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Front. Neurosci. | doi: 10.3389/fnins.2019.00014

Exosomes derived from mesenchymal stem cells ameliorate early inflammatory responses following traumatic brain injury

 Haoqi Ni1, 2,  su yang1, 2, Felix Siaw-Debrah1, 2,  zibin he1, 2,  Jiangnan Hu3,  jianjing yang1, 2, sishi pan1, 2, xiao lin1, 2, haotuo ye1, 2, zhu xu1, 2, fan wang1, 2,  Kunlin Jin1, 3, qichuan zhuge1, 2* and  lijie huang1, 2*
  • 1Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, First Affiliated Hospital, Wenzhou Medical University, China
  • 2Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, China
  • 3Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, United States

Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. Although treatment guidelines have been developed, no best treatment option or medicine for this condition exists. Recently, mesenchymal stem cells (MSCs)-derived exosomes have shown lots of promise for the treatment of brain disorders, with some results highlighting the neuroprotective effects through neurogenesis and angiogenesis after TBI. However, studies focusing on the role of exosomes in the early stages of neuroinflammation post-TBI are not sufficient. In this study, we investigated the role of bone mesenchymal stem cells (BMSCs)-exosomes in attenuating neuroinflammation at an early stage post-TBI and explored the potential regulatory neuroprotective mechanism. We administered 30 μg protein of BMSCs-exosomes or an equal volume of phosphate-buffered saline (PBS) via the retro-orbital route into C57BL/6 male mice 15 min after controlled cortical impact (CCI)-induced TBI. The results showed that the administration of BMSCs-exosomes reduced the lesion size and improved the neurobehavioral performance assessed by modified Neurological Severity Score (mNSS) and rotarod test. In addition, BMSCs-exosomes inhibited the expression of proapoptosis protein Bcl-2-associated X protein (BAX) and proinflammation cytokines, tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β, while enhancing the expression of the anti-apoptosis protein B-cell lymphoma 2 (BCL-2). Furthermore, BMSCs-exosomes modulated microglia/macrophage polarization by downregulating the expression of inducible nitric oxide synthase (INOS) and upregulating the expression of clusters of differentiation 206 (CD206) and arginase-1 (Arg1). In summary, our result shows that BMSCs-exosomes serve a neuroprotective function by inhibiting early neuroinflammation in TBI mice through modulating the polarization of microglia/macrophages. Further research into this may serve as a potential therapeutic strategy for the future treatment of TBI.

Keywords: Traumatic Brain Injury, Mesenchymal Stem Cells, Exosomes, Neuroprotection, Microglia/macrophage, Inflammation

Received: 28 Jun 2018; Accepted: 08 Jan 2019.

Edited by:

Mark P. Burns, Georgetown University, United States

Reviewed by:

David J. Loane, School of Medicine, University of Maryland, United States
Ye Xiong, Henry Ford Health System, United States  

Copyright: © 2019 Ni, yang, Siaw-Debrah, he, Hu, yang, pan, lin, ye, xu, wang, Jin, zhuge and huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. qichuan zhuge, Wenzhou Medical University, Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, First Affiliated Hospital, Wenzhou, 325000, China, zhugeqichuan@vip.163.com
MD, PhD. lijie huang, Wenzhou Medical University, Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, First Affiliated Hospital, Wenzhou, 325000, China, lijiehuangwy@163.com