PDF(Pubmed)
Abstract：
Epidural and subdural hematomas are commonly associated with traumatic brain injury. While surgical removal is the primary intervention for these hematomas, it is also critical to prevent and reduce complications such as post-traumatic epilepsy, which may result from inflammatory responses in the injured brain areas. In the present study, we observed that high mobility group box-1 (HMGB1) decreased in the injured brain area beneath the epidural hematoma (EDH) in rats, concurrent with elevated plasma levels of HMGB1. Anti-HMGB1 monoclonal antibody therapy strongly inhibited both HMGB1 release and the subsequent increase in plasma levels. Moreover, this treatment suppressed the up-regulation of inflammatory cytokines and related molecules such as interleukin-1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in the injured areas. Our in vitro experiments using SH-SY5Y demonstrated that hematoma components-thrombin, heme, and ferrous ion- prompted HMGB1 translocation from the nuclei to the cytoplasm, a process inhibited by the addition of the anti-HMGB1 mAb. These findings suggest that anti-HMGB1 mAb treatment not only inhibits HMGB1 translocation but also curtails inflammation in injured areas, thereby protecting the neural tissue. Thus, anti-HMGB1 mAb therapy could serve as a complementary therapy for an EDH before/after surgery.
摘要：
硬膜外和硬膜下血肿通常与创伤性脑损伤有关。虽然手术切除是这些血肿的主要干预措施，预防和减少创伤后癫痫等并发症也至关重要，这可能是由受损大脑区域的炎症反应引起的。在本研究中,我们观察到大鼠硬膜外血肿（EDH）下的受伤脑区高迁移率组box-1（HMGB1）降低，同时血浆HMGB1水平升高。抗HMGB1单克隆抗体疗法强烈抑制HMGB1释放和随后的血浆水平增加。此外，这种治疗抑制了炎症细胞因子和相关分子如白细胞介素-1β（IL-1β）的上调，肿瘤坏死因子-α（TNF-α），和诱导型一氧化氮合酶（iNOS）在受伤区域。我们使用SH-SY5Y进行的体外实验表明，血肿成分-凝血酶，血红素,亚铁离子促使HMGB1从细胞核转位到细胞质，通过添加抗HMGB1mAb抑制的过程。这些发现表明，抗HMGB1mAb治疗不仅抑制HMGB1易位，而且抑制损伤区域的炎症。从而保护神经组织。因此，抗HMGB1mAb治疗可作为EDH手术前后的补充治疗.
