Abstract
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.
Highlights
Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide
We found that exosomes derived from bone mesenchymal stem cells (BMSCs) could regulate the activation of different phenotypes microglia/macrophage cells in mice after TBI, which could be a potential mechanism of the functional recovery and neuroinflammation and apoptosis inhibition in the early stage induced by BMSC-exosomes
We demonstrated that the early systemic administration of BMSCs-exosomes showed promising therapeutic effects at early stages of TBI
Summary
Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. The therapy of TBI remains a challenge for scientists and clinicians. Post-TBI MSCs therapy has received enormous attention in recent times, with various animal studies reporting neurological functional recovery after treatment and even with some studies already translated in the clinical setting (Zhang et al, 2008; Zhang H. et al, 2017; Cox et al, 2011). In as much as MSCs are considered to have brain tissue repair properties, the underlying mechanism for their action remains unclear. Some studies have discovered that the major mechanism of MSCrelated tissue repair and function recovery was more likely due to their exosome-induced paracrine functions, not as a result of cell replacement (Li and Chopp, 2009; Lai et al, 2011)
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