Cordycepin confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury.
Cordycepin confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury.
复制标题
虫草素通过抑制创伤性脑损伤后的中性粒细胞浸润和神经炎症来提供长期的神经保护
DOI：
10.1186/s12974-021-02188-x
复制
发表时间：
2021-06-15
影响因子：
9.3
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Wei P;Wang K;Luo C;Huang Y;Misilimu D;Wen H;Jin P;Li C;Gong Y;Gao Y
背景脑外伤（traumatic brain injury，TBI）后继发性损伤，尤其是白色物质损伤（white matter injury，TBI），对神经炎症反应高度敏感，导致远期预后不良。虽然三个活跃事件之间的相互作用，免疫细胞浸润，血脑屏障破坏，和促炎性小胶质细胞/巨噬细胞极化，在恶性循环中发挥作用，其机制尚未完全理解。蛹虫草素（Cordycepin militaris）的提取物具有抑制TBI诱导的神经炎症的作用，但其长期作用尚不清楚。在这里，我们报告了我们对虫草素长期神经保护功能及其潜在免疫机制的研究。方法采用控制皮质撞击（CCI）方法建立TBI小鼠模型。虫草素腹腔注射，每天两次，持续一周。通过行为测试评估神经功能结局，包括网格行走试验、圆柱试验、钢丝悬挂试验和旋转棒试验。采用免疫荧光染色、透射电子显微镜和电生理记录来评估组织学和功能性病变。定量PCR和流式细胞术检测神经炎症。用Sulfo-NHS-biotin和Evans blue示踪剂检测血脑屏障（BBB）渗漏。蛋白质印迹和明胶酶谱分析蛋白质活性或表达。通过使用Ly 6 G抗体腹膜内injection.ResultsCordycepin给药改善了长期的神经功能缺损，减少了TBI小鼠的神经组织损失。同时，白色物质的长期完整性也得到了保存，这在形态学、组织学、超微结构和电导率等多个维度上得到了揭示。虫草素给药抑制小胶质细胞/巨噬细胞促炎极化，并促进TBI后的抗炎极化。在TBI后3天给予虫草素可减弱BBB破坏。虫草素可抑制创伤后3d MMP-2、MMP-9活性及中性粒细胞浸润。此外，中性粒细胞耗竭提供了虫草素样的效果，虫草素管理与中性粒细胞耗竭联合并没有显示出叠加的好处。ConclusionsThe long-term neuroprotective function of cordycepin via suppressing neutrophil infiltration after TBI，从而保持血脑屏障的完整性和改变小胶质细胞/巨噬细胞极化。这些发现为改善TBI患者的生活质量提供了重要的临床潜力。
BackgroundThe secondary injury caused by traumatic brain injury (TBI), especially white matter injury (WMI), is highly sensitive to neuroinflammation, which further leads to unfavored long-term outcomes. Although the cross-talk between the three active events, immune cell infiltration, BBB breakdown, and proinflammatory microglial/macrophage polarization, plays a role in the vicious cycle, its mechanisms are not fully understood. It has been reported that cordycepin, an extract fromCordyceps militaris, can inhibit TBI-induced neuroinflammation although the long-term effects of cordycepin remain unknown. Here, we report our investigation of cordycepin’s long-term neuroprotective function and its underlying immunological mechanism.MethodsTBI mice model was established with a controlled cortical impact (CCI) method. Cordycepin was intraperitoneally administered twice daily for a week. Neurological outcomes were assessed by behavioral tests, including grid walking test, cylinder test, wire hang test, and rotarod test. Immunofluorescence staining, transmission electron microscopy, and electrophysiology recording were employed to assess histological and functional lesions. Quantitative-PCR and flow cytometry were used to detect neuroinflammation. The tracers of Sulfo-NHS-biotin and Evans blue were assessed for the blood-brain barrier (BBB) leakage. Western blot and gelatin zymography were used to analyze protein activity or expression. Neutrophil depletion in vivo was performed via using Ly6G antibody intraperitoneal injection.ResultsCordycepin administration ameliorated long-term neurological deficits and reduced neuronal tissue loss in TBI mice. Meanwhile, the long-term integrity of white matter was also preserved, which was revealed in multiple dimensions, such as morphology, histology, ultrastructure, and electrical conductivity. Cordycepin administration inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization after TBI. BBB breach was attenuated by cordycepin administration at 3 days after TBI. Cordycepin suppressed the activities of MMP-2 and MMP-9 and the neutrophil infiltration at 3 days after TBI. Moreover, neutrophil depletion provided a cordycepin-like effect, and cordycepin administration united with neutrophil depletion did not show a benefit of superposition.ConclusionsThe long-term neuroprotective function of cordycepin via suppressing neutrophil infiltration after TBI, thereby preserving BBB integrity and changing microglia/macrophage polarization. These findings provide significant clinical potentials to improve the quality of life for TBI patients.
登录
查看更多内容
丙酮酸乙酯可改善大鼠脑外伤后的白质重塑。
影响因子：
5.5
作者：
Mao L;Sun L;Sun J;Sun B;Gao Y;Shi H
通讯作者：
Shi H
趋化因子样因子 1（一种新型 C-C 趋化因子）的中和作用可通过 MAPK 途径抑制中性粒细胞浸润，从而预防局灶性脑缺血
影响因子：
9.3
作者：
Kong LL;Wang ZY;Han N;Zhuang XM;Wang ZZ;Li H;Chen NH
通讯作者：
Chen NH
影响因子：
15.9
作者：
Dorhoi, Anca;Iannaccone, Marco;Kaufmann, Stefan H. E.
通讯作者：
Kaufmann, Stefan H. E.
影响因子：
6.3
作者：
Edwards, Danielle N.;Salmeron, Kathleen;Bix, Gregory J.
通讯作者：
Bix, Gregory J.
影响因子：
--
作者：
Goldim, Mariana Pereira de Souza;Della Giustina, Amanda;Petronilho, Fabricia
通讯作者：
Petronilho, Fabricia