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Neonatal microglia and proteinase inhibitors-treated adult microglia improve traumatic brain injury in rats by resolving the neuroinflammation
Bioengineering & Translational Medicine ( IF 7.4 ) Pub Date : 2021-08-21 , DOI: 10.1002/btm2.10249
Ping Zheng 1 , Qingke Bai 2 , Jiugeng Feng 3 , Bing Zhao 4 , Jian Duan 3 , Lin Zhao 5 , Ning Liu 5 , Dabin Ren 4 , Shufeng Zou 3 , Wei Chen 1, 3, 4
Affiliation  

Microglia participate in the regulation of neuroinflammation caused by traumatic brain injury (TBI). This research aimed to explore the repair effects of intracranial injection of neonatal microglia or protease-treated adult microglia on TBI in rat model. Lateral fluid percussion injury was used to establish rat brain injury model. E64 and serpinA3N were employed for the treatment of adult microglia. Cleaved caspase-3 level was analyzed through immunoblotting assay. Enzyme-linked immunosorbent assay was employed to analyze cytokine and chemokine levels. Astrocytosis and microgliosis were shown by immunofluorescence. The cognitive function of rats was analyzed by water maze. The injection of neonatal microglia inhibited cell apoptosis, reduced astrocytosis and microgliosis, decreased the level of chemokines and cytokines in cortex and ipsilateral hippocampus, and improved cognitive function of TBI rat model. The transplantation of peptidase inhibitors-treated adult microglia also inhibited cell apoptosis, reduced astrocytosis and microgliosis, and improved cognitive function of rats with TBI. The transplantation of either neonatal microglia or peptidase inhibitors-treated adult microglia significantly inhibited the pathogenesis of TBI in rat model, while untreated adult microglia showed no significant effect.

中文翻译:

新生儿小胶质细胞和蛋白酶抑制剂治疗的成年小胶质细胞通过解决神经炎症改善大鼠创伤性脑损伤

小胶质细胞参与调节由创伤性脑损伤 (TBI) 引起的神经炎症。本研究旨在探讨颅内注射新生小胶质细胞或经蛋白酶处理的成人小胶质细胞对大鼠TBI的修复作用。采用侧液冲击损伤法建立大鼠脑损伤模型。E64 和 serpinA3N 用于治疗成人小胶质细胞。通过免疫印迹测定分析切割的 caspase-3 水平。酶联免疫吸附试验用于分析细胞因子和趋化因子水平。免疫荧光显示星形细胞增多症和小胶质细胞增多症。通过水迷宫分析大鼠的认知功能。新生儿小胶质细胞的注射抑制细胞凋亡,减少星形胶质细胞增生和小胶质细胞增生,降低皮质和同侧海马趋化因子和细胞因子的水平,改善TBI大鼠模型的认知功能。肽酶抑制剂治疗的成年小胶质细胞的移植也抑制了细胞凋亡,减少了星形细胞增多症和小胶质细胞增生,并改善了 TBI 大鼠的认知功能。新生小胶质细胞移植或肽酶抑制剂治疗的成年小胶质细胞显着抑制大鼠模型中TBI的发病机制,而未经治疗的成年小胶质细胞没有显着影响。
更新日期:2021-08-21
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