Department of Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, 154, Anshan Road, Tianjin, 300052, China.
The Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA.
J Mol Neurosci. 2017 Oct;63(2):223-232. doi: 10.1007/s12031-017-0974-1. Epub 2017 Sep 17.
Cerebral hypoperfusion is an important factor in the pathogenesis of cerebrovascular diseases and neurodegenerative disorders. We investigated the effects of memantine and rosuvastatin on both neovascularization and synaptic function in a rat model of chronic cerebral hypoperfusion, which was established by the bilateral common carotid occlusion (2VO) method. We tested learning and memory ability, synaptic function, circulating endothelial progenitor cell (EPC) number, expression of neurotrophic factors, and markers of neovasculogenesis and cell proliferation after memantine and/or rosuvastatin treatment. Rats treated with memantine and/or rosuvastatin showed significant improvement in Morris water maze task and long-term potentiation (LTP) in the hippocampus, compared with untreated 2VO model rats. Circulating EPCs, expression of brain-derived neurotrophic factor, and vascular endothelial growth factor, markers of microvessel density were increased by each of the three interventions. Rosuvastatin also increased cell proliferation in the hippocampus. Combined treatment with memantine and rosuvastatin showed greater effect on enhancement of LTP and expression of neurotrophic factors than either single medication treatment alone. Both memantine and rosuvastatin improved learning and memory, enhanced neovascularization and synaptic function, and upregulated neurotrophic factors in a rat model of chronic cerebral hypoperfusion.
脑灌注不足是脑血管病和神经退行性疾病发病机制中的一个重要因素。我们通过双侧颈总动脉闭塞（2VO）方法建立慢性脑灌注不足大鼠模型，研究了美金刚和瑞舒伐他汀对血管新生和突触功能的影响。我们检测了学习和记忆能力、突触功能、循环内皮祖细胞（EPC）数量、神经营养因子表达以及新生血管生成和细胞增殖的标志物，在给予美金刚和/或瑞舒伐他汀治疗后。与未治疗的 2VO 模型大鼠相比，接受美金刚和/或瑞舒伐他汀治疗的大鼠在 Morris 水迷宫任务和海马长时程增强（LTP）中表现出显著改善。三种干预措施均增加了循环 EPCs、脑源性神经营养因子和血管内皮生长因子的表达，微血管密度的标志物增加。瑞舒伐他汀还增加了海马的细胞增殖。美金刚和瑞舒伐他汀联合治疗在增强 LTP 和神经营养因子表达方面的效果优于单独使用任何一种药物。美金刚和瑞舒伐他汀均可改善慢性脑灌注不足大鼠的学习和记忆能力，增强血管新生和突触功能，并上调神经营养因子。
