Interleukin-1β impedes oligodendrocyte progenitor cell recruitment and white matter repair following chronic cerebral hypoperfusion

2017 ◽  
Vol 60 ◽  
pp. 93-105 ◽  
Author(s):  
Yiting Zhou ◽  
Jing Zhang ◽  
Lu Wang ◽  
Ying Chen ◽  
Yushan Wan ◽  
...  
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 ◽  
...  

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.


2021 ◽  
Author(s):  
Zhaoyan Wang ◽  
Leping Zhang ◽  
Yinxiang Yang ◽  
Qian Wang ◽  
Suqing Qu ◽  
...  

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.


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 ◽  
...  

ASN NEURO ◽  
2010 ◽  
Vol 2 (1) ◽  
pp. AN20090033 ◽  
Author(s):  
Maria Vittoria Simonini ◽  
Paul E Polak ◽  
Anne I Boullerne ◽  
Jeffrey M Peters ◽  
Jill C Richardson ◽  
...  

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