Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Brain Res Bull. 2018 Oct;143:217-224. doi: 10.1016/j.brainresbull.2018.09.011. Epub 2018 Sep 19.
Spinal cord injury (SCI) is a debilitating condition in which inflammatory responses in the secondary phase of injury leads to long lasting sensory-motor dysfunction. The medicinal therapy of SCI complications is still a clinical challenge. Understanding the molecular pathways underlying the progress of damage will help to find new therapeutic candidates. Astaxanthin (AST) is a ketocarotenoid which has shown anti-inflammatory effects in models of traumatic brain injury. In the present study, we examined its potential in the elimination of SCI damage through glutamatergic-phospo p38 mitogen-activated protein kinase (p-p38MAPK) signaling pathway. Inflammatory response, histopathological changes and sensory-motor function were also investigated in a severe compression model of SCI in male rats. The results of acetone drop and inclined plane tests indicated the promising role of AST in improving sensory and motor function of SCI rats. AST decreased the expression of n-methyl-d-aspartate receptor subunit 2B (NR2B) and p-p38MAPK as inflammatory signaling mediators as well as tumor necrosis factor-α (TNF-α) as an inflammatory cytokine, following compression SCI. The histopathological study culminated in preserved white mater and motor neurons beyond the injury level in rostral and caudal parts. The results show the potential of AST to inhibit glutamate-initiated signaling pathway and inflammatory reactions in the secondary phase of SCI, and suggest it as a promising candidate to enhance functional recovery after SCI.
脊髓损伤(SCI)是一种使人衰弱的疾病,其中损伤的继发阶段的炎症反应会导致长期的感觉运动功能障碍。SCI 并发症的药物治疗仍然是一个临床挑战。了解损伤进展的分子途径将有助于找到新的治疗候选物。虾青素(AST)是一种酮类胡萝卜素,在创伤性脑损伤模型中显示出抗炎作用。在本研究中,我们通过谷氨酰胺磷酸 p38 丝裂原激活蛋白激酶(p-p38MAPK)信号通路研究了其在消除 SCI 损伤中的潜力。还在雄性大鼠的严重压迫性 SCI 模型中研究了炎症反应、组织病理学变化和感觉运动功能。丙酮滴和斜面试验的结果表明,AST 有望改善 SCI 大鼠的感觉和运动功能。AST 降低了 N-甲基-D-天冬氨酸受体亚单位 2B(NR2B)和 p-p38MAPK 的表达,作为炎症信号介质,以及肿瘤坏死因子-α(TNF-α)作为炎症细胞因子,继压缩性 SCI 之后。组织病理学研究的结果表明,在损伤水平的头侧和尾侧部分,白质和运动神经元得到了保存。结果表明,AST 具有抑制谷氨酸引发的信号通路和 SCI 继发阶段炎症反应的潜力,并表明它是增强 SCI 后功能恢复的有希望的候选物。