Ethyl pyruvate improves white matter remodeling in rats after traumatic brain injury.
Ethyl pyruvate improves white matter remodeling in rats after traumatic brain injury.
复制标题
丙酮酸乙酯可改善大鼠脑外伤后的白质重塑。
DOI：
10.1111/cns.13534
复制
发表时间：
2021-01
影响因子：
5.5
通讯作者：
Shi H
中科院分区：
文献类型：
--
作者：
Mao L;Sun L;Sun J;Sun B;Gao Y;Shi H
重度创伤性脑损伤（TBI）导致与白色损伤（白质损伤）相关的长期神经功能缺损。丙酮酸乙酯（EP）是内源性能量底物丙酮酸的一种简单衍生物，具有神经保护作用，但其在恢复中的作用尚未被探索。本研究使用行为测试和白色组织学分析检查了EP治疗对TBI后大鼠的影响，直至损伤后28天。麻醉的成年大鼠通过控制皮质撞击进行TBI。术后15 min及12、24、36、48、60 h分别腹腔注射EP或Ringers液（RS）。感觉运动缺陷进行了评估，直到第21天TBI后，由四个独立的测试。免疫荧光和透射电子显微镜（TEM）进行评估白色物质损伤。通过免疫组织化学或真实的时间PCR检查TBI后14天的小胶质细胞活化和相关炎症分子。在这里，我们证明，EP改善感觉运动功能TBI后，以及改善白色物质的结果TBI后28天，如减少髓鞘丢失所示。此外，在TBI恢复的急性期给予EP将小胶质细胞极化向抗炎M2表型转移，调节炎症相关因子的释放。EP治疗可以通过调节小胶质细胞向M2的极化来保护TBI诱导的脑缺血。
Severe traumatic brain injury (TBI) results in long‐term neurological deficits associated with white matter injury (WMI). Ethyl pyruvate (EP) is a simple derivative of the endogenous energy substrate pyruvate with neuroprotective properties, but its role in recovery from WMI has not been explored. This study examines the effect of EP treatment on rats following TBI using behavioral tests and white matter histological analysis up to 28 days post‐injury. Anaesthetised adult rats were subjected to TBI by controlled cortical impact. After surgery, EP or Ringers solution (RS) was administrated intraperitoneally at 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Sensorimotor deficits were evaluated up to day 21 after TBI by four independent tests. Immunofluorescence and transmission electron microscopy (TEM) were performed to assess white matter injury. Microglia activation and related inflammatory molecules were examined up to day 14 after TBI by immunohistochemistry or real‐time PCR. Here, we demonstrate that EP improves sensorimotor function following TBI as well as improves white matter outcomes up to 28 d after TBI, as shown by reduced myelin loss. Furthermore, EP administration during the acute phase of TBI recovery shifted microglia polarization toward the anti‐inflammatoryM2 phenotype, modulating the release of inflammatory‐related factors. EP treatment may protect TBI‐induced WMI via modulating microglia polarization toward M2.
登录
查看更多内容
丙酮酸乙酯可防止血脑屏障损伤并改善创伤性脑损伤大鼠模型的长期神经学结果。
影响因子：
5.5
作者：
Shi H;Wang HL;Pu HJ;Shi YJ;Zhang J;Zhang WT;Wang GH;Hu XM;Leak RK;Chen J;Gao YQ
通讯作者：
Gao YQ
褪黑激素通过 STAT3 通路调节小胶质细胞/巨噬细胞极化至抗炎表型，从而预防缺血性中风
影响因子：
5.5
作者：
Liu, Zong-Jian;Ran, Yuan-Yuan;Xi, Jia-Ning
通讯作者：
Xi, Jia-Ning
影响因子：
14.5
作者：
Jolly, Amy E.;Scott, Gregory T.;Hampshire, Adam H.
通讯作者：
Hampshire, Adam H.
影响因子：
3.4
作者：
Moreira da Silva, Nadia;Cowie, Christopher J. A.;Taylor, Peter Neal
通讯作者：
Taylor, Peter Neal
影响因子：
5.5
作者：
Mouihate, Abdeslam;Kalakh, Samah
通讯作者：
Kalakh, Samah