scholarly journals Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury

2015 ◽  
Vol 36 (1) ◽  
pp. 187-198 ◽  
Author(s):  
Akihiro Shindo ◽  
Anna C Liang ◽  
Takakuni Maki ◽  
Nobukazu Miyamoto ◽  
Hidekazu Tomimoto ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Ischemia ◽  
Nerve Conduction ◽  
Neurovascular Unit ◽  
Cell Types ◽  
Subcortical White Matter ◽  
Experimental Models ◽  
White Matter Injury ◽  
Cerebral White Matter ◽  
Myelin Sheaths

Oligodendrocytes are one of the major cell types in cerebral white matter. Under normal conditions, they form myelin sheaths that encircle axons to support fast nerve conduction. Under conditions of cerebral ischemia, oligodendrocytes tend to die, resulting in white-matter dysfunction. Repair of white matter involves the ability of oligodendrocyte precursors to proliferate and mature. However, replacement of lost oligodendrocytes may not be the only mechanism for white-matter recovery. Emerging data now suggest that coordinated signaling between neural, glial, and vascular cells in the entire neurovascular unit may be required. In this mini-review, we discuss how oligodendrocyte lineage cells participate in signaling and crosstalk with other cell types to underlie function and recovery in various experimental models of subcortical white-matter injury.

Optimizing the Dose of Erythropoietin Required to Prevent Acute Ventilation-Induced Cerebral White Matter Injury in Preterm Lambs

2017 ◽  
Vol 39 (1-4) ◽  
pp. 298-309 ◽  
Author(s):  
Kyra Y.Y. Chan ◽  
Domenic A. LaRosa ◽  
Mary Tolcos ◽  
Anqi Li ◽  
Valerie A. Zahra ◽  
...  
Keyword(s):  
White Matter ◽  
Bolus Dose ◽  
Quantitative Polymerase Chain Reaction ◽  
Optimal Dose ◽  
Subcortical White Matter ◽  
White Matter Injury ◽  
Preterm Neonates ◽  
Cerebral White Matter ◽  
Mrna Levels ◽  
Protein Extravasation

Erythropoietin (EPO) is being trialed in preterm neonates for neuroprotection. We have recently demonstrated that a single high bolus dose (5,000 IU/kg) of recombinant human EPO amplified preterm lung and brain ventilation-induced injury. We aimed to determine the optimal dose of EPO to reduce ventilation-induced cerebral white matter inflammation and injury in preterm lambs. Lambs (0.85 gestation) were ventilated with an injurious strategy for 15 min followed by conventional ventilation for 105 min. Lambs were randomized to no treatment (VENT; n = 8) or received a bolus dose of EPO (EPREX®): 300 IU/kg (EPO 300; n = 5), 1,000 IU/kg (EPO 1,000; n = 5), or 3,000 IU/kg (EPO 3,000; n = 5). Physiological parameters were measured throughout the study. After 2 h, brains were collected for analysis; real-time quantitative polymerase chain reaction and immunohistochemistry were used to assess inflammation, cell death, and vascular leakage in the periventricular and subcortical white matter (PVWM; SCWM). Molecular and histological inflammatory indices in the PVWM were not different between groups. EPO 300 lambs had higher IL-6 (p = 0.006) and caspase-3 (p = 0.025) mRNA expression in the SCWM than VENT lambs. Blood-brain barrier (BBB) occludin mRNA levels were higher in EPO 3,000 lambs in the PVWM and SCWM than VENT lambs. The number of blood vessels with protein extravasation in the SCWM was lower in EPO 1,000 (p = 0.010) and EPO 3,000 (p = 0.025) lambs compared to VENT controls but not different between groups in the PVWM. Early administration of EPO at lower doses neither reduced nor exacerbated cerebral white matter inflammation or injury. 3,000 IU/kg EPO may provide neuroprotection by improving BBB integrity.

Cerebral white matter injury and damage to myelin sheath following whole-brain ischemia

2013 ◽  
Vol 1495 ◽  
pp. 11-17 ◽  
Author(s):  
Yingzhu Chen ◽  
Qiong Yi ◽  
Gang Liu ◽  
Xue Shen ◽  
Lihui Xuan ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Ischemia ◽  
Myelin Sheath ◽  
White Matter Injury ◽  
Cerebral White Matter ◽  
Whole Brain

scholarly journals COVID-19-Associated Cerebral White Matter Injury in a Newborn Infant With Afebrile Seizure

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Harun Yildiz ◽  
Erbu Yarci ◽  
Sefika Elmas Bozdemir ◽  
Nesrin Ozdinc Kizilay ◽  
Senay Mengi ◽  
...  
Keyword(s):  
White Matter ◽  
Newborn Infant ◽  
White Matter Injury ◽  
Cerebral White Matter ◽  
Afebrile Seizure

scholarly journals A Systematic Review of WNT Signaling in Endothelial Cell Oligodendrocyte Interactions: Potential Relevance to Cerebral Small Vessel Disease

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1545
Author(s):  
Narek Manukjan ◽  
Zubair Ahmed ◽  
Daniel Fulton ◽  
W. Matthijs Blankesteijn ◽  
Sébastien Foulquier
Keyword(s):  
White Matter ◽  
Small Vessel Disease ◽  
Clinical Manifestations ◽  
Cell Types ◽  
Cerebral Small Vessel Disease ◽  
White Matter Injury ◽  
Small Vessel ◽  
Limited Attention ◽  
Vessel Disease

Key pathological features of cerebral small vessel disease (cSVD) include impairment of the blood brain barrier (BBB) and the progression of white matter lesions (WMLs) amongst other structural lesions, leading to the clinical manifestations of cSVD. The function of endothelial cells (ECs) is of major importance to maintain a proper BBB. ECs interact with several cell types to provide structural and functional support to the brain. Oligodendrocytes (OLs) myelinate axons in the central nervous system and are crucial in sustaining the integrity of white matter. The interplay between ECs and OLs and their precursor cells (OPCs) has received limited attention yet seems of relevance for the study of BBB dysfunction and white matter injury in cSVD. Emerging evidence shows a crosstalk between ECs and OPCs/OLs, mediated by signaling through the Wingless and Int-1 (WNT)/β-catenin pathway. As the latter is involved in EC function (e.g., angiogenesis) and oligodendrogenesis, we reviewed the role of WNT/β-catenin signaling for both cell types and performed a systematic search to identify studies describing a WNT-mediated interplay between ECs and OPCs/OLs. Dysregulation of this interaction may limit remyelination of WMLs and render the BBB leaky, thereby initiating a vicious neuroinflammatory cycle. A better understanding of the role of this signaling pathway in EC–OL crosstalk is essential in understanding cSVD development.

scholarly journals Window of Opportunity of Cerebral Hypothermia for Postischemic White Matter Injury in the Near-Term Fetal Sheep

2004 ◽  
Vol 24 (8) ◽  
pp. 877-886 ◽  
Author(s):  
Vincent Roelfsema ◽  
Laura Bennet ◽  
Sherly George ◽  
David Wu ◽  
Jian Guan ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Ischemia ◽  
Caspase 3 ◽  
Basic Protein ◽  
White Matter Injury ◽  
Window Of Opportunity ◽  
Reactive Microglia ◽  
Fetal Sheep ◽  
Near Term ◽  
Protein Density

Postresuscitation cerebral hypothermia is consistently neuroprotective in experimental preparations; however, its effects on white matter injury are poorly understood. Using a model of reversible cerebral ischemia in unanesthetized near-term fetal sheep, we examined the effects of cerebral hypothermia (fetal extradural temperature reduced from 39.4±0.1°C to between 30 and 33°C), induced at different times after reperfusion and continued for 72 hours after ischemia, on injury in the parasagittal white matter 5 days after ischemia. Cooling started within 90 minutes of reperfusion was associated with a significant increase in bioactive oligodendrocytes in the intragyral white matter compared with sham cooling (41±20 vs 18±11 per field, P < 0.05), increased myelin basic protein density and reduced expression of activated caspase-3 (14±12 vs 91±51, P < 0.05). Reactive microglia were profoundly suppressed compared with sham cooling (4±6 vs 38±18 per field, P < 0.05) with no effect on numbers of astrocytes. When cooling was delayed until 5.5 hours after reperfusion there was no significant effect on loss of oligodendrocytes (24±12 per field). In conclusion, hypothermia can effectively protect white matter after ischemia, but only if initiated early after the insult. Protection was closely associated with reduced expression of both activated caspase-3 and of reactive microglia.

scholarly journals Combining Hypothermia and Oleuropein Subacutely Protects Subcortical White Matter in a Swine Model of Neonatal Hypoxic-Ischemic Encephalopathy

2020 ◽  
Author(s):  
Jennifer K Lee ◽  
Polan T Santos ◽  
May W Chen ◽  
Caitlin E O’Brien ◽  
Ewa Kulikowicz ◽  
...  
Keyword(s):  
White Matter ◽  
Motor Cortex ◽  
Corpus Callosum ◽  
Internal Capsule ◽  
Subcortical White Matter ◽  
White Matter Injury ◽  
Swine Model ◽  
Cortex Neuron ◽  
Motor Cortex Neuron ◽  
Ischemic Encephalopathy

Abstract Neonatal hypoxia-ischemia (HI) causes white matter injury that is not fully prevented by therapeutic hypothermia. Adjuvant treatments are needed. We compared myelination in different piglet white matter regions. We then tested whether oleuropein (OLE) improves neuroprotection in 2- to 4-day-old piglets randomized to undergo HI or sham procedure and OLE or vehicle administration beginning at 15 minutes. All groups received overnight hypothermia and rewarming. Injury in the subcortical white matter, corpus callosum, internal capsule, putamen, and motor cortex gray matter was assessed 1 day later. At baseline, piglets had greater subcortical myelination than in corpus callosum. Hypothermic HI piglets had scant injury in putamen and cerebral cortex. However, hypothermia alone did not prevent the loss of subcortical myelinating oligodendrocytes or the reduction in subcortical myelin density after HI. Combining OLE with hypothermia improved post-HI subcortical white matter protection by preserving myelinating oligodendrocytes, myelin density, and oligodendrocyte markers. Corpus callosum and internal capsule showed little HI injury after hypothermia, and OLE accordingly had minimal effect. OLE did not affect putamen or motor cortex neuron counts. Thus, OLE combined with hypothermia protected subcortical white matter after HI. As an adjuvant to hypothermia, OLE may subacutely improve regional white matter protection after HI.

scholarly journals Lipopolysaccharide-induced peroxisomal dysfunction exacerbates cerebral white matter injury: Attenuation by N-acetyl cysteine

2008 ◽  
Vol 210 (2) ◽  
pp. 560-576 ◽  
Author(s):  
Manjeet K. Paintlia ◽  
Ajaib S. Paintlia ◽  
Miguel A. Contreras ◽  
Inderjit Singh ◽  
Avtar K. Singh
Keyword(s):  
White Matter ◽  
White Matter Injury ◽  
Cerebral White Matter ◽  
Acetyl Cysteine

Neonatal nucleated red blood cells are a marker for infants at risk for cerebral white matter injury

2004 ◽  
Vol 191 (6) ◽  
pp. S81
Author(s):  
Anadir Silva ◽  
Randi Smith ◽  
Christoph Lehmann ◽  
Cynthia Holcroft ◽  
Ernest Graham
Keyword(s):  
At Risk ◽  
White Matter ◽  
Red Blood Cells ◽  
Blood Cells ◽  
White Matter Injury ◽  
Cerebral White Matter ◽  
Nucleated Red Blood Cells
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