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首页> 外文期刊>Journal of neuroinflammation >Tumor necrosis factor alpha antagonism improves neurological recovery in murine intracerebral hemorrhage
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Tumor necrosis factor alpha antagonism improves neurological recovery in murine intracerebral hemorrhage

机译：肿瘤坏死因子α拮抗作用可改善鼠脑出血的神经恢复

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Background Intracerebral hemorrhage (ICH) is a devastating stroke subtype characterized by a prominent neuroinflammatory response. Antagonism of pro-inflammatory cytokines by specific antibodies represents a compelling therapeutic strategy to improve neurological outcome in patients after ICH. To test this hypothesis, the tumor necrosis factor alpha (TNF-α) antibody CNTO5048 was administered to mice after ICH induction, and histological and functional endpoints were assessed. Methods Using 10 to 12-week-old C57BL/6J male mice, ICH was induced by collagenase injection into the left basal ganglia. Brain TNF-α concentration, microglia activation/macrophage recruitment, hematoma volume, cerebral edema, and rotorod latency were assessed in mice treated with the TNF-α antibody, CNTO5048, or vehicle. Results After ICH induction, mice treated with CNTO5048 demonstrated reduction in microglial activation/macrophage recruitment compared to vehicle-treated animals, as assessed by unbiased stereology (P = 0.049). This reduction in F4/80-positive cells was associated with a reduction in cleaved caspase-3 (P = 0.046) and cerebral edema (P = 0.026) despite similar hematoma volumes, when compared to mice treated with vehicle control. Treatment with CNTO5048 after ICH induction was associated with a reduction in functional deficit when compared to mice treated with vehicle control, as assessed by rotorod latencies (P = 0.024). Conclusions Post-injury treatment with the TNF-α antibody CNTO5048 results in less neuroinflammation and improved functional outcomes in a murine model of ICH.
机译：背景脑出血（ICH）是一种毁灭性的中风亚型，特征在于突出的神经炎症反应。特异性抗体与促炎细胞因子的拮抗作用代表了一种令人信服的治疗策略，可改善ICH后患者的神经功能。为了检验该假设，在ICH诱导后向小鼠施用肿瘤坏死因子α（TNF-α）抗体CNTO5048，并评估了组织学和功能终点。方法用10至12周龄的C57BL / 6J雄性小鼠，通过胶原酶注射入左基底神经节诱导ICH。在用TNF-α抗体，CNTO5048或溶媒治疗的小鼠中评估了脑TNF-α浓度，小胶质细胞活化/巨噬细胞募集，血肿量，脑水肿和旋翼潜伏期。结果在ICH诱导后，用CNTO5048处理的小鼠与通过媒介物处理的动物相比，显示了小胶质细胞激活/巨噬细胞募集的减少，这是通过无偏立体学评估的（P = 0.049）。与使用媒介物对照治疗的小鼠相比，尽管血肿体积相似，但F4 / 80阳性细胞的这种减少与裂解的caspase-3（P = 0.046）和脑水肿（P = 0.026）的减少有关。与用媒介物对照治疗的小鼠相比，用ICH诱导后用CNTO5048进行的治疗与功能障碍的减少有关，如通过旋翼飞机潜伏期评估的那样（P = 0.024）。结论TNF-α抗体CNTO5048损伤后治疗在ICH鼠模型中可减少神经炎症并改善功能结局。

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