Extracellular vesicles derived from bone marrow mesenchymal stem cells enhance myelin maintenance after cortical injury in aged rhesus monkeys

Go, Veronica; Sarikaya, Deniz; Zhou, Yuxin; Bowley, Bethany; Pessina, Monica A.; Rosene, Douglas L.; Zhang, Zheng Gang; Chopp, Michael; Finklestein, Seth P.; Medalla, Maria; Buller, Benjamin; Moore, Tara

doi:10.1016/j.expneurol.2020.113540

Cited by 21 publications

(25 citation statements)

References 68 publications

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“…White matter is involved in motor function, and white matter injury is considered to be one of the main pathological changes of multiple nervous system injuries ( Bacmeister et al, 2020 ). Moreover, with the continuous in-depth study of white matter in complex brain functions such as learning, memory and emotion, reducing white matter injury become a potential target to further promote the functional recovery after nervous system damage ( Xin et al, 2020 ; Go et al, 2021 ; Luo et al, 2021 ). Although a previous study has reported that 6-Gingerol can alleviate demyelination induced by multiple sclerosis, the specific mechanism of the oligodendrocytes involved in myelin injury has not been explored ( Han et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…At present, mild hypothermia treatment of HIE is effective to some extent, but the therapeutic time window is too narrow to allow a timely start. (Gluckman et al, 2005;Graham et al, 2008;Edwards et al, 2010). Therefore, there is an urgent need to explore new effective therapies to minimize brain injury and neurological sequelae of HIE in neonates.…”

Section: Introductionmentioning

confidence: 99%

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6-Gingerol Alleviates Neonatal Hypoxic-Ischemic Cerebral and White Matter Injury and Contributes to Functional Recovery

Zhao

Yao

et al. 2021

Front. Pharmacol.

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Hypoxic-ischemic encephalopathy (HIE) is one main cause of neonatal death and disability, causing substantial injury to white and gray matter, which can lead to severe neurobehavioral dysfunction, including intellectual disability and dyskinesia. Inflammation, nerve cell death, and white matter injury are important factors in the pathological process of HIE. 6-Gingerol is a ginger extract, which reduces inflammatory response and cell death. However, the role of 6-Gingerol in neonatal hypoxic-ischemic brain injury (HIBI) remains unknown. In this study, we constructed a mouse HIBI model and analyzed the protective effect of 6-Gingerol on HIBI by using behavioral tests, histological staining, qPCR and western blot. Here, we found that 6-Gingerol treatment could alleviate HIBI and improve short-term reflex performance, which is closely related to cell death and neuroinflammation. Additionally, 6-Gingerol reduced neuronal apoptosis, pro-inflammatory factor release, as well as microglial activation. Furthermore, 6-Gingerol significantly improved motor disability, which is associated with white matter damage. Thus, our results showed that 6-Gingerol could reduce the loss of myelin sheaths, alleviate cell death of oligodendrocytes, and stimulate the maturation of oligodendrocytes. In terms of mechanism, we found that 6-Gingerol decreased histone H3K27me3 levels, activated AKT pathway and inhibited the activation of ERK and NF-κB pathway at 3 days post-HIBI. Taken together, our data clearly indicate that 6-Gingerol plays a neuroprotective role against HIBI by epigenetic modification and regulation of AKT, ERK, and NF-κB pathways, inhibiting inflammatory responses and reducing cell death.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

6-Gingerol Alleviates Neonatal Hypoxic-Ischemic Cerebral and White Matter Injury and Contributes to Functional Recovery

Zhao

Yao

et al. 2021

Front. Pharmacol.

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“…Treatment with these exosomes results in a higher count of oligodendrocyte progenitor cells (OPCs), mature oligodendrocytes, and myelinated axons [ 59 , 60 ], alluding to their effects on endogenous stem cells [ 64 ]. Furthermore, MSC-derived exosomes can strengthen endogenous repair mechanisms that specifically target white matter injury [ 65 ]. Additionally, bone marrow-derived mesenchymal stem cell (BM-MSCs) administration results in a heightened division of endogenous NPCs in the SVZ [ 61 , 66 , 67 , 68 ].…”

Section: Introductionmentioning

confidence: 99%

“…The brain exhibits innate repair mechanisms that target white matter damage. White matter injury induced by ischemic stroke generates significant injury to oligodendrocytes, axons, and myelin sheaths [ 65 , 145 ]. Stroke-induced white matter damage entails rapid myelin deterioration [ 145 , 146 , 147 ] and axonal loss in the ischemic infarct [ 148 ].…”

Section: Introductionmentioning

confidence: 99%

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Combination of Stem Cells and Rehabilitation Therapies for Ischemic Stroke

et al. 2021

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Stem cell transplantation with rehabilitation therapy presents an effective stroke treatment. Here, we discuss current breakthroughs in stem cell research along with rehabilitation strategies that may have a synergistic outcome when combined together after stroke. Indeed, stem cell transplantation offers a promising new approach and may add to current rehabilitation therapies. By reviewing the pathophysiology of stroke and the mechanisms by which stem cells and rehabilitation attenuate this inflammatory process, we hypothesize that a combined therapy will provide better functional outcomes for patients. Using current preclinical data, we explore the prominent types of stem cells, the existing theories for stem cell repair, rehabilitation treatments inside the brain, rehabilitation modalities outside the brain, and evidence pertaining to the benefits of combined therapy. In this review article, we assess the advantages and disadvantages of using stem cell transplantation with rehabilitation to mitigate the devastating effects of stroke.

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Involvement of extracellular vesicles in aging process and their beneficial effects in alleviating aging‐associated symptoms

Das

Kale

2021

Cell Biology International

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Extracellular vesicles derived from bone marrow mesenchymal stem cells enhance myelin maintenance after cortical injury in aged rhesus monkeys

Cited by 21 publications

References 68 publications

6-Gingerol Alleviates Neonatal Hypoxic-Ischemic Cerebral and White Matter Injury and Contributes to Functional Recovery

6-Gingerol Alleviates Neonatal Hypoxic-Ischemic Cerebral and White Matter Injury and Contributes to Functional Recovery

Combination of Stem Cells and Rehabilitation Therapies for Ischemic Stroke

Involvement of extracellular vesicles in aging process and their beneficial effects in alleviating aging‐associated symptoms

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