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Abstract：
Purpose The purpose of this study was to investigate the effect of dexmedetomidine (DEX) on hypotension-induced neuronal damage in a chronic cerebral hypoperfusion (CCH) model of rats, an established model of cerebral white matter lesions (WML) in humans, which is prevalent in the elderly and closely related to cognitive decline. Methods The CCH model rats were randomly assigned to one of four groups: normotension + no DEX (NN) group (n = 6), normotension + DEX (ND) group (n = 6), hypotension + no DEX (HN) group (n = 6), or hypotension + DEX (HD) group (n = 6). Under isoflurane anesthesia, mean arterial blood pressure was maintained at or above 80 mmHg (normotension) or below 60 mmHg (hypotension) for a duration of two hours. The DEX groups received 50 μg of DEX intraperitoneally. Two weeks later, the Y-maze test and, after preparing brain slices, immunohistochemical staining were performed using antibodies against neuronal nuclei (NeuN), microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adapter molecule 1 (Iba1). Results Behavioral observations showed no significant differences among the groups. Significant reductions of both NeuN-positive cells and the MAP2-positive area were found in the hippocampal CA1 in the HN group compared with NN and ND groups, but not in the HD group. GFAP and Iba-1-positive areas were significantly increased in the HN group, but not in the HD group. Conclusion DEX significantly ameliorated hypotension-induced neuronal damage and both astroglial and microglial activation in the CA1 region of CCH rats.
摘要：
目的探讨右美托咪定(DEX)对低血压诱导的大鼠慢性脑低灌注(CCH)模型神经元损伤的影响。建立了人类脑白质病变（WML）模型，这在老年人中普遍存在，与认知能力下降密切相关。方法将CCH模型大鼠随机分为四组:正常血压+无DEX(NN)组(n=6),常压+DEX(ND)组(n=6)，低血压+无DEX(HN)组(n=6),或低血压+DEX(HD)组(n=6)。在异氟烷麻醉下,平均动脉血压维持在80mmHg或以上(常压)或60mmHg以下(低血压)两小时.DEX组腹膜内接受50μgDEX。两周后,Y迷宫测试，在准备脑切片后，免疫组织化学染色使用抗神经元核抗体（NeuN），微管相关蛋白2（MAP2），胶质纤维酸性蛋白（GFAP），和电离的钙结合接头分子1(Ibal)。结果行为观察显示各组之间没有显着差异。与NN和ND组相比，HN组海马CA1区NeuN阳性细胞和MAP2阳性面积均显著减少，但不是HD组。GFAP和Iba-1阳性区域在HN组中显著增加,但不是HD组。结论DEX能显著改善低血压诱导的CCH大鼠CA1区神经元损伤及星形胶质细胞和小胶质细胞活化。
