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Extracellular Vesicles: Therapeutic Potential in Central Nervous System Trauma by Regulating Cell Death

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Abstract

CNS (central nervous system) trauma, which is classified as SCI (spinal cord injury) and TBI (traumatic brain injury), is gradually becoming a major cause of accidental death and disability worldwide. Many previous studies have verified that the pathophysiological mechanism underlying cell death and the subsequent neuroinflammation caused by cell death are pivotal factors in the progression of CNS trauma. Simultaneously, EVs (extracellular vesicles), membrane-enclosed particles produced by almost all cell types, have been proven to mediate cell-to-cell communication, and cell death involves complex interactions among molecules. EVs have also been proven to be effective carriers of loaded bioactive components to areas of CNS trauma. Therefore, EVs are promising therapeutic targets to cure CNS trauma. However, the link between EVs and various types of cell death in the context of CNS trauma remains unknown. Therefore, in this review, we summarize the mechanism underlying EV effects, the relationship between EVs and cell death and the pathophysiology underlying EV effects on the CNS trauma based on information in published papers. In addition, we discuss the prospects of applying EVs to the CNS as feasible therapeutic strategies for CNS trauma in the future.

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Abbreviations

ATG:

Autophagy-related protein

BBB:

Blood–brain barrier

BMDM:

Bone morrow-derived macrophage

CNS:

Central nervous system;

CSF:

Cerebrospinal fluid

DAMPs:

Damage-associated molecular patterns

ERK:

Extracellular signal-regulated kinase

ESCRT:

Endosomal sorting complexes required for transport

EVs:

Extracellular vesicles

GTPase:

Rab guanosine triphosphatase

ILVs:

Intraluminal vesicles

lncRNA:

Long noncoding RNA

MLKL:

Mixed lineage kinase domain-like

MREs:

MicroRNA response elements

MSC:

Mesenchymal stem cell

MVBs:

Multivesicular bodies

MVs:

Microvesicles

NGF:

Nerve growth factor

NLRP:

NOD-like receptor protein

NSC:

Neural stem cell

OGD:

Oxygen-glucose deprivation

PLD:

Phospholipase D

PS:

Phosphatidylserine

RIPK1:

Receptor-interacting protein kinase 1

RIPK3:

Receptor-interacting protein kinase 3

ROS:

Reactive oxygen species

SCI:

Spinal cord injury

SOCS6:

Cytokine signalling 6

TBI:

Traumatic brain injury

UTR:

3′ Untranslated region

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Acknowledgements

Figures 1–3 were illustrated by using Figdraw (www.figdraw.com).

Funding

This work was funded by grants from the National Natural Science Foundation of China (No. 82072192 to Kailiang Zhou); Wenzhou Science and Technology Bureau Foundation (No. Y20210438 to Kailiang Zhou); Public Welfare Technology Application Research Project of Zhejiang Province (LGF20H150003 to Kailiang Zhou); and Zhejiang Provincial Natural Science Foundation (No. LY17H060009 to Wenfei Ni).

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  1. Yituo Chen, Haojie Zhang and Xinli Hu are co-first authors who equally contributed to this manuscript.

Authors and Affiliations

  1. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, China

    Yituo Chen, Haojie Zhang, Wanta Cai, Liting Jiang, Xiangyang Wang, Wenfei Ni & Kailiang Zhou

  2. Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, 325027, China

    Yituo Chen, Haojie Zhang, Wanta Cai, Liting Jiang, Xiangyang Wang, Wenfei Ni & Kailiang Zhou

  3. Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China

    Xinli Hu

  4. Department of Orthopedics, Huzhou Central Hospital, Huzhou, 313099, China

    Yongli Wang

  5. Department of Orthopedics, Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Huzhou, 313099, China

    Yongli Wang

  6. The Institute of Life Sciences, Wenzhou University, Wenzhou, 325035, China

    Yanqing Wu

  7. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 West Xueyuan Road, Wenzhou, Zhejiang, 325000, China

    Wenfei Ni & Kailiang Zhou

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Yituo Chen, Haojie Zhang and Xinli Hu searched and reviewed literature and drafted manuscript and revision; Wanta Cai and Liting Jiang discussed and revised the manuscript; Yongli Wang, Yanqing Wu and Xiangyang Wang provided critical comments. Kailiang Zhou and Wenfei Ni designed and formulated the review theme and revised and finalized the manuscript.

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Chen, Y., Zhang, H., Hu, X. et al. Extracellular Vesicles: Therapeutic Potential in Central Nervous System Trauma by Regulating Cell Death. Mol Neurobiol 60, 6789–6813 (2023). https://doi.org/10.1007/s12035-023-03501-w

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