老年与青壮年外伤性迟发脑内血肿的临床对比分析

目的 探讨老年人与青壮年外伤后迟发脑内血肿的临床特点。方法回顾性分析我院近四年来收治的56例迟发脑内血肿，按年龄分为15～50岁青壮年组，51～86岁老年组，观察对比两组入院时GCS、迟发脑内血肿的时间以及病死率。结果老年组的GCS与是否发病无显著性差异（P〉0.05），两组间迟发脑内血肿的时间无显著性差异（P〉0．05），老年组死亡率高达56．25％，青壮年组死亡率为27．5％。结论（1）老年人颅脑损伤后入院时GCS不能作为判断其是否发生迟发脑内血肿的依据；（2）青、老年人颅脑损伤后出现迟发脑内血肿的时间无明显差别；（3）老年人外伤性迟发脑内血肿的病死亡率较高。     

大鼠颅脑损伤后亚低温治疗对Calpain及作用底物MAP-2表达的影响

目的探讨亚低温治疗对颅脑损伤后Calpain、MAP-2基因和蛋白表达的影响。方法将54只SD大鼠随机分为假手术组（n=6）、常温脑损伤组（n=24）和亚低温脑损伤组（n=24）。亚低温脑损伤组在液压打击伤后即接受持续4h的亚低温治疗。伤后6h、12h、24h和72h4个时间点分别处死3只常温脑损伤组和亚低温脑损伤组大鼠。荧光PCR、Western blot半定量检测皮质Calpain及MAP-2基因转录和蛋白的表达。结果颅脑损伤后12h及24h亚低温使Calpain mRNA表达增加（P〈0．05）,伤后6h、12h、24h和72h亚低温均可减少Calpain蛋白的升高,伤后12h及72h尤其显著（P〈0．05）。与假手术组比较,常温脑损伤组和亚低温脑损伤组MAP-2基因转录均减少（P〈0．05）;与常温脑损伤组比较,伤后6h、12h和24h亚低温可抑制MAP-2基因转录的下调,但亚低温脑损伤组MAP-2蛋白的表达均比同时间点常温组低（P〈0.05）。结论颅脑损伤后亚低温治疗的脑保护机制可能与调节Calpain蛋白的表达有关,而亚低温与MAP-2的关系还有待进一步研究。     

血管内皮细胞生长因子的表达对创伤后脑组织含水量的影响

目的探讨颅脑创伤后挫裂伤脑组织中血管内皮细胞生长因子（vascularendothelialgrowth{actor,VEGF）的表达与颅脑创伤后继发脑水肿的关系。方法选用成年、健康、雄性Wiste大鼠60只,随机分为实验组和对照组。前者按损伤后不同时间点分为3h、72h、7d组,每组15只大鼠。我们采用Marmarou自由落体撞击法建立局灶性脑挫裂伤动物模型,实验组大鼠损伤后按预定的时间点断头处死,开颅切除损伤及邻近损伤区标本,而对照组则不致伤,监测内容同损伤组。采用免疫组化技术（SP法）及显微镜观察阳性细胞数,检测创伤后不同时间点脑损伤组织中VEGF表达情况。采集的标本采用干湿重法测定损伤脑组织的含水量。结果正常脑组织未检测到VEGF蛋白表达;脑创伤后3h脑组织中VEGF表达明显增加,72h达到高峰,7d后表达减少,与相同时间点脑组织含水量呈正相关。结论VEGF可能在颅脑创伤后继发脑水肿发生、发展中起重要作用。     

神经生长因子在重型颅脑损伤救治中的应用

目的 探讨神经生长因子（NGF）在重型颅脑损伤患者中的应用效果.方法 将70例重型颅脑损伤患者分为2组,对照组35例采用常规治疗,实验组35例在常规治疗的基础上加用NGF治疗.对2组患者格拉斯哥昏迷指数（GCS）评分及伤后6个月康复期生活质量（KPS）评估进行比较.结果 实验组的GCS评分从治疗第14天起明显好于对照组,伤后6个月随访KPS评分实验组明显优于对照组,未观察到与NGF有关的药物不良反应.结论 NGF能够促进重型颅脑损伤患者神经功能的恢复,改善预后.     

神经生长因子对颅脑损伤的保护作用

神经生长因子（NGF）具有促进神经元存活、生长发育及分化,保护受损神经元,诱导神经纤维定向生长和再生等多种效应。颅脑损伤后NGF与其受体结合,通过PI-3K—Akt、MEK—MAPK等途径调节某些基因的表达,诱导和增加某些蛋白表达（如生长相关蛋白、微管相关蛋白等）,从而保护受损的神经元,促进神经元修复、神经再生。本文就NGF的生物学效应、信号传导机制及促进颅脑损伤后神经再生的机制等研究进展进行综述。     

SD大鼠重型创伤性颅脑损伤后皮质Shankla蛋白的改变及意义

目的探讨Sprague—Dawley（SD）大鼠重型颅脑损伤后皮质组织中Shankla蛋白的表达改变及其意义。方法48只成年雄性SD大鼠,按随机数字表法,分为正常对照组、颅脑损伤后1h、6h、24h、48h及72h共6组,每组8只。采用免疫组化染色法和Western blot法行蛋白测定,RT—PCR法行mRNA测定。观察各颅脑损伤组及对照组大鼠Shankla蛋白及mRNA梯度灰度值,并进行免疫组化评分。结果与对照组比较,严重颅脑损伤后,Shankla蛋白和mRNA的表达量增加,从伤后1h持续到伤后72h（P〈0．05）,伤后24h表达量最高（P〈0.01）。结论在严重颅脑损伤后,Shankla出现1个表达高峰,在不同机制的影响下可能对脑损伤发生、发展起重要作用。     

亚低温通过调控PTEN表达保护损伤后大鼠脑组织

目的探讨颅脑损伤后亚低温保护机制及与PTEN的关系。方法采用Marmarou法制作SD大鼠颅脑损伤模型,设假手术组、常温损伤组(37℃,NT组)、亚低温损伤组(32℃~35℃,HT组)。检测亚低温治疗对大鼠颅脑损伤后6 h、24 h、72 h的保护作用及对损伤脑组织PTEN m RNA、蛋白表达的影响。结果损伤后脑组织PTEN m RNA与蛋白表达在伤后6 h已经开始增加,24 h达到高峰,72 h后仍高于假手术组。亚低温可降低颅脑损伤后各时间PTEN m RNA表达及伤后6 h、24 h PTEN蛋白浓度,但伤后72 h PTEN蛋白浓度,HT组和NT组无明显差异。结论颅脑损伤后神经元表达PTEN增多,亚低温通过下调神经元PTEN表达保护损伤后脑组织。     

rh—EPO对大鼠颅脑损伤模型脑红蛋白表达研究

目的观察重组人促红细胞生成素rh—EPO对大鼠脑损伤后皮层脑红蛋白NGB表达的影响,探讨其在脑损伤后的意义。方法78只大鼠随机分为3组：假手术组6只,单纯颅脑损伤组36只,rh—EPO干预组36只。单纯颅脑损伤组与rh—EPO干预组模型分别按照3h、6h、12h、24h、48h、72h 6个时间点随机分为6个亚组,每个亚组6只大鼠,通过免疫组化及图像分析方法,观察打击区周边皮层中脑红蛋白NGB的表达。结果单纯颅脑损伤组打击周边区NGB蛋白免疫反应阳性细胞表达较假手术组增多（P〈0．01）,在相应区域rh—EPO干预组明显高于前两组（P〈0．01）。结论rh—EPO可诱导增加大鼠脑损伤后脑红蛋白的表达。     

神经干细胞在脑损伤模型中的迁移、成活和神经生长因子表达

目的 探讨神经干细胞在脑损伤模型中的迁移、成活和神经生长因子(NGF)表达.方法 SD大鼠30只随机分为3组:正常对照组(n=5)、损伤组(n =10)和移植组(n=15).正常对照组不做任何处理,损伤组和移植组均制备脑损伤模型,且移植组大鼠从尾静脉注入外源性神经干细胞.并观察神经干细胞在大鼠脑内的迁移和存活情况,同时通过免疫组织化学染色检测各组大鼠脑内NGF阳性细胞数量.结果 神经干细胞移植2周后,其向脑损伤区域发生迁移,并在损伤区域聚集和存活;且移植组NGF阳性细胞数目较正常对照组和损伤组显著增多(p＜0.05).结论 外源性神经干细胞经尾静脉注射移植后能自动向脑损伤区域迁移、聚集并存活,并可促进受损脑内的NGF表达.     

幼龄和老龄大鼠液压颅脑伤后NGFmRNA表达差异

目的观察幼龄和老龄大鼠颅脑损伤后神经生长因子信使RNA(nerve growth factor mRNA ,NGFmRNA)表达差异,探讨老年动物中枢神经损伤后神经功能缺失较多的病理生理机制,以及改善老年颅脑损伤预后的方法.方法采用大鼠侧方液压打击颅脑损伤模型,应用原位杂交方法和计算机显微图象分析技术,比较幼龄(2～3个月)和老龄(15个月)大鼠脑损伤后12 h脑内 NGFmRNA 表达水平的差异,并用β2 受体激动剂克仑特罗(clenbuterol,CLE)作为干预手段,观察其对幼龄和老龄大鼠受损脑组织 NGFmRNA 表达的调节作用.结果液压打击伤后12 h,两组大鼠损伤脑组织NGFmRNA表达均有不同程度的增加,但是老龄鼠损伤侧大脑皮层NGFmRNA表达明显低于幼龄鼠( P <0.05);伤后立即应用CLE(0.5 mg/kg,腹腔注射)并不提高幼龄大鼠受伤脑组织NGFmRNA的表达,但可显著提高老龄鼠NGFmRNA的表达( P <0.01).结论脑损伤早期老龄鼠NGFmRNA表达较低提示老年动物受损脑组织修复能力减低,这为我们认识临床上老年颅脑损伤后神经功能缺失较多的原因提供了帮助;CLE能够增加老龄大鼠受损脑组织NGFmRNA表达并可能由此提高老年动物的神经修复能力.     

Leukodiapedesis and leukocyte migration in the leptomeninges and in the subarachnoid space

Summary Pleocytosis in cerebrospinal fluid and infiltration of the leptomeningeal tissue have been studied after injection of ferritin into the subarachnoid space (SAS) of cats.The most important source of granulocytes in the leptomeninges are the relatively large veins of the pia mater, which have very thin walls. Passing between the lining cells of the pia mater the granulocytes leave the connective tissue space of the pia mater and reach the SAS. Leukodiapedesis has also been observed in veins crossing the SAS. During this process, gaps between the lining cells of the perivascular leptomeningeal sheath may develop. There are two possible ways for the granulocytes to pass from the vascular pia mater to the avascular arachnoidea: either they migrate actively on the surface of the leptomeningeal trabeculae or they reach the arachnoidea passively by the circulation of the cerebrospinal fluid. Leukodiapedesis in the vessels of the dura mater occurs relatively seldom and would not be able to cause the occasionally massive infiltration of the arachnoidea.

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Zusammenfassung Nach subarachnoidaler Ferritin-Injektion wurde an Katzen die Entstehung der Liquorpleozytose und die Infiltration des leptomeningealen Gewebes beobachtet.Die weitlumigen, dünnwandigen venösen Gefäße der Pia mater stellen die wichtigsten Quellen der Granulozyten im leptomeningealen Bereich dar. Die Granulozyten verlassen den pialen Bindegewebsraum, indem sie zwischen den Lining-cells der Pia mater hindurch in den Subarachnoidalraum gelangen. Venen, die den Subarachnoidalraum durchqueren, weisen ebenfalls Leukodiapedesevorgänge auf. Zwischen den Lining-cells der perivasculären Scheide treten dabei offenbar Lücken auf. Den Granulozyten stehen zwei Möglichkeiten zur Verfügung, um die gefäßlose Arachnoidea von der vaskularisierten Pia mater aus zu erreichen: Entweder wandern sie aktiv über das leptomeningeale. Balkenwerk oder sie gelangen passiv mit der Liquorzirkulation dorthin. Hinweise auf Leukozytenaustritte aus den Duragefäßen sind vergleichsweise selten und würden die mitunter hochgradige Infiltration der Arachnoidea wohl nicht bewirken können.

     

Diurnal variation in the concentrations of catecholamines and indoleamines in the median eminence and in the intermediate and posterior lobes of the pituitary gland of the male rat

Diurnal changes in monoamine concentrations were studied in the median eminence and in the intermediate and posterior lobes of the pituitary gland of the male rat. The concentrations of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA) and dopamine (DA) were analyzed at 7 time points over a 24-h period. Diurnal variation was analyzed by analysis of variance (ANOVA) with time of day as a class variable as well as by 24 h and 12 h cosine curve fittings. There were marked time-dependent changes in the median eminence concentrations of 5-HT (ANOVA: P = 0.0085), 5-HIAA (P = 0.003) and NA (P = 0.0003). Cosine curves with 24-h periods fit the data points with peaks around 13.00 h. DA levels also varied with an apparent 24-h rhythm in the median eminence, but the changes did not reach the level of significance in the ANOVA. In the intermediate lobe of the pituitary gland, the concentrations of DA varied significantly during the course of the 24-h cycle (P = 0.0011) and were well-fitted to a 24-h cosine wave. The 5-HIAA levels also showed marked diurnal changes (P = 0.025) with an evident 12-h rhythm. In contrast, NA and 5-HT concentrations did not appear to vary during the 24-h cycle. In the posterior lobe of the pituitary gland. DA had a 24-h rhythm (P = 0.0005) similar to the intermediate lobe. NA and indoleamine levels did not show any significant variation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fighting in the aged male mouse increases the expression of TrkA and TrkB in the subventricular zone and in the hippocampus

In the present study, we investigate the effect of aggressive behavior and release of nerve growth factor (NGF) on brain progenitor cells. We found that the condition of subordination enhances the level of NGF in the subventricular zone and hippocampus whereas dominance elevates brain derived neurotrophic factor (BDNF). It was also found that mRNA-TrkA is over-expressed in the subventricular zone and hippocampus of dominant and subordinate mice, whereas mRNA-TrkB is increased in the subventricular zone of both dominants and subordinates and in the hippocampus of dominant mice. Fighting was also associated with increased presence of proliferating cells in the hippocampus stained with the nuclear marker bromodeoxyuridine (BrdU). Moreover, the brain of subordinate mice displayed tyrosine hydroxylase (TH) immunoreactivity in the wall of the periventricular region of the third ventricles and a marked neuropeptide Y (NPY) presence in the hippocampus co-expressed with BrdU. These results provide additional evidence that agonistic behavior in the aged mouse alters neurotrophin levels and increases brain progenitor cells number. The functional significance of these findings is discussed.     

Alzheimer's disease in the old and the young

This study concerns differences between Alzheimer's disease in the old and the young. Literature differentiating Alzheimer's disease from ‘senile dementia’ is reviewed. Two groups of mental hospital patients with Alzheimer brain changes at autopsy are compared. They comprised the 17 oldest and 17 youngest of the 56 ptients with definite Alzheimer changes in a series of 212 consecutive autopsies. The younger group had been first hospitalized at later ages than the older group, and were more likely to have been demented at admission. The older group had mostly been diagnosed as schizophrenic (mainly paranoid) on admission. Neuropathologically the younger group showed more severe Alzheimer changes of all kinds. The changes in the older group tended to be limited to the hippocampus, whereas in the younger group they showed extension into the frontal and occipital cortex and were also found in subcortical gray matter. Lipofuscin was more abundant in the older group, so that a discrepancy between very severe Alzheimer changes and less abundant lipofuscin characterizes the younger cases.