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加兰他敏可改善脊髓损伤大鼠模型的功能恢复并减小损伤体积。

Galantamine improves functional recovery and reduces lesion size in a rat model of spinal cord injury.

机构信息

Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Av. Ipiranga, 2752, Universidade Federal do Rio Grande do Sul, 90610-000 Porto Alegre, Brazil; UNISINOS, São Leopoldo, Brazil.

Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Av. Ipiranga, 2752, Universidade Federal do Rio Grande do Sul, 90610-000 Porto Alegre, Brazil.

出版信息

Brain Res. 2019 Dec 1;1724:146424. doi: 10.1016/j.brainres.2019.146424. Epub 2019 Aug 28.

Abstract

Spinal cord injury (SCI) is a medical condition that currently lacks effective treatment. Galantamine is a reversible, competitive acetylcholinesterase inhibitor, used to treat patients with Alzheimeŕs disease. It has been demonstrated that galantamine increases cerebral neurogenesis and has a neuroprotective effect by binding to nicotinic receptors and has an anti-inflammatory effect due to its allosteric binding to the α7nAChR. In the present study, the effects of galantamine on functional recovery and histological outcome in a rat contusion model of SCI were analyzed. Male Wistar rats were submitted to SCI using a NYU/MASCIS impactor. The animals from the galantamine group were treated with 5 mg/kg galantamine intraperitoneally for 5 days. The Basso, Beattie and Bresnahan scale (BBB) was used to evaluate locomotor activity. The expression of beta3-tubulin, NFM, GFAP, O4, CD68 and CD3 was analyzed by flow cytometry. Rats that received galantamine had significantly higher BBB scores in comparison with the control lesion group. Galantamine treatment increased the percentage of NFM positive cells at 6 weeks post-injury and reduced the size of the lesion. The results indicate that galantamine increased tissue survival and accelerated hind limb motor function recovery. This is the first study that has shown the possibility of therapeutic use of galantamine in a model of acute spinal cord injury.

摘要

脊髓损伤 (SCI) 是一种目前缺乏有效治疗方法的医学病症。加兰他敏是一种可逆的、竞争性乙酰胆碱酯酶抑制剂,用于治疗阿尔茨海默病患者。已经证明加兰他敏通过与烟碱型乙酰胆碱受体结合增加大脑神经发生并具有神经保护作用,并且由于其变构结合到α7nAChR 而具有抗炎作用。在本研究中,分析了加兰他敏对 SCI 大鼠挫伤模型中功能恢复和组织学结果的影响。雄性 Wistar 大鼠使用 NYU/MASCIS 撞击器进行 SCI。加兰他敏组的动物接受 5mg/kg 加兰他敏腹膜内注射 5 天。Basso、Beattie 和 Bresnahan 量表 (BBB) 用于评估运动活动。通过流式细胞术分析 beta3-微管蛋白、NFM、GFAP、O4、CD68 和 CD3 的表达。与对照损伤组相比,接受加兰他敏的大鼠 BBB 评分显着更高。加兰他敏治疗可增加损伤后 6 周时 NFM 阳性细胞的百分比并减少损伤的大小。结果表明,加兰他敏增加了组织存活并加速了后肢运动功能的恢复。这是首次表明在急性脊髓损伤模型中加兰他敏具有治疗用途的可能性的研究。

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