Cordycepin confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury

• DOI: 10.1186/s12974-021-02188-x
• Publication Date: 2021-06-15T13:03:59Z
• Authors: Pengju Wei; Ke Wang; Chen Luo; Yichen Huang; Dilidaer Misilimu; Huimei Wen; Peng Jin; Chuhua Li; Ye Gong; Yanqin Gao
• Keywords: Cordycepin; Infiltration (HVAC)

The secondary injury caused by traumatic brain (TBI), especially white matter (WMI), is highly sensitive to neuroinflammation, which further leads unfavored long-term outcomes. Although the cross-talk between three active events, immune cell infiltration, BBB breakdown, and proinflammatory microglial/macrophage polarization, plays a role in vicious cycle, its mechanisms are not fully understood. It has been reported that cordycepin, an extract from Cordyceps militaris, can inhibit TBI-induced neuroinflammation although effects of cordycepin remain unknown. Here, we report our investigation cordycepin's neuroprotective function underlying immunological mechanism.TBI mice model was established with controlled cortical impact (CCI) method. Cordycepin intraperitoneally administered twice daily for week. Neurological outcomes were assessed behavioral tests, including grid walking test, cylinder wire hang rotarod test. Immunofluorescence staining, transmission electron microscopy, electrophysiology recording employed assess histological functional lesions. Quantitative-PCR flow cytometry used detect neuroinflammation. tracers Sulfo-NHS-biotin Evans blue blood-brain barrier (BBB) leakage. Western blot gelatin zymography analyze protein activity or expression. Neutrophil depletion vivo performed via using Ly6G antibody intraperitoneal injection.Cordycepin administration ameliorated neurological deficits reduced neuronal tissue loss TBI mice. Meanwhile, integrity also preserved, revealed multiple dimensions, such as morphology, histology, ultrastructure, electrical conductivity. inhibited microglia/macrophage pro-inflammatory polarization promoted anti-inflammatory after TBI. breach attenuated at 3 days suppressed activities MMP-2 MMP-9 neutrophil infiltration Moreover, provided cordycepin-like effect, united did show benefit superposition.The suppressing TBI, thereby preserving changing polarization. These findings provide significant clinical potentials improve quality life patients.