Oligodendrocyte Progenitor Cell Proliferation and Fate after White Matter Stroke in Juvenile and Adult Mice

2018 ◽  
Vol 40 (5-6) ◽  
pp. 601-616 ◽  
Author(s):  
Andra L. Dingman ◽  
Krista M. Rodgers ◽  
Robert M. Dietz ◽  
Sean P. Hickey ◽  
Alexandra P. Frazier ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Cell Fate ◽  
Cellular Response ◽  
Progenitor Cell ◽  
Ischemic Injury ◽  
Oligodendrocyte Progenitor Cell ◽  
Oligodendrocyte Progenitor ◽  
Time Points ◽  
Adult Mice

The incidence of stroke in children is 2.4 per 100,000 person-years and results in long-term motor and cognitive disability. In ischemic stroke, white matter (WM) is frequently injured, but is relatively understudied compared to grey matter injury. Previous research suggests that the cellular response to WM ischemic injury is different at different ages. Little is known about whether WM repair mechanisms differ in children and adults. We utilized a model of focal ischemic WM injury to determine the oligodendrocyte (OL) response to focal WM ischemic injury in juvenile and adult mice. Methods: Juvenile (21–25 days of age) versus adult (2–3 months of age) mice underwent stereotaxic injection of the potent vasoconstrictor N5-(1-iminoethyhl)-L-ornithine (L-NIO) into the lateral corpus callosum (CC). Animals were sacrificed on postoperative day 3 (acute) or 21 (chronic). Cell birth-dating was performed acutely after WM stroke with 5-ethynyl-2-deoxyuridine (EdU) injected intraperitoneally. Immunohistochemistry was performed, as well as stereology, to measure injury volume. The acute oligodendrocyte progenitor cell (OPC) proliferation and the chronic OL cell fate were determined with immunohistochemistry. Compound action potentials were measured in the CC at acute and chronic time points. Results: Acutely WM injury volume was smaller in juveniles. There was significantly greater OPC proliferation in juvenile animals (acute) compared to adults, but newly born OLs did not survive and mature into myelinating cells at chronic time points. In addition, juveniles did not have improved histological or functional recovery when compared to adults. Protecting newly born OPCs is a potential therapeutic target in children with ischemic stroke.

scholarly journals Exogenous Oligodendrocyte Progenitor Cell Transplantation Results in Structural and Functional Recovery in a Preterm Infant Cerebral White Matter Injury Rat Model

2021 ◽  
Author(s):  
Zhaoyan Wang ◽  
Leping Zhang ◽  
Yinxiang Yang ◽  
Qian Wang ◽  
Suqing Qu ◽  
...  
Keyword(s):  
White Matter ◽  
Corpus Callosum ◽  
Preterm Infant ◽  
Preterm Infants ◽  
Rat Model ◽  
Progenitor Cell ◽  
White Matter Injury ◽  
Morris Water Maze Test ◽  
Oligodendrocyte Progenitor Cell ◽  
Oligodendrocyte Progenitor

Abstract BackgroundCerebral white matter injury (WMI) is the most common brain injury in preterm infants; it leads to motor and developmental deficits and is often accompanied by cognitive impairment. WMI is characterized by the loss of pre-myelinating oligodendrocytes. Regeneration therapies for preterm neonates with WMI are still in the preclinical phase, among which oligodendrocyte progenitor cell (OPC) transplantation is a promising approach. One promising approach for treating preterm infants is cell replacement therapy, in which lost cells are replaced by human OPCs (hOPCs) derived from human neural stem cells (hNSCs). MethodsIn this study, we developed a method to induce the differentiation of hNSCs into hOPCs. OLIG2+/NG2+/PDGFRα+/O4+ hOPCs were enriched and transplanted into the corpus callosum of a preterm infant WMI rat model. ResultsTransplanted hOPCs survived and migrated throughout the major white matter tracts. Morphological differentiation of transplanted hOPCs was observed. Histology and Magnetic resonance imaging (MRI) revealed lesioned structural repair. Electron microscopy revealed the re-myelination of the axons in the corpus callosum. The Morris water maze test revealed a recovery of cognitive function. ConclusionsOur study showed that transplantation of hOPCs derived from hNSCs is a viable therapeutic strategy for cerebral WMI. The results of our study contribute to the further development of cell therapeutic strategies.

scholarly journals Excitotoxic Mechanisms of Ischemic Injury in Myelinated White Matter

2007 ◽  
Vol 27 (9) ◽  
pp. 1540-1552 ◽  
Author(s):  
Selva Baltan Tekkök ◽  
ZuCheng Ye ◽  
Bruce R Ransom
Keyword(s):  
White Matter ◽  
High Performance ◽  
Glutamate Release ◽  
Glutamate Transporter ◽  
Ischemic Injury ◽  
Glucose Deprivation ◽  
Kainate Receptors ◽  
Adult Mice ◽  
Direct Exposure ◽  
Glutamate Receptor Agonist

Axonal injury and dysfunction in white matter (WM) are caused by many neurologic diseases including ischemia. We characterized ischemic injury and the role of glutamate-mediated excitotoxicity in a purely myelinated WM tract, the mouse optic nerve (MON). For the first time, excitotoxic WM injury was directly correlated with glutamate release. Oxygen and glucose deprivation (OGD) caused duration-dependent loss of axon function in optic nerves from young adult mice. Protection of axon function required blockade of both α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptors, or removal of extracellular Ca2+. Blockade of N-methyl-D-aspartate receptors did not preserve axon function. Curiously, even extended periods of direct exposure to glutamate or kainate or AMPA failed to induce axon dysfunction. Brief periods of OGD, however, caused glutamate receptor agonist exposure to become toxic, suggesting that ionic disruption enabled excitotoxic injury. Glutamate release, directly measured using quantitative high-performance liquid chromatography, occurred late during a 60-mins period of OGD and was due to reversal of the glutamate transporter. Brief periods of OGD (i.e., 15 mins) did not cause glutamate release and produced minimal injury. These results suggested that toxic glutamate accumulation during OGD followed the initial ionic changes mediating early loss of excitability. The onset of glutamate release was an important threshold event for irreversible ischemic injury. Regional differences appear to exist in the specific glutamate receptors that mediate WM ischemic injury. Therapy for ischemic WM injury must be designed accordingly.

scholarly journals Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

Cell Reports ◽  
2017 ◽  
Vol 20 (8) ◽  
pp. 1755-1764 ◽  
Author(s):  
Alerie Guzman De La Fuente ◽  
Simona Lange ◽  
Maria Elena Silva ◽  
Ginez A. Gonzalez ◽  
Herbert Tempfer ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Progenitor Cell ◽  
Oligodendrocyte Progenitor Cell ◽  
Oligodendrocyte Progenitor
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