次数的高压氧处理。测定脑组织含水量及伊文斯蓝含量,并采用免疫组织化学技术检测AQP4的表达。同时观察HB0对脑水肿和AQP4表达的影响。【结果]Sham组AQP4表达较低,在缺血损伤后表达升高,脑组织含水量及伊文斯蓝含量增加,给予HB0后AQP4的表达和脑组织含水量降低。【结论】缺血／再灌注脑损伤后AQP4表达上升,脑水肿明显,给予HB0可抑制AQP4的表达,减轻脑水肿。     

高压氧对急性损伤期全脑缺血再灌注大鼠脑内兴奋性氨基酸水平的影响

目的：探讨高压氧（HBO）对缺血再灌注脑内兴奋性氨基酸水平的影响。方法：将SD大鼠分为缺血再灌注组（I／R组）、高压氧处理组（HBO组）及似手术对照组（Sham—O组），以四动脉阻断法建立全脑缺血再灌注大鼠模型。动物缺血20min后分别再灌注6h、24h、48h和96h，各HBO组在再灌注后分别行不同次数的高压氧处理。取动物的全脑测定谷氨酸（Glu）和天门冬氨酸（Asp）含量。结果：24h和48hHBO组Glu水平明显低于对应时间点的I／R组（P＜0．01），且24hHBO组Asp含量也低于I／R组（P〈0．05），而各时间点I／R组的Glu水平均高于Sham—O组（P〈0．01）。结论：在一定时间内进行高压氧处理町抑制由全脑缺血再灌注所诱导的兴奋性氨基酸的过度释放，这可能是高压氧治疗缺血再灌注脑损伤的机制之一     

左旋四氢巴马汀在大鼠全脑缺血-再灌流时对脑组织电解质含量的影响

目的：通过观察脑缺血－再灌流时脑组织钙、镁、锌、钠、铁含量的变化，探讨左旋四氢巴马汀在全脑缺血－再灌流损伤时的作用机制。方法：建立大鼠急性脑缺血－再灌流损伤模型，用原子分光光度仪检测脑组织电解质含量。结果：与假手术组比较脑缺血－再灌流12h组钙、锌、钠、钾含量增高（P＜0．01），铁含量亦增高（P＜0．05），镁含量降低（P＜0．01）；24h钙、锌、钠含量进一步增高（P＜0．01），镁含量进一步降低（P＜0．01），钾和铁含量与假手术组接近（P＞0．05）。左旋四氢巴马汀在脑缺血再灌流12h和24h均能抑制脑组织钙（P＜0．01）、锌（P＜0．01）、钠（P＜0．05，P＜0．01）含量的上升，并提高脑组织镁（P＜0．01）和钾（P＜0．05，P＜0．01）的含量，降低铁含量（P＜0．05，P＜0．01）。结论：左旋四氢巴马汀可抑制脑缺血－再灌流期间脑组织钙、锌、钠含量的上升并提高镁和钾含量，降低铁含量。     

短暂性全脑缺血再灌注大鼠经高压氧治疗后脑组织神经节苷脂的变化

背景：神经节苷脂是神经组织中含量丰富并可发挥神经保护作用的含唾液酸的鞘糖脂，在脑缺血或缺氧性疾患时有含量或组分的变化。 目的：通过观察全脑缺血再灌注大鼠应用高压氧治疗后脑组织神经节苷脂的变化情况，探讨高压氧对缺血再灌注损伤治疗作用的可能途径。 设计：随机一对照观察。 单位：首都医科大学附属朝阳医院高压氧科和首都医科大学基础医学院生物化学与分子生物学系。 材料：动物模型制作于2002—03／04在首都医科大学附属朝阳医院高压氧科（北京市重点实验室）完成，各项指标检测在首都医科大学基础医学院生物化学与分子生物学系完成。选择雌性SD大鼠54只，将大鼠随机分成9组，即假手术组、缺血再灌注6h，24h，48h，96h组及高压氧6h，24h，48h，96h组，每组6只。 方法：除假手术组外，其余8组大鼠均建立脑缺血再灌注动物模型，按四动脉阻断法建立，缺血20min后再通。假手术组同样手术但不阻断动脉。将高压氧组大鼠置于实验舱内，纯氧洗舱5min，升压5min至0．1MPa后稳压，吸纯氧45min，减压10min。高压氧组大鼠在缺血再灌注3h后行高压氧处理1次，24h，48h及96h组在每天同一时间行高压氧处理1次。缺血再灌注组和假手术组处于常压空气环境中。再灌注组和高压氧处理组大鼠分别于再灌注6h，24h，48h及96h麻醉取全脑标本测定总神经节苷脂及各组分百分含量，神经节苷脂各组分以高效薄层层析法测定。 主要观察指标：各组大鼠全脑组织神经节苷脂的总含量及其各组分的百分含量。 结果：54只大鼠全部进入结果分析．无脱失。①高压氧24h及48h组总神经节苷脂均显著高于假手术组及相应缺血再灌注时相组（F=12．730，122．246，P〈0．01），但缺血再灌注各时相组与假手术组相比，差异均无显著性意义（P〉0．05）。②对缺血再灌注24h组大鼠GT1b相对含量显著低于假手术组（F=13．575，P〈0．01），再灌注48h组GD1b及GM1分别低于假手术组（F=4．015，3．979，P〈0．05），GM3于再灌注24h高于假手术组及其他时相组（F=21．450，P〈0．01），并于再灌注96h反弹。③高压氧24h组GM1，GM3分别高于假手术组（F=3．970，21．450，P〈0．05，〈0．01），GD1a、GD1b和GT1b均低于假手术组（F=13．575，5．745，8．783，P〈0．05-0．01），但GT1b明显高于缺血再灌注各相应时相组（F=8．783，P〈0．05）。 结论：大鼠短暂全脑缺血再灌注后可引起神经节苷脂总含量、GT1b，GD1b，GM1百分含量降低及GM3百分含量升高，其中提高脑组织神经节苷脂总量、GM1含量及加速GT1b的恢复可能为高压氧治疗改善缺血性脑损伤的作用途径，而GD1a，GD1b百分含量的下降有何作用尚不清楚。     

川芎嗪注射液抗脑缺血—再灌注损伤作用机制的实验研究

目的：探讨川芎嗪注射液（LGTI）对脑缺血－再灌注损伤（CIRI）的防治作用及其机制。方法：制备家兔CIRI模型,随机分为假手术对照组、缺血－再灌流组和LGTI组,动态观察浆及脑组织一氧化氮（NO）水平,内皮素（ET）含量,丙二醛（MDA）浓度,超氧化物歧化酶（SOD）尖性及脑超微结构伯变化。结果：脑缺血－再灌注期间,血浆和脑组织NO水平及SOD活性与缺血前比较明显下降（P＜005和P＜0．01）,ET及MDA含量与缺血前比较显著升高（P＜0．05和P＜0．01）,超微结构发 生异常改变;使用LGTI后,上述各指标的异常变化明显减轻,与缺血－再灌注相相比差异有显著意义,（P＜0．01）。结论LGTI具有良好的防护作用,其机制与提高机体NO水平、降低ET水平及减轻氧自由的基损伤等有关。     

黄芪对沙土鼠脑缺血再灌注损伤的影响

目的：研究黄芪对沙土鼠脑缺血－再灌注损伤的影响。方法：结扎沙土鼠双侧颈总动脉致脑缺血15分钟再灌注48小时,造成脑组织迟发型神经元死亡（DND）模型,比较假手术组、模型组和黄治疗组鼠脑组织中Na^ -K^ -ATP酶酶活性,一氧化氮合酶（NOS）活性、一氧化氮（NO）和兴奋性氨基酸含量的变化。结果：（1）与假手术组比较,模型组和黄芪治疗组鼠脑组织中Na^ -K^ -ATP酶酶活性均明显降低,但模型组比苋芪治疗组降低更明显（P均＜0．01）。（2）各组鼠脑组织乳酸（LD）含量变化未见统计学差异。（3）与假手术组比较,模型且和苋芪治疗组鼠脑组织NOS活性和NO含量均降低,但模型组降低更明显（P＜0．05）。（4）与假手术组比较,模型组和黄芪治疗组脑组织谷氨酸（Glu)含量均高于假手术组,但模型组的升高更明显（P＜0．05）。（5）模型组和黄芪治疗组脑组织天冬氨酸（Asp)含量均高于假手术组（P均＜0．05）。模型组Asp含量略高于黄芪治疗组,但差异无显著性。（6）各组脑组织γ氨丁酸（γ-GABA）和甘氨酸（Gly)含量的比较差异无显著性。结论：黄芪抗脑缺血－再灌注损伤的机制可能还与其防止脑缺血后脑组织Na^ -K^ -ATP酶知性、NOS活性、NO合成量的降低及兴奋性氨酸含量的升有高关。     

高压氧对缺血再灌注小鼠脑组织MMP-9﹑MMP-2mRNA的表达及血脑屏障通透性的影响

目的探讨高压氧（HBO）对缺血再灌注小鼠脑组织中基质金属蛋白酶（MMPs）MMP-9、MMP-2 mRNA的表达及血脑屏障通透性的影响。 方法复制清醒小鼠脑缺血再灌注模型，并于再灌注期间行0.25 MPa HBO治疗5次，在处死动物前1h经尾静脉注射2%伊文蓝（EB）,采用逆转录多聚酶链反应（RT-PCR）方法及比色法分别检测脑组织中MMP-9、MMP-2 mRNA的表达及EB的含量。 结果脑缺血再灌注组MMP-9、MMP-2 mRNA的表达及EB的含量明显高于假手术组，差异有统计学意义（P<0.01），高压氧组与假手术组比较，脑组织中MMP-9、MMP-2 mRNA的表达及EB的含量相近（P&rt;0.05），HBO+脑缺血再灌注组脑组织中基质金属蛋白酶MMP-9、MMP-2 mRNA的表达及EB的含量明显低于脑缺血再灌注组，差异有统计学意义（P<0.01）。 结论高压氧可明显减少脑缺血再灌注脑组织中基质金属白蛋酶MMP-9、MMP-2的表达，具有降低血脑屏障通透性的作用。     

高压氧对急性脑缺血再灌注小鼠AQP-4表达及血脑屏障通透性的影响

目的:探讨高压氧(HBO)对缺血再灌注小鼠脑组织中水通道蛋白-4 mRNA(AQP-4)的表达及血脑屏障通透性的影响。方法:复制清醒小鼠脑缺血再灌注模型,并于再灌注期间行0.25MPa HBO治疗5次,采用逆转录多聚酶链反应(RT-PCR)方法、比色法及干湿法分别检测脑组织中AQP-4 mRNA的表达、伊文思蓝(EB)的含量及脑组织含水量。结果:脑缺血再灌注组AQP-4 mRNA的表达、EB的含量及脑组织含水量明显高于假手术组,差异有显著性意义(P<0.01)。高压氧组与假手术组相比,脑组织中AQP-4 mRNA的表达、EB的含量及脑组织含水量变化无显著性差异。HBO 脑缺血再灌注组脑组织中AQP-4 mRNA的表达、EB的含量及脑组织含水量较脑缺血再灌注组明显降低,差异有非常显著性意义(P<0.01)。结论:高压氧可通过降低脑缺血再灌注中AQP-4 mRNA的表达,降低血脑屏障的通透性,减轻脑水肿。     

局灶性脑缺血再灌注后白细胞介素—6，肿瘤坏死因子—β的表达及川芎嗪对其表达的影响

目的：探讨大鼠局灶性脑缺血再灌注后各时相的白细胞介素－6（IL－6），肿瘤坏死因子－α（TNF－α）的表达及中药川芎嗪对其表达的影响。方法：采用放免法测定IL－6，TNF－α的动态变化。结果：对照组IL－6表达在12h时显增高（P＜0．05），实验组在再灌注6h时表达显增高（P＜0．05），12h时仍显增高（P＜0．05），对照组TNF－α缺血早期表达即增高，再灌注12h时最显，而实验组明显降低（P＜0．05）。结论：TNF－α加重脑缺血再灌注损伤，IL－6作为一种脑缺血后神经细胞死亡的内生拮抗剂，起到神经保护作用，种芎嗪可抑制脑缺血再灌注后TNF－α的表达，使IL－6的表达提前，可能是川芎嗪对抗脑缺血再灌注损伤的机制之一。     

Abnormal brain activity in prefrontal brain regions in abstinent marijuana users

We used PET (15)O and a modified version of the Stroop task to determine if 25-day abstinent heavy marijuana (MJ) users have persistent deficits in executive cognitive functioning (ECF) and brain activity. Performance on a modified version of the Stroop task and brain activity was compared between 25-day abstinent, heavy marijuana users (n = 11), and a matched comparison group (n = 11). The 25-day abstinent marijuana users showed no deficits in performance on the modified version of the Stroop task when compared to the comparison group. Despite the lack of performance differences, the marijuana users showed hypoactivity in the left perigenual anterior cingulate cortex (ACC) and the left lateral prefrontal cortex (LPFC) and hyperactivity in the hippocampus bilaterally, when compared to the comparison group. These results suggest that marijuana users display persistent metabolic alterations in brain regions responsible for ECF. It may be that marijuana users recruit an alternative neural network as a compensatory mechanism during performance on a modified version of the Stroop task. These differences in brain activity may be a common denominator in the evolution of maladaptive behaviors such as substance abuse and other neuropsychiatric disorders.     

脑胶质瘤中肿瘤干细胞的体外傲射敏感性

背景：目前放疗治疗脑胶质瘤效果不理想,可能因素有很多.目的：探讨脑胶质瘤中肿瘤干细胞的体外放射敏感性.方法：取脑胶质瘤细胞,接种于含生长因子的无血清培养基中培养,取细胞活力最强的位点扩增3-5代的肿瘤球细胞,给予不同X射线剂量照射,检测其细胞活力,以确定最适的放疗剂量.结果与结论：胶质瘤中不同部位的肿瘤细胞增殖活力有差异;8 Gy以上X射线剂量对脑肿瘤干细胞具有显著的杀伤作用.说明脑胶质瘤具有异质性,部位不同,脑肿瘤干细胞增殖活力不同;不同的放疗剂量对脑肿瘤干细胞有不同的影响.     

Effect of brain cooling on brain ischemia and damage markers after fluid percussion brain injury in rats

Although systemic cooling had recently been reported as effective in improving the neurological outcome after traumatic brain injury, several problems are associated with whole-body cooling. The present study was conducted to test the effectiveness of brain cooling without interference with the core temperature in rats after fluid percussion traumatic brain injury (TBI). Brain dialysates ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and injury (e.g., glycerol) markers before and after TBI were measured in rats with mild brain cooling (33 degrees C) and in the sham control group. Brain cooling was accomplished by infusion of 5 mL cold saline via the external jugular vein under general anesthesia. The weight loss was determined by the difference between the first and third day of body weight after TBI. The maximum grip angle in an inclined plane was measured to determine motor performance, whereas the percentage of maximal possible effect was used to measure blockade of proprioception. The triphenyltetrazolium chloride staining procedures were used for cerebral infarction assay. As compared with those of the sham-operated controls, the animals with TBI had higher values of extracellular levels of glutamate, lactate-to-pyruvate ratio, and glycerol in brain and intracranial pressure, but lower values of cerebral perfusion pressure. Brain cooling adopted immediately after TBI significantly attenuated the TBI-induced increased cerebral ischemia and injury markers, intracranial hypertension, and cerebral hypoperfusion. In addition, the TBI-induced cerebral infarction, motor and proprioception deficits, and body weight loss evaluated 3 days after TBI were significantly attenuated by brain cooling. We successfully demonstrate that brain cooling causes attenuation of TBI in rats by reducing cerebral ischemia and injury resulting from intracranial hypertension and cerebral hypoperfusion. Because jugular venipuncture is an easy procedure frequently used in the emergency department, for preservation of brain function, jugular infusion of cold saline may be useful in resuscitation for trauma patients.     

Fatigue scores in patients with brain metastases receiving whole brain radiotherapy

Purpose

Whole brain radiotherapy (WBRT) is a treatment strategy used commonly to relieve burdensome symptoms and improve quality of life (QOL) in patients with multiple brain metastases. The purpose of this study is to determine changes in fatigue score following WBRT as it is a common symptom experienced in this population.

Methods

Fatigue and overall QOL scores were collected prospectively in patients for up to 3 months post-WBRT by several questionnaires at different times including the following: Edmonton Symptom Assessment System (ESAS), Brain Symptom and Impact Questionnaire (BASIQ), Spitzer Questionnaire, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), EORTC brain module (EORTC QLQ-BN20?+?2), EORTC QLQ-C15-PAL, and Functional Assessment of Cancer Therapy—General (FACT-G). Questionnaires were grouped for analysis by Wilcoxon Signed Rank test according to the scale of ranking into 0–10, 1–4, and 0–4.

Results

Thirty-six patients were interviewed with the ESAS or BASIQ. The median age was 65 years old, and median Karnofsky Performance Status (KPS) was 70. There was a significant increase in fatigue score from baseline to month 1 (p?=?0.02), and months 2 and 3 had no significant change. There was a significant correlation between fatigue and overall QOL score at baseline and month 1 (p?=?0.01, p?<?0.0001), respectively. Two hundred and twenty-eight patients were surveyed with Spitzer, C15-PAL, BN20?+?2, QLQ-C30, or FACT-G. Median age was 64 years old and median KPS was 80. Compared to baseline, fatigue score was significantly higher at month 1 (p?<?0.0001) and month 2 (p?=?0.001), with no significant change at month 3. Significant correlation was found between fatigue and overall QOL at baseline, months 1, 2 (p?<?0.0001), and 3 (p?=?0.0009). For all groups, there was no significant change in fatigue score between patients with or without dexamethasone (Dx), except for the fatigue changed score of the group with scale 0–4.

Conclusions

Fatigue was significantly increased from baseline to month 1 in all patients, and most patients experienced no difference in fatigue if they were receiving Dx. Increased fatigue was significantly related with decreased overall QOL.     

Gender differences in partial-volume corrected brain perfusion using brain MRI in healthy children

To investigate gender differences in brain perfusion, this study utilized pulsed arterial spin-labeling magnetic resonance imaging (MRI) in a large number of healthy children. Data on structural and perfusion MRI in the brain were collected from 202 healthy children aged 5-18 years. Gender differences in brain perfusion using partial volume correction (PVC), which was calculated by dividing the normalized perfusion MRI by the normalized gray-matter segments, were analyzed by applying voxel-based analysis and region-of-interest (ROI) analysis. Girls showed significantly higher brain perfusion with PVC in the bilateral medial aspect of the parietal lobes, including the posterior cingulate cortex and precuneus, as compared to boys using voxel-based analysis. In addition, brain perfusion with PVC in the bilateral posterior cingulate cortex, bilateral precuneus, and left thalamus was significantly higher in girls than in boys in the ROI analysis. In contrast, no regions were seen in which boys exhibited higher brain perfusion with PVC than girls in both analyses. The findings showed significant differences between boys and girls in brain perfusion with PVC, and these differences may contribute to gender differences in the cognitive ability of healthy children.