中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (10): 2006-2007.doi: 10.4103/1673-5374.308092

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

高迁移率族box-1蛋白作为围产期缺氧缺血性脑损伤的治疗靶标

  

  • 出版日期:2021-10-15 发布日期:2021-03-19

High mobility group box-1 protein as a therapeutic target in perinatal hypoxic-ischemic brain injury

Kazuki Hatayama, Barbara S. Stonestreet*#br#   

  1. Department of Pediatrics, Women & Infants hospital of Rhode Island, The Alpert Medical School of Brown University, Providence, RI, USA
  • Online:2021-10-15 Published:2021-03-19
  • Contact: Barbara S. Stonestreet, MD, bstonestreet@wihri.org.
  • Supported by:
    This work was supported by NIH grants (No. 1R21NS095130, 1R21NS096525, 2R01HD057100, 2R44 NS084575).

摘要:

Neural Regen Res低温疗法联合抗HMGB1单克隆抗体治疗围产期缺氧缺血性脑损伤

 

围产期缺氧缺血性脑损伤是新生儿死亡和长期残疾的主要原因。有研究表明改善新生儿监护提高了有妊娠和分娩相关并发症的婴儿的存活率。尽管如此,许多存活下来的新生儿表现出神经系统异常,这种异常可能会持续一生。早期的神经保护策略有可能改善新生儿的神经系统预后和减轻发育迟缓。然而,低温是目前唯一批准的足月婴儿缺氧缺血性脑病的干预措施,仅在部分患儿中有保护作用。高迁移率族蛋白盒-1HMGB1)是一种典型的损伤相关分子模式蛋白,据报道与包括创伤性脑损伤、癫痫和中风在内的多种脑相关炎症性疾病有关。抗HMGB1疗法对治疗大脑炎症相关疾病的兴趣日益增加。然而,有关HMGB1在围产期缺氧缺血性相关脑损伤的病理学方面的资料还很少。来自美国的Barbara S. Stonestreet 博士及其团队讨论了HMGB1在围产期对缺氧缺血相关脑损伤的潜在作用,并探讨了HMGB1作为脑损伤治疗靶点的潜力。此外,这一观点强调了在围产期缺氧缺血性脑损伤中联合应用低温疗法和抗HMGB1单克隆抗体的潜力。

相关观点文章在《中国神经再生研究(英文版)》杂志202110 10  期发表。

https://orcid.org/0000-0002-1390-7715 (Kazuki Hatayama) 

Abstract: Perinatal hypoxic-ischemic (HI) brain injury is a leading cause of morbidity and long-standing disability in newborns (Millar et al., 2017). Improved neonatal intensive care has increased survival in infants with pregnancy and birth related complications.  Nonetheless, many surviving neonates exhibit neurological abnormalities that can persist throughout life (Millar et al., 2017). Early neuroprotective strategies have the potential to improve neurological outcomes and attenuate developmental delay in neonates. However, hypothermia is the only currently approved intervention for HI encephalopathy in full-term infants, which is only partially protective (Millar et al., 2017). Findings in preterm and full-term infants suggest that elevations in pro-inflammatory cytokines are important in the pathogenesis of HI-related brain injury (Millar et al., 2017). The high mobility group box-1 (HMGB1), a representative damage associated-molecular pattern (DAMP) protein, has been reported to be implicated in a variety of brain related inflammatory diseases including traumatic brain injury, epilepsy, and stroke (Nishibori et al., 2019). Anti-HMGB1 therapies have gained increasing interest to treat inflammation related disorders in the brain (Nishibori et al., 2019). However, there is a paucity of information regarding the pathology of HMGB1 in HI-related brain injury during the perinatal period. The current perspective discusses the potential contributions of HMGB1 to HI-related brain injury during the perinatal period and also addresses the potential of HMGB1 as a therapeutic target of the brain injury. Furthermore, this perspective emphasizes the potential for combinational therapeutics for hypothermia with anti-HMGB1 monoclonal antibodies (mAb) in perinatal HI brain injury.