Improvement by Human Oligodendrocyte Progenitor Cells of Neurobehavioral Disorders in an Experimental Model of Neonatal Periventricular Leukomalacia

Kim, Taekyun; Park, Dongsun; Ban, Young-Hwan; Cha, Yeseul; An, Eun Suk; Choi, Jieun; Choi, Ehn‐Kyoung; Kim, Yun-Bae

doi:10.1177/0963689718781330

Cited by 28 publications

(22 citation statements)

References 54 publications

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“…Another studied approach to ameliorate PVL was to transplant human oligodendrocyte progenitors. The results indicate that the transplanted cells restored neurobehavioral functions by preventing axonal demyelination and that human oligodendrocyte progenitor cells could be a suitable candidate for cell therapy of PVL (Kim T. K. et al, 2018).…”

Section: Periventricular Leukomalaciamentioning

confidence: 86%

Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells

Kirdajová

Kriška

Tureckova

et al. 2020

Front. Cell. Neurosci.

276

150

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A plethora of neurological disorders shares a final common deadly pathway known as excitotoxicity. Among these disorders, ischemic injury is a prominent cause of death and disability worldwide. Brain ischemia stems from cardiac arrest or stroke, both responsible for insufficient blood supply to the brain parenchyma. Glucose and oxygen deficiency disrupts oxidative phosphorylation, which results in energy depletion and ionic imbalance, followed by cell membrane depolarization, calcium (Ca 2+ ) overload, and extracellular accumulation of excitatory amino acid glutamate. If tight physiological regulation fails to clear the surplus of this neurotransmitter, subsequent prolonged activation of glutamate receptors forms a vicious circle between elevated concentrations of intracellular Ca 2+ ions and aberrant glutamate release, aggravating the effect of this ischemic pathway. The activation of downstream Ca 2+ -dependent enzymes has a catastrophic impact on nervous tissue leading to cell death, accompanied by the formation of free radicals, edema, and inflammation. After decades of "neuron-centric" approaches, recent research has also finally shed some light on the role of glial cells in neurological diseases. It is becoming more and more evident that neurons and glia depend on each other. Neuronal cells, astrocytes, microglia, NG2 glia, and oligodendrocytes all have their roles in what is known as glutamate excitotoxicity. However, who is the main contributor to the ischemic pathway, and who is the unsuspecting victim? In this review article, we summarize the so-far-revealed roles of cells in the central nervous system, with particular attention to glial cells in ischemiainduced glutamate excitotoxicity, its origins, and consequences.

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Section: Periventricular Leukomalaciamentioning

confidence: 86%

Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells

Kirdajová

Kriška

Tureckova

et al. 2020

Front. Cell. Neurosci.

276

150

View full text Add to dashboard Cite

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“…Studies show that nervous system development in SD rats at postnatal 2–5 days is equivalent to that in human preterm infants at 23–32 weeks of gestation [ 42 ]. Current studies using neonatal animal WMI models have employed electrocoagulation of the right common carotid artery in P3 SD rats after hypoxia to discover new therapeutic strategies [ 43 ]. Recent evidence suggests that ZJU-37 plays an important role in cell death processes and inhibiting inflammatory responses but does not induce apoptosis.…”

Section: Discussionmentioning

confidence: 99%

A novel RIP1/RIP3 dual inhibitor promoted OPC survival and myelination in a rat neonatal white matter injury model with hOPC graft

et al. 2021

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Background The dual inhibitors of receptor interacting protein kinase-1 and -3 (RIP1 and RIP3) play an important role in cell death processes and inflammatory responses. White matter injury (WMI), a leading cause of neurodevelopmental disabilities in preterm infants, which is characterized by extensive myelination disturbances and demyelination. Neuroinflammation, leads to the loss and differentiation-inhibition of oligodendrocyte precursor cells (OPCs), represents a major barrier to myelin repair. Whether the novel RIP1/RIP3 dual inhibitor ZJU-37 can promote transplanted OPCs derived from human neural stem cells (hOPCs) survival, differentiation and myelination remains unclear. In this study, we investigated the effect of ZJU-37 on myelination and neurobehavioral function in a neonatal rat WMI model induced by hypoxia and ischemia. Methods In vivo, P3 rat pups were subjected to right common carotid artery ligation and hypoxia, and then treated with ZJU-37 or/and hOPCs, then OPCs apoptosis, myelination, glial cell and NLRP3 inflammasome activation together with cognitive outcome were evaluated at 12 weeks after transplantation. In vitro, the effect of ZJU-37 on NLRP3 inflammasome activation in astrocytes induced by oxygen–glucose deprivation (OGD) were examined by western blot and immunofluorescence. The effect of ZJU-37 on OPCs apoptosis induced by the conditioned medium from OGD-injured astrocytes (OGD-astrocyte-CM) was analyzed by flow cytometry and immunofluorescence. Results ZJU-37 combined with hOPCs more effectively decreased OPC apoptosis, promoted myelination in the corpus callosum and improved behavioral function compared to ZJU-37 or hOPCs treatment. In addition, the activation of glial cells and NLRP3 inflammasome was reduced by ZJU-37 or/and hOPCs treatment in the neonatal rat WMI model. In vitro, it was also confirmed that ZJU-37 can suppress NLRP3 inflammasome activation in astrocytes induced by OGD. Not only that, the OGD-astrocyte-CM treated with ZJU-37 obviously attenuated OPC apoptosis and dysdifferentiation caused by the OGD-astrocyte-CM. Conclusions The novel RIP1/RIP3 dual inhibitor ZJU-37 may promote OPC survival, differentiation and myelination by inhibiting NLRP3 inflammasome activation in a neonatal rat model of WMI with hOPC graft.

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“…Studies show that nervous system development in SD rats at postnatal 2-5 days is equivalent to that in human preterm infants at 23-32 weeks of gestation [42]. Current studies using neonatal animal WMI models have employed electrocoagulation of the right common carotid artery in P3 SD rats after hypoxia to discover new therapeutic strategies [43]. Recent evidence suggests that ZJU-37 plays an important role in inhibiting in ammation and cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

ZJU-37 Promoted OPC Survival and Myelination in a Rat Neonatal White Matter Injury Model With hOPC Graft 

Zhang

Guan

Shi

et al. 2021

Preprint

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Background: Recent evidence suggests that ZJU-37 plays an important role in inhibiting inflammation and cell apoptosis. White matter injury (WMI), a leading cause of neurodevelopmental disabilities in preterm infants, which is characterized by extensive myelination disturbances and demyelination. Neuroinflammation, leads to the loss and differentiation-inhibition of oligodendrocyte precursor cells (OPCs), represents a major barrier to myelin repair. Whether ZJU-37 can promote transplanted OPCs derived from human neural stem cells (hOPCs) survival, differentiation and myelination remains unclear. In this study, we investigated the effect of ZJU-37 on myelination and neurobehavioral function in a neonatal rat WMI model induced by hypoxia and ischemia. Methods: In vivo, P3 rat pups were subjected to right common carotid artery ligation and hypoxia, and then treated with ZJU-37 or/and hOPCs, and OPCs apoptosis, myelination, glial cell and NLRP3 inflammasome activation together with cognitive outcome were evaluated at 12 weeks after transplantation. In vitro, the effect of ZJU-37 on NLRP3 inflammasome activation in astrocyte induced by oxygen-glucose deprivation (OGD) were examined by western blot and immunofluorescence. The effect of ZJU-37 on OPCs apoptosis induced by the conditioned medium from OGD-astrocyte was analyzed by flow cytometry and immunofluorescence. Results: ZJU-37 combined with hOPCs more effectively decreased OPC apoptosis, promoted myelination in the corpus callosum and improved behavioral function compared to ZJU-37 or OPCs treatment. In addition, the activation of glial cells and NLRP3 inflammasome was reduced by ZJU-37 or/and OPCs treatment in the neonatal rat WMI model. In vitro, it was also confirmed that ZJU-37 can suppress NLRP3 inflammasome activation in astrocytes induced by OGD. Not only that, the conditioned medium from OGD-injured astrocytes (OGD-astrocyte-CM) treated with ZJU-37 obviously attenuated OPC apoptosis and dysdifferentiation caused by the OGD-astrocyte-CM.Conclusions: ZJU-37 may promote OPC survival, differentiation and myelination by inhibiting NLRP3 inflammasome activation in a neonatal rat model of WMI with hOPC graft.

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Improvement by Human Oligodendrocyte Progenitor Cells of Neurobehavioral Disorders in an Experimental Model of Neonatal Periventricular Leukomalacia

Cited by 28 publications

References 54 publications

Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells

Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells

A novel RIP1/RIP3 dual inhibitor promoted OPC survival and myelination in a rat neonatal white matter injury model with hOPC graft

ZJU-37 Promoted OPC Survival and Myelination in a Rat Neonatal White Matter Injury Model With hOPC Graft

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Improvement by Human Oligodendrocyte Progenitor Cells of Neurobehavioral Disorders in an Experimental Model of Neonatal Periventricular Leukomalacia

Cited by 28 publications

References 54 publications

Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells

Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells

A novel RIP1/RIP3 dual inhibitor promoted OPC survival and myelination in a rat neonatal white matter injury model with hOPC graft

ZJU-37 Promoted OPC&nbsp;Survival and Myelination in a Rat Neonatal White Matter Injury Model With hOPC&nbsp;Graft&nbsp;

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ZJU-37 Promoted OPC Survival and Myelination in a Rat Neonatal White Matter Injury Model With hOPC Graft