Anti-inflammatory and anti-apoptotic activity of synaptamide improves the morphological state of neurons in traumatic brain injury

IF 4.6 2区 医学 Q1 NEUROSCIENCES
Igor Manzhulo, Anna Tyrtyshnaia, Anastasia Egoraeva, Darya Ivashkevich, Alexander Girich, Olga Manzhulo
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Abstract

Traumatic brain injuries (TBI) of varying severity are becoming more frequent all over the world. The process of neuroinflammation, in which macrophages and microglia are key players, underlies all types of brain damage. The present study focuses on evaluating the therapeutic potential of N-docosahexaenoylethanolamine (DHEA, synaptamide), which is an endogenous metabolite of docosahexaenoic acid in traumatic brain injury. Previously, several in vitro and in vivo models have shown significant anti-neuroinflammatory and synaptogenic activity of synaptamide. The results of the present study show that synaptamide by subcutaneous administration (10 mg/kg/day, 7 days) exerts anti-inflammatory and anti-apoptotic effects in the thalamus and cerebral cortex of experimental animals (male C57BL/6 mice). Were analyzed the dynamics of changes in the activity of Iba-1- and CD68-positive microglia/macrophages, the level of production of pro-inflammatory cytokines (IL1β, IL6, TNFα) and pro-apoptotic proteins (Bad, Bax), the expression of pro- and anti-inflammatory markers (CD68, CD206, arg-1). ATF3 transcription factor distribution and neuronal state in the thalamus and cerebral cortex of animals with craniotomy, traumatic brain injury, and therapy are quantitatively assessed. The obtained data showed that synaptamide: (1) has no effect on the total pool of microglia/macrophages; (2) inhibits the activity of pro-inflammatory microglia/macrophages and cytokines they produce; (3) increases the expression of CD206 but not arg-1; (4) has anti-apoptotic effect and (5) improves the morphological state of neurons. The results obtained confirm the high therapeutic potential of synaptamide in the therapy of traumatic brain injury.

突触酰胺的抗炎和抗凋亡活性可改善脑外伤神经元的形态状态。
世界各地不同程度的创伤性脑损伤(TBI)越来越频繁。神经炎症过程是所有类型脑损伤的基础,而巨噬细胞和小胶质细胞是其中的关键角色。本研究的重点是评估 N-二十二碳六烯醇胺(DHEA,突触酰胺)的治疗潜力,它是二十二碳六烯酸在创伤性脑损伤中的内源性代谢产物。此前,一些体外和体内模型显示,突触酰胺具有显著的抗神经炎症和突触生成活性。本研究结果表明,皮下注射突触酰胺(10 毫克/千克/天,7 天)对实验动物(雄性 C57BL/6 小鼠)的丘脑和大脑皮层具有抗炎和抗凋亡作用。分析了 Iba-1 和 CD68 阳性小胶质细胞/巨噬细胞活性的动态变化、促炎细胞因子(IL1β、IL6、TNFα)和促凋亡蛋白(Bad、Bax)的产生水平、促炎和抗炎标记物(CD68、CD206、arg-1)的表达。定量评估了开颅手术、脑外伤和治疗动物丘脑和大脑皮层中 ATF3 转录因子的分布和神经元状态。所得数据显示,突触酰胺:(1)对小胶质细胞/巨噬细胞的总量没有影响;(2)抑制促炎性小胶质细胞/巨噬细胞的活性及其产生的细胞因子;(3)增加 CD206 的表达,但不增加 arg-1;(4)具有抗凋亡作用;(5)改善神经元的形态状态。这些结果证实了突触酰胺在治疗脑外伤方面的巨大潜力。
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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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