Dietary choline supplementation improves behavioral, histological, and neurochemical outcomes in a rat model of traumatic brain injury

Dietary choline supplementation improves behavioral, histological, and neurochemical outcomes in a rat model of traumatic brain injury
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DOI:
10.1089/neu.2008.0516
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发表时间:
2008-08-01
影响因子:
4.2
通讯作者:
Pauly, James R.
Pauly, James R.
中科院分区:
医学2区
文献类型:
--
作者:
Guseva, Maria V.;Hopkins, Deann M.;Pauly, James R.

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迫切需要安全有效地减轻创伤性脑损伤(TBI)后神经功能缺损程度的新药理学方法。可以长期使用的非侵入性方法可能特别有用。我们实验室以前的研究假设,TBI诱导的海马和皮质α 7神经元烟碱胆碱能受体(nAChR)表达的减少可能有助于脑损伤后的认知障碍。本研究的目的是确定是否低效力,但选择性α 7 nAChR激动剂胆碱可能是一个有用的治疗TBI大鼠模型的神经功能的改善结果。雄性Sprague-Dawley大鼠在实验性脑损伤(1.5 mm皮质挫伤)前2周和整个恢复期暴露于对照或补充胆碱的饮食。在Morris水迷宫测试中,饮食胆碱补充导致空间记忆的适度改善。此外,胆碱治疗导致显着的皮质组织保留,减少脑炎症,并正常化一些TBI诱导的nAChR表达的缺陷。这项研究的结果表明,α 7 nAChR激动剂可能是有用的药物,以促进脑损伤后的恢复。
Novel pharmacological approaches that safely and effectively lessen the degree of neurological impairment following traumatic brain injury (TBI) are sorely needed. Non-invasive approaches that could be used over an extended periods of time might be particularly useful. Previous studies from our lab have hypothesized that TBI-induced decreases in hippocampal and cortical alpha 7 neuronal nicotinic cholinergic receptor (nAChR) expression might contribute to cognitive impairment that follows brain injury. The purpose of this study was to determine whether the low-potency, but selective alpha 7 nAChR agonist choline might be a useful treatment for improvement of neurological outcome in a rat model of TBI. Male Sprague-Dawley rats were exposed to control or choline-supplemented diets for 2 weeks prior to experimental brain injury (1.5-mm cortical contusion injury) and throughout the recovery phase. Dietary choline supplementation resulted in a modest degree of improvement in spatial memory as assessed in the Morris water maze test. In addition, choline treatment resulted in significant cortical tissue sparing, reduced brain inflammation, and normalized some TBI-induced deficits in nAChR expression. The results of this study suggest that alpha 7 nAChR agonists may be useful drugs to enhance recovery following brain injury.