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生育酚和强力霉素对大鼠创伤性脑损伤所致认知/运动功能障碍的药理潜力。

Pharmacological potential of tocopherol and doxycycline against traumatic brain injury-induced cognitive/motor impairment in rats.

作者信息

Rana Arti, Singh Shamsher, Deshmukh Rahul, Kumar Anoop

机构信息

Department of Neuropharmacology, ISF College of Pharmacy , Moga, Punjab, India.

Department of Pharmaceutical Sciences & Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU) , Bathinda, Punjab, India.

出版信息

Brain Inj. 2020 Jul 2;34(8):1039-1050. doi: 10.1080/02699052.2020.1772508. Epub 2020 Jun 4.

DOI:10.1080/02699052.2020.1772508
PMID:32493074
Abstract

Primary Objective The primary objective of this study was to explore the pharmacological potential of tocopherol and doxycycline against traumatic brain injury-induced cognitive/motor impairment in rats. Research Design Weight drop model of traumatic brain injury. Methods and Procedures After TBI, the animals were treated with doxycycline (50 and 100 mg/kg; p.o), tocopherol (5 and 10 mg/kg; p.o) alone and in combination as doxycycline and tocopherol (50 and 10 mg/kg; p.o) from 1st day to 28th day. The behavioral parameters were performed on a weekly basis from 1st day to 28th day. On 29th day, animals were sacrificed and striatum and cortex were homogenized for the estimation of biochemical (LPO, nitrite, and GSH), neuroinflammatory (IL-6, IL-1β, and TNF-α), and neurotransmitters (dopamine, norepinephrine, serotonin, GABA, and glutamate) analysis. Main Outcomes and Results Induction of TBI had significantly reduced locomotor activity, recognition memory, increased neuroinflammatory markers, and imbalance neurotransmitter levels. The treatment with doxycycline and tocopherol alone and in combination significantly attenuated locomotor activity, memory recognition, reduced neuroinflammation, preserved oxidative balance, and restored the level of neurotransmitters. Conclusions The neuroprotective effect of doxycycline and tocopherol might be due to its anti-inflammatory and free radical scavenging mechanisms. Abbreviations TBI: Traumatic brain injury; Doxy: Doxycycline; Toco: Tocopherol; LPO: Lipid peroxidation; MDA: Malondialdehyde; TNF-α: Tumor necrosis factor-alpha; IL-1b: Interleukin-1 beta; GSH: Glutathione; GABA: gamma-Aminobutyric acid.

摘要

主要目标 本研究的主要目标是探究生育酚和强力霉素对大鼠创伤性脑损伤所致认知/运动功能障碍的药理潜力。研究设计 创伤性脑损伤的重物坠落模型。方法与步骤 创伤性脑损伤后,从第1天至第28天,动物分别接受单独的强力霉素(50和100毫克/千克;口服)、生育酚(5和10毫克/千克;口服)以及强力霉素与生育酚联合用药(50和10毫克/千克;口服)治疗。从第1天至第28天,每周进行行为参数检测。在第29天,处死动物,取纹状体和皮质进行匀浆,以评估生化指标(脂质过氧化、亚硝酸盐和谷胱甘肽)、神经炎症指标(白细胞介素-6、白细胞介素-1β和肿瘤坏死因子-α)以及神经递质(多巴胺、去甲肾上腺素、5-羟色胺、γ-氨基丁酸和谷氨酸)。主要结果 创伤性脑损伤的诱导显著降低了运动活性、识别记忆,增加了神经炎症标志物,并使神经递质水平失衡。单独及联合使用强力霉素和生育酚治疗显著减轻了运动活性,改善了记忆识别,减轻了神经炎症,维持了氧化平衡,并恢复了神经递质水平。结论 强力霉素和生育酚的神经保护作用可能归因于其抗炎和自由基清除机制。缩写词 TBI:创伤性脑损伤;Doxy:强力霉素;Toco:生育酚;LPO:脂质过氧化;MDA:丙二醛;TNF-α:肿瘤坏死因子-α;IL-1β:白细胞介素-1β;GSH:谷胱甘肽;GABA:γ-氨基丁酸

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