Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut P.O. Box 6573/14, Lebanon.
Rammal Hassan Rammal Research Laboratory, Physiotoxicity (PhyTox), Faculty of Sciences, Lebanese University, Beirut P.O. Box 6573/14, Lebanon.
Molecules. 2021 Feb 5;26(4):839. doi: 10.3390/molecules26040839.
Chronic cerebral ischemia with a notable long-term cessation of blood supply to the brain tissues leads to sensorimotor defects and short- and long-term memory problems. Neuroprotective agents are used in an attempt to save ischemic neurons from necrosis and apoptosis, such as the antioxidant agent . Numerous studies have demonstrated the involvement of the renin-angiotensin system in the initiation and progression of cardiovascular and neurodegenerative diseases. Candesartan is a drug that acts as an angiotensin II receptor 1 blocker. We established a rat model exhibiting sensorimotor and cognitive impairments due to chronic cerebral ischemia induced by the ligation of the right common carotid artery. Wistar male rats were randomly divided into five groups: Sham group, Untreated Ligated group, Ischemic group treated with (500 mg/kg), Ischemic group treated with Candesartan (0.5 mg/kg), and Ischemic group treated with a combination of and Candesartan. To evaluate the sensorimotor disorders, we performed the beam balance test, the beam walking test, and the modified sticky test. Moreover, the object recognition test and the Morris water maze test were performed to assess the memory disorders of the rats. The infarct rat brain regions were subsequently stained using the triphenyltetrazolium chloride staining technique. The rats in the Sham group had normal sensorimotor and cognitive functions without the appearance of microscopic ischemic brain lesions. In parallel, the untreated Ischemic group showed severe impaired neurological functions with the presence of considerable brain infarctions. The treatment of the Ischemic group with a combination of both and Candesartan was more efficient in improving the sensorimotor and cognitive deficits ( < 0.001) than the treatment with or Candesartan alone ( < 0.05), by the comparison to the non-treated Ischemic group. Our study shows that the combination of and Candesartan could decrease ischemic brain injury and improve neurological outcomes.
慢性脑缺血导致脑组织长期停止供血，可导致感觉运动缺陷以及短期和长期记忆问题。神经保护剂被用于试图挽救缺血神经元免于坏死和凋亡，如抗氧化剂。许多研究表明，肾素-血管紧张素系统参与了心血管和神经退行性疾病的发生和发展。坎地沙坦是一种作用于血管紧张素 II 受体 1 的拮抗剂。我们建立了一个大鼠模型，通过结扎右侧颈总动脉导致慢性脑缺血，从而表现出感觉运动和认知障碍。雄性 Wistar 大鼠随机分为五组：假手术组、未治疗结扎组、缺血组用 （500mg/kg）治疗、缺血组用坎地沙坦（0.5mg/kg）治疗、缺血组用 与坎地沙坦联合治疗。为了评估感觉运动障碍，我们进行了平衡木试验、走棒试验和改良粘胶试验。此外，还进行了物体识别试验和 Morris 水迷宫试验来评估大鼠的记忆障碍。随后使用氯化三苯基四氮唑染色技术对梗塞大鼠脑区进行染色。假手术组大鼠具有正常的感觉运动和认知功能，没有出现显微镜下的缺血性脑损伤。与此同时，未经治疗的缺血组大鼠表现出严重的神经功能障碍，并且存在大量脑梗死。与未治疗的缺血组相比，缺血组联合使用 和坎地沙坦治疗在改善感觉运动和认知缺陷方面更为有效（<0.001），优于单独使用 或坎地沙坦治疗（<0.05）。我们的研究表明， 和坎地沙坦的联合使用可以减少缺血性脑损伤并改善神经功能结局。
