中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (12): 2349-2352.doi: 10.4103/1673-5374.313014

• 综述:脑损伤修复保护与再生 •    下一篇

使用中性鞘磷脂酶抑制剂作为脑损伤的神经保护性治疗抑制细胞外囊泡通路

  

  • 出版日期:2021-12-15 发布日期:2021-05-13

Inhibition of extracellular vesicle pathway using neutral sphingomyelinase inhibitors as a neuroprotective treatment for brain injury

Asit Kumar*, Santosh Kumar    

  1. Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
  • Online:2021-12-15 Published:2021-05-13
  • Contact: Asit Kumar, PhD, akumar23@uthsc.edu or asitkumar14@gmail.com.
  • Supported by:
    This work was in part supported by the Plough Center for Sterile Drug Delivery Solution at the University of Tennessee Health Science Center (to SK).

PDF

366

摘要：

Neural Regen Res：中性鞘磷脂酶抑制剂: 创伤性脑损伤的神经保护策略

脑创伤后的急性和慢性后果可导致进行性继发性神经退行性改变和认知功能障碍。到目前为止，还没有有效的药物产品用于治疗减少脑损伤后的继发性损伤。细胞外囊泡在细胞间通讯中的作用而引起了科学界的广泛关注。细胞外囊泡不仅可以携带生物分子，而且可以作为药物载体。细胞外囊泡作为分子信息的载体，参与了机体的生理功能和免疫应答的调节。前期研究报道了中性鞘磷脂酶抑制剂调节中度控制性皮质撞击的小鼠神经毒性小胶质细胞激活和神经炎症的治疗潜力。中性鞘磷脂酶还减少了培养的小胶质细胞中一氧化氮和肿瘤坏死因子-α的产生，表明中性鞘磷脂酶可能在调节天然免疫过程中发挥作用。

来自美国田纳西大学健康科学中心的Asit Kumar团队认为基于近年的研究，细胞外囊泡似乎有望用于治疗干预。需要进一步研究以验证细胞外囊泡作为药物输送媒介的用途，尤其是靶向创伤性脑损伤。靶向中性鞘磷脂酶途径可能具有重要的治疗价值。但是，在对中性鞘磷脂酶进行药理学抑制或基因消融的转化有效性的背景下，有必要进行进一步的临床前研究，以阐明中性鞘磷脂酶抑制剂对创伤性脑损伤后脑功能恢复的作用。

文章在《中国神经再生研究（英文版）》杂志2021年 12月 12期发表。

https://orcid.org/0000-0003-1735-7033 (Asit Kumar)

https://orcid.org/0000-0001-7846-5674 (Santosh Kumar) 

Abstract: Traumatic brain injury is a sudden trauma or blow on the head, and severe traumatic brain injury is a major cause of death and disability worldwide. The acute and chronic consequences following traumatic brain injury can lead to progressive secondary neurodegenerative changes and cognitive dysfunction. To date, there is no effective pharmaceutical products for the treatment to reduce secondary damage after brain injury. The discovery of extracellular vesicles has attracted considerable scientific attention due to their role in cell-to-cell communication. Extracellular vesicles have shown their potential to carry not only biological molecules but also as a drug delivery vehicle. As a carrier of molecular information, extracellular vesicles have been involved in physiological functions as well as in the modulation of immune responses. Here, we aim to provide new insights into the contrasting role of extracellular vesicles in the propagation of inflammatory responses after brain injury. As a carrier of pro-inflammatory molecules, their role as functional mediators in the pathophysiology of brain injury is discussed, addressing the inhibition of the extracellular vesicle pathway as an anti-inflammatory or neuroprotective approach to improve the outcome of both acute and chronic inflammation following brain injury. Here, we summarize therapeutic strategies to diminish the risk the neurodegeneration post brain injury and propose that neutral sphingomyelinase inhibitors could be used as potentially useful therapeutic agents for the treatment of brain injury associated neuroinflammation.

Key words: brain injury, ceramide, extracellular vesicles, microglia, neuroinflammation, neuroprotection, neutral sphingomyelinase