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局部脑内注射脂肪乳剂对大鼠兴奋毒性损伤的神经保护作用。

Neuroprotection from Excitotoxic Injury by Local Administration of Lipid Emulsion into the Brain of Rats.

机构信息

Department of Physiology, Yonsei University College of Medicine, Seoul 03722, Korea.

Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.

出版信息

Int J Mol Sci. 2020 Apr 14;21(8):2706. doi: 10.3390/ijms21082706.

DOI:10.3390/ijms21082706
PMID:32295117
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7215821/
Abstract

Lipid emulsion was recently shown to attenuate cell death caused by excitotoxic conditions in the heart. There are key similarities between neurons and cardiomyocytes, such as excitability and conductibility, which yield vulnerability to excitotoxic conditions. However, systematic investigations on the protective effects of lipid emulsion in the central nervous system are still lacking. This study aimed to determine the neuroprotective effects of lipid emulsion in an in vivo rat model of kainic acid-induced excitotoxicity through intrahippocampal microinjections. Kainic acid and/or lipid emulsion-injected rats were subjected to the passive avoidance test and elevated plus maze for behavioral assessment. Rats were sacrificed at 24 h and 72 h after kainic acid injections for molecular study, including immunoblotting and qPCR. Brains were also cryosectioned for morphological analysis through cresyl violet staining and Fluorojade-C staining. Anxiety and memory functions were significantly preserved in 1% lipid emulsion-treated rats. Lipid emulsion was dose-dependent on the protein expression of β-catenin and the phosphorylation of GSK3-β and Akt. Wnt1 mRNA expression was elevated in lipid emulsion-treated rats compared to the vehicle. Neurodegeneration was significantly reduced mainly in the CA1 region with increased cell survival. Our results suggest that lipid emulsion has neuroprotective effects against excitotoxic conditions in the brain and may provide new insight into its potential therapeutic utility.

摘要

脂质乳剂最近被证明可以减轻心脏兴奋毒性条件下的细胞死亡。神经元和心肌细胞之间存在关键的相似性，如兴奋性和传导性，这使得它们容易受到兴奋毒性条件的影响。然而，脂质乳剂在中枢神经系统中的保护作用的系统研究仍然缺乏。本研究旨在通过海马内微量注射，在体内大鼠海人酸诱导兴奋毒性模型中确定脂质乳剂的神经保护作用。海人酸和/或脂质乳剂注射大鼠接受被动回避测试和高架十字迷宫进行行为评估。在海人酸注射后 24 小时和 72 小时处死大鼠，进行分子研究，包括免疫印迹和 qPCR。通过 Cresyl Violet 染色和 Fluorojade-C 染色对大脑进行冷冻切片进行形态分析。1%脂质乳剂处理的大鼠焦虑和记忆功能明显得到保留。脂质乳剂对 β-catenin 蛋白表达和 GSK3-β 和 Akt 的磷酸化呈剂量依赖性。与载体相比，脂质乳剂处理的大鼠 Wnt1 mRNA 表达升高。神经退行性变主要在 CA1 区减少，细胞存活率增加。我们的结果表明，脂质乳剂对大脑兴奋毒性条件具有神经保护作用，并可能为其潜在的治疗用途提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/98276fc7d106/ijms-21-02706-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/348ac433793d/ijms-21-02706-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/21ab593e4785/ijms-21-02706-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/ad0554b84460/ijms-21-02706-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/98276fc7d106/ijms-21-02706-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/348ac433793d/ijms-21-02706-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/493681bd93e5/ijms-21-02706-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/94251352464e/ijms-21-02706-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/05a0af645e1d/ijms-21-02706-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/21ab593e4785/ijms-21-02706-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/ad0554b84460/ijms-21-02706-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9432/7215821/98276fc7d106/ijms-21-02706-g007.jpg

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