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美金刚对大鼠闭合性颅脑损伤后脂质过氧化的影响。

The effects of memantine on lipid peroxidation following closed-head trauma in rats.

作者信息

Ozsüer Hakan, Görgülü Aşkin, Kiriş Talat, Cobanoğlu Sabahattin

机构信息

Department of Neurosurgery, Ataturk State Hospital, Izmir, Turkey.

出版信息

Neurosurg Rev. 2005 Apr;28(2):143-7. doi: 10.1007/s10143-004-0374-1. Epub 2005 Jan 26.

Abstract

Memantine is an uncompetitive N-methyl-D: -aspartate (NMDA) receptor antagonist. Unlike other NMDA antagonists, it has been used clinically for years for the treatment of Parkinson's disease, spasticity, and dementia without serious side effects. We aimed to investigate the therapeutic efficacy of memantine on a closed head trauma model. A total of 132 adult male Sprague-Dawley rats were randomly divided into four groups: sham-operated, control (closed head trauma), sham-vehicle (closed head trauma + saline), treatment (closed head trauma + memantine, 10 mg/kg, i.p.). A cranial impact was delivered to the skull, just in front of the coronal suture, over the left hemisphere, from the height of 7 cm. Saline or memantine were applied 15 min after trauma. Rats were euthanased 0.5, 1, 2, 6, 24, 48 h after trauma. Brain tissue samples were taken 5 mm away from the left frontal pole and also from the corresponding point of the contralateral hemispheres. Malondialdehyde activity (MDA) was considered to reflect the degree of lipid peroxidation. The MDA levels continued to increase for the first 2 h after the injury, then started to decrease gradually. Memantine treatment significantly reduced lipid peroxidation levels in the treatment group compared with other groups (P<0.01). The findings of the present study indicate that memantine provides beneficial effects after closed head trauma in rats.

摘要

美金刚是一种非竞争性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂。与其他NMDA拮抗剂不同,它已在临床上使用多年,用于治疗帕金森病、痉挛和痴呆,且无严重副作用。我们旨在研究美金刚对闭合性颅脑损伤模型的治疗效果。总共132只成年雄性Sprague-Dawley大鼠被随机分为四组:假手术组、对照组(闭合性颅脑损伤)、假载体组(闭合性颅脑损伤+生理盐水)、治疗组(闭合性颅脑损伤+美金刚,10mg/kg,腹腔注射)。从7cm高度将颅脑撞击施加于颅骨,位于冠状缝前方、左半球上方。创伤后15分钟给予生理盐水或美金刚。在创伤后0.5、1、2、6、24、48小时对大鼠实施安乐死。从左额极5mm处以及对侧半球的相应点采集脑组织样本。丙二醛活性(MDA)被认为可反映脂质过氧化程度。损伤后的前2小时MDA水平持续升高,随后开始逐渐下降。与其他组相比,美金刚治疗显著降低了治疗组的脂质过氧化水平(P<0.01)。本研究结果表明,美金刚对大鼠闭合性颅脑损伤具有有益作用。

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