In vitro synaptotrophic effects of Cerebrolysin in NT2N cells

Recent studies have shown that Cerebrolysin can enhance synaptic function and ameliorate synapto-dendritic alterations in animal models of neurodegeneration, suggesting a synaptotrophic effect. We hypothesize that Cerebrolysin might exert this effect, in part, by regulating the expression of amyloid precursor protein (APP). We studied the patterns of expression of synaptic proteins during differentiation of human teratocarcinoma cell line NTera 2 (NT2) in the presence or absence of Cerebrolysin. This study showed that the terminally differentiated neurons (NT2N) expressed a wide variety of synaptic markers and that expression of these synaptic-associated proteins coincided with the shift in expression from APP770/751 to APP695. Furthermore, APP immunoreactivity was colocalized with synaptophysin-immunoreactive neuritic varicosities in NT2N neurites, and Cerebrolysin treatment of NT2N cells resulted in an augmented and earlier expression of synaptic-associated proteins. This increased synaptic protein expression coincided with an increase in APP695 over APP770/751. These results support the possibility that synaptotrophic effects of Cerebrolysin might be mediated via regulation of APP expression. Received: 17 August 1998 / Accepted: 29 October 1998     

脑活素治疗血管性痴呆对照研究

目的;验证脑活素治疗血管性痴呆的疗效。方法：为多中心双盲随机平行对照研究。脑活素与安慰剂的剂量均为１００ｍｌ的注射剂,安慰剂为生理盐水,研究药含３０毫升脑活素。治疗方法静脉滴注,共４周２０次。结果;共入组并完成观察１４７例ＶＤ病人,脑活素组和安慰剂对照组分别为７５例和７２例。治疗４周后,脑活素组简明智力检查量表平均总分比治疗前提高了２．７分,两组具有显著性差异。     

脑蛋白水解物对鼠缺血半暗带神经元Na+-K+-ATP酶活性影响

目的探讨脑蛋白水解物对大鼠急性脑缺血再灌注损伤后缺血半暗带神经元Na~+-K~+-ATP酶活性的影响。方法选取270只雄性Wistar大鼠随机分为假手术组、模型组、干预组,三组大鼠根据缺血再灌注不同时间又随机分为缺血2 h再灌注6 h、24 h、48 h、72 h、7 d五个亚组,每个亚组18只大鼠。采用线栓法制备大鼠缺血2 h再灌注模型,仅干预组采用药物进行干预。分别于再灌注6 h、24 h、48 h、72 h、7 d后观察大鼠神经症状评分,相应时间断头取脑,测定缺血半暗带脑组织Na~+-K~+-ATP酶活性、脑组织含水量、脑梗死范围的变化。结果模型组大鼠缺血半暗带神经元Na~+-K~+-ATP酶活性于6 h开始下降,48 h达最小值,72 h稍有回升,7 d趋于稳定;干预组大鼠缺血2 h后再灌注24 h、48 h、72 h各时间点Na~+-K~+-ATP酶活性与模型组大鼠相应时间点比较差异有统计学意义(P0.05)。结论脑蛋白水解物可保护大鼠急性脑缺血再灌注损伤后缺血半暗带神经元,该作用可能与提高缺血半暗带神经元Na~+-K~+-ATP酶活性有关。     

Cerebrolysin and morphine decrease glutathione and 5-hydroxyindole acetic acid levels in fasted rat brain

Purpose

The aim was to evaluate if morphine sulphate combined with cerebrolysin enhances the risk of oxidative damage in the presence of moderate hypoglycaemia.

Methods

Wistar rats under starvation for 48 h received a single dose of 215 mg/kg cerebrolysin or 4 mg/kg morphine sulphate. Glutathione (GSH) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in brain tissue, as well as lipid peroxidation, Na⁺–K⁺ ATPase and total ATPase enzymatic activities, by fluorescence and spectrophotometric methods.

Results

GSH and 5-HIAA levels decreased significantly (p < 0.05) in animals which received cerebrolysin and morphine alone or combined. TBARS levels increased in all groups, but the values were statistically significant only in those animals that received cerebrolysin combined with morphine (p < 0.05). Na⁺–K⁺ ATPase and total ATPase activities decreased significantly in rats treated only with morphine, but the cerebrolysin and morphine groups showed a significant increase in these enzymatic activities.

Conclusions

Results suggest that cerebrolysin as well as morphine induced changes in cellular regulation and biochemical responses to oxidative stress induced by moderate hypoglycaemia in brain.     

灯盏花素对小鼠学习记忆能力的影响

本文应用峡谷种模型观察了灯盏花素对小鼠学习，记忆能力的影响。结果表明；灯盏花素能明显改善东莨苦所致的小鼠学习记忆获得障碍，明显改善乙醇所致的记忆再现障碍，并使学习能力明显加强，与已用于治疗学习记忆障碍的药物－脑复素比较，作用相近或稍强。     

Anterior thalamic nuclei lesions and recovery of function: Relevance to cognitive thalamus

Injury to the anterior thalamic nuclei (ATN) and their neural connections is the most consistent neuropathology associated with diencephalic amnesia. ATN lesions in rats produce memory impairments that support a key role for this region within an extended hippocampal system of complex overlapping neural connections. Environmental enrichment is a therapeutic tool that produces substantial, although incomplete, recovery of memory function after ATN lesions, even after the lesion-induced deficit has become established. Similarly, the neurotrophic agent cerebrolysin, also counters the negative effects of ATN lesions. ATN lesions substantially reduce c-Fos expression and spine density in the retrosplenial cortex, and reduce spine density on CA1 neurons; only the latter is reversed by enrichment. We discuss the implications of this evidence for the cognitive thalamus, with a proposal that there are genuine interactions among different but allied thalamo-cortical systems that go beyond a simple summation of their separate effects.     

施普善对慢性低O2高CO2大鼠空间学习记忆损害的干预作用

目的：观察慢性低O2高CO2大鼠的学习记忆改变及施普善的干预作用。方法：通过八臂迷宫训练筛选的SD大鼠,随机分为对照组（n=8）、慢性低O2高CO2组（n=8）、慢性低O2高CO2＋施普善1mL／kg组（简称施普善1mL／kg组,n=-8）和慢性低O2高CO2＋施普善2．5mL／kg组（简称施普善2．5mL／kg组,n=8）。将慢性低O2高CO2组及施普善干预组（1mL／kg、2．5mL／kg）大鼠放置于低O2高CO2密闭氧舱饲养4周,每天8h,每周6d。施普善干预组每天进氧舱前按既定剂量腹腔注射,慢性低O2高CO2组注射生理盐水。以八臂迷宫和Morris水迷宫实验测定其空间学习记忆功能。结果：与正常对照组相比,慢性低O2高CO2组的工作记忆错误（WME）为（1．31±1．19）次,明显高于正常对照组（0．56±0．50）次（P〈0．05）,而施普善1mL／kg组和2．5mL／kg干预组WME均较慢性低O2高CO2模型组明显减少（P〈0．05）。Mortis水迷宫,定位航行测试显示,慢性低O2高CO2模型组第3、第4、第5天的逃避潜伏期均较对照组明显延长（P〈0．05）,施普善1mL／kg组与慢性低O2高CO2组相比,第4、第5天的逃避潜伏期明显缩短（P〈0．05）,施普善2．5mL／kg组与慢性低O2高CO2组相比,第3、第4、第5天的逃避潜伏期明显缩短（P〈0．05）。空间搜索测试结果显示,慢性低O2高CO2组的平台穿越次数明显少于正常对照组及施普善干预组。结论：慢性低O2高CO2大鼠空间学习记忆受损,短时记忆受损明显,施普善干预可以改善慢性低O2高cO。大鼠模型的空间学习记忆能力。     

脑活素治疗新生儿缺血缺氧性脑病对血钙、镁的影响

目的:探讨脑活素治疗新生儿缺氧缺血性脑病后对血钙、镁的影响。方法:中、重度新生儿缺氧缺血性脑病组共70例,应用脑活素治疗前、后分别抽取静脉血,检测血钙、镁值,观察血钙血镁的变化。结果:脑活素治疗新生儿缺氧缺血性脑病后血钙、镁浓度显著高于治疗前(P分别<0.05)。结论:脑活素可通过提高血钙、镁浓度以改善缺氧缺血性脑病损伤。     

复方丹参注射液对小鼠的学习记忆能力的影响

目的与方法　采用跳台法测定复方丹参液对小鼠学习记忆能力的作用。结果　复方丹参液能明显改善东莨菪碱所致的小鼠学习记忆获得障碍 (与模型组比较 ,P <0 .0 1) ,且较脑复素更有效。结论　复方丹参液对改善学习记忆有一定作用     

甲泼尼松龙联合施普善治疗急性视神经炎疗效观察

目的:甲泼尼松龙大剂量冲击疗法和施普善辅助治疗对严重急性视神经炎的疗效观察。方法:28例(42眼)失明的急性视神经炎,采用静脉滴入大剂量甲泼尼松龙1.0g冲击疗法,配合施普善20mL,ATP40mg静脉滴注。结果:28例(42眼)视力均有不同程度的提高,总有效率为93%。部分患者追踪随访0.5a视力能有提高和巩固。结论:甲泼尼松龙冲击疗法治疗时间短,疗效高,作用迅速,副作用少,无复发。配合施普善治疗疗效更显著。