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首页> 外文期刊>Journal of neuroinflammation >Treatment with an anti-CD11d integrin antibody reduces neuroinflammation and improves outcome in a rat model of repeated concussion
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Treatment with an anti-CD11d integrin antibody reduces neuroinflammation and improves outcome in a rat model of repeated concussion

机译：在反复发作的大鼠模型中，用抗CD11d整合素抗体治疗可减少神经炎症并改善预后

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Background Concussions account for the majority of traumatic brain injuries (TBI) and can result in cumulative damage, neurodegeneration, and chronic neurological abnormalities. The underlying mechanisms of these detrimental effects remain poorly understood and there are presently no specific treatments for concussions. Neuroinflammation is a major contributor to secondary damage following more severe TBI, and recent findings from our laboratory suggest it may be involved in the cumulative properties of repeated concussion. We previously found that an anti-CD11d monoclonal antibody that blocks the CD11d/CD18 integrin and adhesion molecule interaction following severe experimental TBI reduces neuroinflammation, oxidative activity, and tissue damage, and improves functional recovery. As similar processes may be involved in repeated concussion, here we studied the effects of the anti-CD11d treatment in a rat model of repeated concussion. Methods Rats were treated 2 h and 24 h after each of three repeated mild lateral fluid percussion injuries with either the CD11d antibody or an isotype-matched control antibody, 1B7. Injuries were separated by a five-day inter-injury interval. After the final treatment and either an acute (24 to 72 h post-injury) or chronic (8 weeks post-injury) recovery period had elapsed, behavioral and pathological outcomes were examined. Results The anti-CD11d treatment reduced neutrophil and macrophage levels in the injured brain with concomitant reductions in lipid peroxidation, astrocyte activation, amyloid precursor protein accumulation, and neuronal loss. The anti-CD11d treatment also improved outcome on tasks of cognition, sensorimotor ability, and anxiety. Conclusions These findings demonstrate that reducing inflammation after repeated mild brain injury in rats leads to improved behavioral outcomes and that the anti-CD11d treatment may be a viable therapy to improve post-concussion outcomes.
机译：背景脑震荡是脑外伤（TBI）的主要来源，可导致累积性损伤，神经变性和慢性神经系统异常。这些有害作用的潜在机制仍知之甚少，目前尚无针对脑震荡的具体治疗方法。神经炎症是导致更严重的TBI后继发性损伤的主要因素，我们实验室的最新发现表明，它可能与反复脑震荡的累积特性有关。我们先前发现，在严重的实验性TBI后，阻断CD11d / CD18整合素和粘附分子相互作用的抗CD11d单克隆抗体可减少神经炎症，氧化活性和组织损伤，并改善功能恢复。由于重复性脑震荡可能涉及相似的过程，因此我们在反复性脑震荡的大鼠模型中研究了抗CD11d治疗的作用。方法用CD11d抗体或同种型匹配的对照抗体1B7对3次反复的轻度侧向液体敲击损伤中的每只分别在2h和24h进行治疗。受伤间隔为五天。在最终治疗后，无论是急性的（受伤后24至72小时）还是慢性的（受伤后8周）恢复期都过去了，检查了行为和病理结果。结果抗CD11d治疗可减少受伤脑中的中性粒细胞和巨噬细胞水平，并同时减少脂质过氧化，星形胶质细胞活化，淀粉样蛋白前体蛋白积累和神经元丢失。抗CD11d治疗还改善了认知，感觉运动能力和焦虑任务的结局。结论这些发现表明，减轻大鼠反复轻度脑损伤后的炎症可改善行为预后，抗CD11d治疗可能是改善脑震荡后预后的可行疗法。

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