Sharifi Mohammad Davood, Karimi Narges, Karami Mohammad, Borhani Haghighi Afshin, Shabani Mohammad, Bayat Mahnaz
Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Physiology, The Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
Iran J Pharm Res. 2021 Fall;20(4):435-449. doi: 10.22037/IJPR.2020.113942.14576.
Chronic cerebral hypoperfusion (CCH) leads to vascular dementia with progressive hippocampal damage and cognitive impairments. In the present , we compared early and late Minocycline (MINO) treatment on cognitive function, long and short-term synaptic-plasticity following CCH. We used bilateral common carotid arteries occlusion model (2VO) for induction of hypoperfusion. Male Sprague-Dawley rats were divided into 5 following groups (each having 2 subgroups): 2VO + V (vehicle), 2VO+MINO-E (early treatment of MINO on days 0 to 3 after 2VO), 2VO+MINO-L (late-treatment on days 21 to 32 after 2VO), control, and sham. Passive-avoidance (PA) and radial arm maze (RAM) tests were used to investigate learning and memory. Long term and short term synaptic plasticity were assessed by field potential recording, the brains were removed after recording and preserved for histological study to count pyramidal cells in CA1 region.Cerebral hypoperfusion could impair memory performance, synaptic plasticity, and basal synaptic transmission (BST) along with hippocampal cell loss. Thus, we found a significant reduction in step-through latency (STL) of PA test with a higher number of working and reference errors in RAM in CCH rats. However, only late treatment with MINO improved memory performance, synaptic plasticity, hippocampal cell loss, and increased neurotransmitter pool (NP) in CCH rats, but early treatment could not produce long-lasting beneficial effects 32 days after 2VO. MINO may improve synaptic plasticity and memory performance in hypo-perfused rats directly and indirectly by increasing NP and/or suppressing inflammatory factors, respectively.
慢性脑灌注不足（CCH）会导致血管性痴呆，并伴有进行性海马损伤和认知障碍。在本研究中，我们比较了米诺环素（MINO）早期和晚期治疗对CCH后认知功能、长期和短期突触可塑性的影响。我们使用双侧颈总动脉闭塞模型（2VO）诱导灌注不足。将雄性Sprague-Dawley大鼠分为以下5组（每组有2个亚组）：2VO + V（溶剂对照组）、2VO+MINO-E（2VO后第0至3天早期给予MINO治疗）、2VO+MINO-L（2VO后第21至32天晚期给予MINO治疗）、对照组和假手术组。采用被动回避（PA）和放射状臂迷宫（RAM）试验来研究学习和记忆。通过场电位记录评估长期和短期突触可塑性，记录后取出大脑并保存用于组织学研究，以计数CA1区的锥体细胞。脑灌注不足会损害记忆表现、突触可塑性和基础突触传递（BST），同时伴有海马细胞丢失。因此，我们发现CCH大鼠的PA试验的穿通潜伏期（STL）显著缩短，RAM试验中的工作和参考错误数量更多。然而，只有晚期给予MINO可改善CCH大鼠的记忆表现、突触可塑性、海马细胞丢失，并增加神经递质池（NP），但早期治疗在2VO后32天不能产生持久的有益效果。MINO可能分别通过增加NP和/或抑制炎症因子直接和间接改善灌注不足大鼠的突触可塑性和记忆表现。
