Zhang Yanlu, Chopp Michael, Meng Yuling, Zhang Zheng Gang, Doppler Edith, Winter Stefan, Schallert Timothy, Mahmood Asim, Xiong Ye
Departments of 1 Neurosurgery and.
J Neurosurg. 2015 Apr;122(4):843-55. doi: 10.3171/2014.11.JNS14271. Epub 2015 Jan 23.
Long-term memory deficits occur after mild traumatic brain injuries (mTBIs), and effective treatment modalities are currently unavailable. Cerebrolysin, a peptide preparation mimicking the action of neurotrophic factors, has beneficial effects on neurodegenerative diseases and brain injuries. The present study investigated the long-term effects of Cerebrolysin treatment on cognitive function in rats after mTBI.
Rats subjected to closed-head mTBI were treated with saline (n = 11) or Cerebrolysin (2.5 ml/kg, n = 11) starting 24 hours after injury and then daily for 28 days. Sham animals underwent surgery without injury (n = 8). To evaluate cognitive function, the modified Morris water maze (MWM) test and a social odor-based novelty recognition task were performed after mTBI. All rats were killed on Day 90 after mTBI, and brain sections were immunostained for histological analyses of amyloid precursor protein (APP), astrogliosis, neuroblasts, and neurogenesis.
Mild TBI caused long-lasting cognitive memory deficits in the MWM and social odor recognition tests up to 90 days after injury. Compared with saline treatment, Cerebrolysin treatment significantly improved both long-term spatial learning and memory in the MWM test and nonspatial recognition memory in the social odor recognition task up to 90 days after mTBI (p < 0.05). Cerebrolysin significantly increased the number of neuroblasts and promoted neurogenesis in the dentate gyrus, and it reduced APP levels and astrogliosis in the corpus callosum, cortex, dentate gyrus, CA1, and CA3 regions (p < 0.05).
These results indicate that Cerebrolysin treatment of mTBI improves long-term cognitive function, and this improvement may be partially related to decreased brain APP accumulation and astrogliosis as well as increased neuroblasts and neurogenesis.
轻度创伤性脑损伤（mTBI）后会出现长期记忆缺陷，而目前尚无有效的治疗方法。脑蛋白水解物是一种模拟神经营养因子作用的肽制剂，对神经退行性疾病和脑损伤具有有益作用。本研究调查了脑蛋白水解物治疗对mTBI大鼠认知功能的长期影响。
闭合性颅脑mTBI大鼠在受伤后24小时开始用生理盐水（n = 11）或脑蛋白水解物（2.5 ml/kg，n = 11）治疗，然后每天治疗，持续28天。假手术动物接受无损伤手术（n = 8）。为评估认知功能，在mTBI后进行改良的莫里斯水迷宫（MWM）测试和基于社交气味的新奇识别任务。所有大鼠在mTBI后第90天处死，取脑切片进行免疫染色，用于淀粉样前体蛋白（APP）、星形胶质细胞增生、神经母细胞和神经发生的组织学分析。
轻度TBI在损伤后长达90天的MWM和社交气味识别测试中导致持久的认知记忆缺陷。与生理盐水治疗相比，脑蛋白水解物治疗在mTBI后长达90天的时间里，显著改善了MWM测试中的长期空间学习和记忆以及社交气味识别任务中的非空间识别记忆（p < 0.05）。脑蛋白水解物显著增加了齿状回中神经母细胞的数量并促进了神经发生，并且降低了胼胝体、皮质、齿状回、CA1和CA3区域的APP水平和星形胶质细胞增生（p < 0.05）。
这些结果表明，脑蛋白水解物治疗mTBI可改善长期认知功能，这种改善可能部分与脑内APP积累减少、星形胶质细胞增生减少以及神经母细胞和神经发生增加有关。
