Oligodendrocyte precursor cell transplantation promotes angiogenesis and remyelination via Wnt/β-catenin pathway in a mouse model of middle cerebral artery occlusion

2021 ◽  
pp. 0271678X2110653
Author(s):  
Li-Ping Wang ◽  
Jiaji Pan ◽  
Yongfang Li ◽  
Jieli Geng ◽  
Chang Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Cell Transplantation ◽  
Artery Occlusion ◽  
Precursor Cells ◽  
Precursor Cell ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor Cell ◽  
Oligodendrocyte Precursor ◽  
Cerebral Artery Occlusion

White matter injury is a critical pathological characteristic during ischemic stroke. Oligodendrocyte precursor cells participate in white matter repairing and remodeling during ischemic brain injury. Since oligodendrocyte precursor cells could promote Wnt-dependent angiogenesis and migrate along vasculature for the myelination during the development in the central nervous system, we explore whether exogenous oligodendrocyte precursor cell transplantation promotes angiogenesis and remyelination after middle cerebral artery occlusion in mice. Here, oligodendrocyte precursor cell transplantation improved motor and cognitive function, and alleviated brain atrophy. Furthermore, oligodendrocyte precursor cell transplantation promoted functional angiogenesis, and increased myelin basic protein expression after ischemic stroke. The further study suggested that white matter repairing after oligodendrocyte precursor cell transplantation depended on angiogenesis induced by Wnt/β-catenin signal pathway. Our results demonstrated a novel pathway that Wnt7a from oligodendrocyte precursor cells acting on endothelial β-catenin promoted angiogenesis and improved neurobehavioral outcomes, which facilitated white matter repair and remodeling during ischemic stroke.

scholarly journals Oligodendrocyte precursor cells transplantation protects blood–brain barrier in a mouse model of brain ischemia via Wnt/β-catenin signaling

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Liping Wang ◽  
Jieli Geng ◽  
Meijie Qu ◽  
Fang Yuan ◽  
Yuyang Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Precursor Cells ◽  
Precursor Cell ◽  
Brain Barrier ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor Cell ◽  
Blood Brain ◽  
Oligodendrocyte Precursor ◽  
Blood Brain Barrier Integrity

AbstractBlood–brain barrier damage is a critical pathological feature of ischemic stroke. Oligodendrocyte precursor cells are involved in maintaining blood–brain barrier integrity during the development. However, whether oligodendrocyte precursor cell could sustain blood–brain barrier permeability during ischemic brain injury is unknown. Here, we investigate whether oligodendrocyte precursor cell transplantation protects blood–brain barrier integrity and promotes ischemic stroke recovery. Adult male ICR mice (n = 68) underwent 90 min transient middle cerebral artery occlusion. After ischemic assault, these mice received stereotactic injection of oligodendrocyte precursor cells (6 × 105). Oligodendrocyte precursor cells transplantation alleviated edema and infarct volume, and promoted neurological recovery after ischemic stroke. Oligodendrocyte precursor cells reduced blood–brain barrier leakage via increasing claudin-5, occludin and β-catenin expression. Administration of β-catenin inhibitor blocked the beneficial effects of oligodendrocyte precursor cells. Wnt7a protein treatment increased β-catenin and claudin-5 expression in endothelial cells after oxygen–glucose deprivation, which was similar to the results of the conditioned medium treatment of oligodendrocyte precursor cells on endothelial cells. We demonstrated that oligodendrocyte precursor cells transplantation protected blood–brain barrier in the acute phase of ischemic stroke via activating Wnt/β-catenin pathway. Our results indicated that oligodendrocyte precursor cells transplantation was a novel approach to the ischemic stroke therapy.

Ginkgolide B promotes oligodendrocyte precursor cell differentiation and survival via Akt/CREB/bcl-2 signaling pathway after white matter lesion

2021 ◽  
pp. 153537022198995
Author(s):  
Jian Huang ◽  
Jun Yang ◽  
Xingju Zou ◽  
Shilun Zuo ◽  
Jing Wang ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Lesion ◽  
Neuroprotective Effect ◽  
Precursor Cell ◽  
Cerebral Hypoperfusion ◽  
Ginkgolide B ◽  
Oligodendrocyte Precursor Cell ◽  
Learning Abilities ◽  
Phosphorylated Akt ◽  
Oligodendrocyte Precursor

White matter lesion (WML) is caused by chronic cerebral hypoperfusion, which are usually associated with cognitive impairment. Evidence from recent studies has shown that ginkgolide B has a neuroprotective effect that could be beneficial for the treatment of ischemia; however, it is not clear whether ginkgolide B has a protective effect on WML. Our data show that ginkgolide B can promote the differentiation of oligodendrocyte precursor cell (OPC) into oligodendrocytes and promote oligodendrocyte survival following a WML. Ginkgolide B (5, 10, 20 mg/kg) or saline is administered intraperitoneally every day after WML. After 4 weeks, the data of Morris water maze suggested that rats’ memory and learning abilities were impaired, and the administration of ginkgolide B enhanced behavioral achievement. Also, treatment with ginkgolide B significantly attenuated this loss of myelin. Our result suggests that ginkgolide B promotes the differentiation of OPC into oligodendrocytes. We also found that ginkgolide B ameliorates oligodendrocytes apoptosis. Furthermore, ginkgolide B enhanced the expression of phosphorylated Akt and CREB. In conclusion, our data firstly show that ginkgolide B promotes oligodendrocyte genesis and oligodendrocyte myelin following a WML, possibly involving the Akt and CREB pathways.

Abstract TMP30: M2 Microglia Derived Exosomes Promote White Matter Repair and Long-Term Functional Recovery After Focal Cerebral Ischemia in Mice

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yongfang Li ◽  
Longlong Luo ◽  
Zhijun Zhang ◽  
Yaohui Tang ◽  
Guo-Yuan Yang
Keyword(s):  
White Matter ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor Cell ◽  
M2 Microglia ◽  
Oligodendrocyte Precursor ◽  
White Matter Repair ◽  
Exosomal Mirna

Objectives: White matter injury aggravates neurological and cognitive impairment in experimental ischemic stroke. M2 microglia promote oligodendrocyte precursor cells survival and differentiation, and further enhance white matter repair. However, the molecular mechanism is unclear. Here, we explored the effect and mechanism of M2 microglia-derived exosomes on white matter repair after focal cerebral ischemia in mice. Methods: Microglia BV2 cells were polarized to M2 phenotype by IL-4 stimulation. Exosomes were isolated from M2 microglia (M2-Exo) and unstimulated microglia as a control (M0-Exo). M2-Exo and M0-Exo (100 μg) were intravenously injected after 90-minute middle cerebral artery occlusion in mice (n=72). Brain atrophy volume and neuro behavioral outcomes were examined in 28 days following focal cerebral ischemia. Oligodendrocyte precursor cells survival, differentiation and white matter integrity were evaluated. Exosomal miRNA and target gene were further examined to explore molecular mechanism. Results: M2-Exo treatment promoted sensorimotor and memory function recovery ( p <0.05), and further reduced brain atrophy compared to the M0-Exo control group ( p <0.001). Immunostaining showed that M2-Exo increased the number of BrdU + /Pdgfr-α + and BrdU + /adenomatous polyposis coli + cells, enhanced myelin basic protein fluorescence-intensity compared to the control ( p <0.05). M2-Exo increased oligodendrocyte precursor cell survival under OGD in vi tro , ( p <0.05) and differentiation ( p <0.05). Exosomal miRNA sequencing and PCR identified that miR-23a-5p was enriched in M2-Exo. Conclusion: Our results showed that M2-Exo treatment enhanced oligodendrocyte precursor cell survival and differentiation, further promoted white matter repair and long-term functional recovery, suggesting that M2-Exo is a novel therapeutic strategy for the white matter repair after ischemic brain injury.

Regulation of L-type Ca++ currents and process morphology in white matter oligodendrocyte precursor cells by golli-myelin proteins

Glia ◽  
2010 ◽  
Vol 58 (11) ◽  
pp. 1292-1303 ◽  
Author(s):  
Daniel Fulton ◽  
Pablo M. Paez ◽  
Robin Fisher ◽  
Vance Handley ◽  
Christopher S. Colwell ◽  
...  
Keyword(s):  
White Matter ◽  
Precursor Cells ◽  
Myelin Proteins ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor ◽  
Ca Currents

scholarly journals Effect of Methylene Blue on White Matter Injury after Ischemic Stroke

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Quancheng Cheng ◽  
Xuhao Chen ◽  
Jiayi Ma ◽  
Xingyuan Jiang ◽  
Jiahui Chen ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Ischemic Stroke ◽  
White Matter ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
White Matter Injury ◽  
Behavioral Deficits ◽  
Cerebral Artery Occlusion

Methylene blue, the FDA-grandfathered drug was proved to be neuroprotective in ischemic stroke in rat. However, the mechanism of the protective effect was unknown. In this study, we used different animal models to investigate the effect of MB administration given within and beyond the therapeutic time window on behavioral deficits and infarct volume and related mechanism about the white matter protection. Middle cerebral artery occlusion and reperfusion (MCAO) and photothrombotic middle cerebral artery occlusion (PT-MCAO) models were used. Behavioral deficits and infarct volume were measured by foot fault test, Garcia neurological score, and TTC staining. Black gold staining and western blot were used to evaluate the brain white matter injury. We found that intraperitoneal administration of MB immediately or 24 h after the MCAO or PT-MCAO surgery reduced infarct volume, improved the neurological deficits, and reduced the white matter injury via myelin basic protein (BMP) protection. These findings suggested that MB relieved the white matter injury besides neuronal protection and has potential therapeutic effects on ischemic stroke.

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