Journal of Stroke & Cerebrovascular Diseases ( IF 2.5 ) Pub Date : 2021-09-20 , DOI: 10.1016/j.jstrokecerebrovasdis.2021.106105 Ulkan Kilic 1 , Birsen Elibol 2 , Merve Beker 3 , Burcugul Altug-Tasa 4 , Ahmet Burak Caglayan 5 , Mustafa Caglar Beker 5 , Bayram Yilmaz 6 , Ertugrul Kilic 5
Objectives
Post-ischemic inflammation leads to apoptosis as an indirect cause of functional disabilities after the stroke. Melatonin may be a good candidate for the stroke recovery because of its anti-inflammatory effects. Therefore, we investigated the effect of melatonin on inflammation in the functional recovery of brain by evaluating ipsilesional and contralesional alterations.
Materials and Methods
Melatonin (4 mg/kg/day) was intraperitoneally administered into the mice from the 3rd to the 55th day of the post-ischemia after 30 min of middle cerebral artery occlusion.
Results
Melatonin produced a functional recovery by reducing the emigration of the circulatory leukocytes and the local microglial activation within the ischemic brain. Overall, the expression of the inflammation-related genes reduced upon melatonin treatment in the ischemic hemisphere. On the other hand, the expression level of the inflammatory cytokine genes raised in the contralateral hemisphere at the 55th day of the post-ischemia. Furthermore, melatonin triggers an increase in the iNOS expression and a decrease in the nNOS expression in the ipsilateral hemisphere at the earlier times in the post-ischemic recovery. At the 55th day of the post-ischemic recovery, melatonin administration enhanced the eNOS and nNOS protein expressions.
Conclusions
The present molecular, biological, and histological data have revealed broad anti-inflammatory effects of melatonin in both hemispheres with distinct temporal and spatial patterns at different phases of post-stroke recovery. These outcomes also established that melatonin act recruitment of contralesional rather than of ipsilesional.
中文翻译:
炎症细胞因子正在发挥作用:由于延迟使用褪黑激素,脑缺血后的脑可塑性和恢复
目标
缺血后炎症导致细胞凋亡作为中风后功能障碍的间接原因。褪黑激素可能是中风恢复的良好候选者,因为它具有抗炎作用。因此,我们通过评估同侧和对侧变化来研究褪黑激素对大脑功能恢复中炎症的影响。
材料和方法
大脑中动脉闭塞30分钟后,从缺血后第3天到第55天给小鼠腹腔注射褪黑激素(4mg/kg/天) 。
结果
褪黑激素通过减少循环白细胞的迁移和缺血性脑内的局部小胶质细胞活化来产生功能恢复。总体而言,缺血半球褪黑激素治疗后炎症相关基因的表达降低。另一方面,缺血后第55天,对侧半球炎性细胞因子基因的表达水平升高。此外,褪黑激素会在缺血后恢复的早期触发同侧半球中 iNOS 表达的增加和 nNOS 表达的减少。在缺血后恢复的第 55 天,褪黑激素给药增强了 eNOS 和 nNOS 蛋白的表达。
结论
目前的分子、生物学和组织学数据揭示了褪黑激素在两个半球的广泛抗炎作用,在中风后恢复的不同阶段具有不同的时间和空间模式。这些结果还证实,褪黑激素作用于对侧而不是同侧的募集。