Jiao Chun-Xiang, Zhou Heng, Yang Chun-Xian, Ma Chen, Yang Yue-Xiong, Mao Rong-Rong, Xu Lin, Zhou Qi-Xin
Laboratory of Learning and Memory, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, CAS, Kunming.
Kunming College of Life Sciences, University of Chinese Academy of Sciences.
Neuropsychiatr Dis Treat. 2017 Apr 26;13:1181-1192. doi: 10.2147/NDT.S127094. eCollection 2017.
With respect to the high burden of ischemic stroke and the absence of pharmacological treatment for promoting rehabilitation, promising candidates with specific effects on long-term functional recovery are highly desired. Candidates need reasonable experimental paradigms to evaluate the long-term functional outcome focused on ischemia-induced sensorimotor and memory deficits. "Danshen", a traditional Chinese herb, has long been used to treat coronary and cerebral vascular diseases as well as dementia. Salvianolic acid A (SAA), one of the major active ingredients of Danshen, was demonstrated to be effective in protecting against cerebral ischemic injury. Here, employing an experimental stroke model induced by photothrombosis in the unilateral frontal cortex of rats, we investigated whether SAA has long-term protective effects on ischemia-induced sensorimotor and memory deficits in our behavioral tests. The results indicated that a single SAA treatment improved the cortical ischemia-induced sensorimotor deficits during 15 days' cylinder test period, and alleviated ischemia-induced sustained spatial memory impairments during the 2 months' dependent Morris Water Maze (MWM) tests. In addition, either ischemic injury or SAA treatment did not show any changes compared with sham group in other behavioral tests including rotarod tests, swimming speed in MWM tests, open field tests, elevated plus maze tests, treadmill tests and forced swimming tests. The results reveal that the cognitive deficits are not the results of animal's anxiety or confounding motor impairments. Overall, the present paradigm appears suitable for the preclinical evaluation of the long-term effects of pharmacological treatments on ischemic stroke. Meanwhile, SAA might have therapeutic potential for the treatment of memory deficits associated with ischemic stroke.
鉴于缺血性中风的高负担以及缺乏促进康复的药物治疗，人们迫切需要对长期功能恢复具有特定作用的有前景的候选药物。候选药物需要合理的实验范式来评估针对缺血性诱导的感觉运动和记忆缺陷的长期功能结果。丹参，一种传统的中草药，长期以来一直用于治疗冠状动脉和脑血管疾病以及痴呆症。丹酚酸A（SAA）是丹参的主要活性成分之一，已被证明对预防脑缺血损伤有效。在此，我们采用光血栓形成诱导大鼠单侧额叶皮质实验性中风模型，在行为测试中研究SAA是否对缺血诱导的感觉运动和记忆缺陷具有长期保护作用。结果表明，单次SAA治疗在为期15天的圆筒测试期间改善了皮质缺血诱导的感觉运动缺陷，并在为期2个月的依赖型莫里斯水迷宫（MWM）测试中减轻了缺血诱导的持续空间记忆损伤。此外，在其他行为测试中，包括转棒试验、MWM测试中的游泳速度、旷场试验、高架十字迷宫试验、跑步机试验和强迫游泳试验，与假手术组相比，缺血损伤或SAA治疗均未显示出任何变化。结果表明，认知缺陷不是动物焦虑或混杂运动障碍的结果。总体而言，目前的范式似乎适用于对缺血性中风药物治疗长期效果的临床前评估。同时，SAA可能对治疗与缺血性中风相关的记忆缺陷具有治疗潜力。
