Damodaran Thenmoly, Hassan Zurina, Navaratnam Visweswaran, Muzaimi Mustapha, Ng Gandi, Müller Christian P, Liao Ping, Dringenberg Hans C
Centre for Drug Research, Universiti Sains Malaysia, 11800 Penang, Malaysia.
Centre for Drug Research, Universiti Sains Malaysia, 11800 Penang, Malaysia; Centre for Neuroscience Services and Research, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia.
Behav Brain Res. 2014 Dec 15;275:252-8. doi: 10.1016/j.bbr.2014.09.014. Epub 2014 Sep 17.
Cerebral ischemia is one of the leading causes of death and long-term disability in aging populations, due to the frequent occurrence of irreversible brain damage and subsequent loss of neuronal function which lead to cognitive impairment and some motor dysfunction. In the present study, the real time course of motor and cognitive functions were evaluated following the chronic cerebral ischemia induced by permanent, bilateral occlusion of the common carotid arteries (PBOCCA). Male Sprague Dawley rats (200-300g) were subjected to PBOCCA or sham-operated surgery and tested 1, 2, 3 and 4 weeks following the ischemic insult. The results showed that PBOCCA significantly reduced step-through latency in a passive avoidance task at all time points when compared to the sham-operated group. PBOCCA rats also showed significant increase in escape latencies during training in the Morris water maze, as well as a reduction of the percentage of times spend in target quadrant of the maze at all time points following the occlusion. Importantly, there were no significant changes in locomotor activity between PBOCCA and sham-operated groups. The BDNF expression in the hippocampus was 29.3±3.1% and 40.1±2.6% on day 14 and 28 post PBOCCA, respectively compared to sham-operated group. Present data suggest that the PBOCCA procedure effectively induces behavioral, cognitive symptoms associated with cerebral ischemia and, consequently, provides a valuable model to study ischemia and related neurodegenerative disorder such as Alzheimer's disease and vascular dementia.
脑缺血是老年人群死亡和长期残疾的主要原因之一,这是由于不可逆性脑损伤频繁发生以及随后神经元功能丧失,进而导致认知障碍和一些运动功能障碍。在本研究中,对永久性双侧颈总动脉闭塞(PBOCCA)诱导的慢性脑缺血后运动和认知功能的实时进程进行了评估。将雄性Sprague Dawley大鼠(200 - 300g)进行PBOCCA手术或假手术,并在缺血损伤后1、2、3和4周进行测试。结果显示,与假手术组相比,PBOCCA在所有时间点均显著缩短了被动回避任务中的穿通潜伏期。PBOCCA大鼠在Morris水迷宫训练期间的逃避潜伏期也显著增加,并且在闭塞后的所有时间点,其在迷宫目标象限停留时间的百分比均降低。重要的是,PBOCCA组和假手术组之间的运动活动没有显著变化。与假手术组相比,PBOCCA后第14天和第28天海马中脑源性神经营养因子(BDNF)的表达分别为29.3±3.1%和40.1±2.6%。目前的数据表明,PBOCCA程序有效地诱导了与脑缺血相关的行为和认知症状,因此为研究缺血及相关神经退行性疾病(如阿尔茨海默病和血管性痴呆)提供了一个有价值的模型。