Mesenchymal stem cells restore cortical rewiring after neonatal ischemia in mice

Velthoven, Cindy T. J. van; Looij, Yohan van de; Kavelaars, Annemieke; Zijlstra, Jitske; Bel, Frank van; Hüppi, Petra Susan; Sizonenko, Stéphane; Heijnen, Cobi J.

doi:10.1002/ana.23543

Cited by 62 publications

(55 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We have shown before that HI can induce a decline in lateral arborization of MBP-positive fibers in the ipsilateral cingulum, defined as an increase in fiber coherency demonstrated by a more linear MBP pattern [23]. Figure 3d and e show that HI did not result in a significant increase in MBP-positive fiber coherency (indicating no significant reduction in lateral arborization of MBP-positive fibers) within the cingulum at D10 postinsult compared to sham-operated littermates.…”

Section: Resultsmentioning

confidence: 84%

“…It is known that HI can induce changes in corpus callosum volume, which is associated with lateralizing motor deficits [22,23]. Therefore, we measured the thickness of the corpus callosum after HI and LPS+HI at the striatal level, both at the midline and in the contra- and ipsilateral hemisphere at D10 postinsult.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, arborization of the myelinated fibers in the cingulum was strongly reduced by LPS+HI. Axonal injury in this part of the brain has been shown to be involved in cognition, working-memory performance and motor function, for example [23,48,51,52]. …”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Development of Cerebral Gray and White Matter Injury and Cerebral Inflammation over Time after Inflammatory Perinatal Asphyxia

Bonestroo¹,

Heijnen²,

Groenendaal

et al. 2015

Dev Neurosci

Self Cite

View full text Add to dashboard Cite

Antenatal inflammation is associated with increased severity of hypoxic-ischemic (HI) encephalopathy and adverse outcome in human neonates and experimental rodents. We investigated the effect of lipopolysaccharide (LPS) on the timing of HI-induced cerebral tissue loss and gray matter injury, white matter injury and integrity, and the cerebral inflammatory response. On postnatal day 9, mice underwent HI by unilateral carotid artery occlusion followed by systemic hypoxia which resulted in early neuronal damage (MAP2 loss) at 3 h that did not increase up to day 15. LPS injection 14 h before HI (LPS+HI) significantly and gradually aggravated MAP2 loss from 3 h up to day 15, resulting in an acellular cystic lesion. LPS+HI increased white matter damage, reduced myelination in the corpus callosum and increased white matter fiber coherency in the cingulum. The number of oligodendrocytes throughout the lineage (Olig2-positive) was increased whereas more mature myelinating (CNPase-positive) oligodendrocytes were strongly decreased after LPS+HI. LPS+HI induced an increased and prolonged expression of cerebral cytokines/chemokines compared to HI. Additionally, LPS+HI increased macrophage/microglia activation and influx of neutrophils in the brain compared to HI. This study demonstrates the sensitizing effect of LPS on neonatal HI brain injury for an extended time-frame up to 15 days postinsult. LPS before HI induced a gradual increase in gray and white matter deficits, including reduced numbers of more mature myelinating oligodendrocytes and a decrease in white matter integrity. Moreover, LPS+HI prolonged and intensified the cerebral inflammatory response, including cellular infiltration. In conclusion, as the timing of damage and/or involved pathways are changed when HI is preceded by inflammation, experimental therapies might require modifications in the time window, dosage or combinations of therapies for efficacious neuroprotection.

show abstract

Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Development of Cerebral Gray and White Matter Injury and Cerebral Inflammation over Time after Inflammatory Perinatal Asphyxia

Bonestroo¹,

Heijnen²,

Groenendaal

et al. 2015

Dev Neurosci

Self Cite

View full text Add to dashboard Cite

show abstract

“…Interestingly, stroke induces changes in the miRNA profile of MSCs and within their released exosomes [118]. In line with the broad neuroprotective effect exerted by MSCs, Van Velthoven et al demonstrated that local administration of MSCs could restore functional cortical rewiring and increase axonal connectivity in the ipsilesional hemisphere [119]. Remarkably, also intranasally administered MSCs can decrease brain damage upon neonatal stroke [120].…”

Section: Ischemic Strokementioning

confidence: 99%

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

2015

View full text Add to dashboard Cite

“…IC is the most important type of white matter in the brain. 33 Motor axons form a tract running from the ipsilateral cortex and passing through the ipsilateral IC toward the contralateral spinal cord. FA is directly related to histological markers of myelination.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effects of Transplanted Endothelial Progenitor Cells and RWJ 67657 in Diabetic Ischemic Stroke Models

Bai

Wang

Chen

et al. 2015

Stroke

View full text Add to dashboard Cite

Background and Purpose— An immature vascular phenotype in diabetes mellitus may cause more severe vascular damage and poorer functional outcomes after stroke, and it would be feasible to repair damaged functional vessels using endothelial progenitor cell (EPC) transplantation. However, high glucose induces p38 mitogen-activated protein kinase activation, which can accelerate the senescence and apoptosis of EPCs. The aim of this study was to investigate the combined effects of EPC transplantation and p38 mitogen-activated protein kinase inhibitor administration on diabetic stroke outcomes. Methods— Bone marrow–derived EPCs were injected intra-arterially into db/db mice after ischemic stroke induction. RWJ 67657 (RWJ), a p38 mitogen-activated protein kinase inhibitor, was administered orally for 7 consecutive days, with the first dose given 30 minutes before stroke induction. Functional outcome was determined at days 0, 1, 7, 14, and 21. Angiogenesis, neurogenesis, infarct volume, and Western blotting assays were performed on day 7, and white matter remodeling was determined on day 14. Results— Neither EPC transplantation nor RWJ administration alone significantly improved diabetic stroke outcome although RWJ displayed a potent anti-inflammatory effect. By both improving the functioning of EPCs and reducing inflammation, EPC transplantation plus RWJ administration in vivo synergistically promoted angiogenesis and neurogenesis after diabetic stroke. In addition, the white matter remodeling, behavioral scores, and expressions of vascular endothelial growth factor and brain-derived neurotrophic factor were significantly increased in diabetic mice treated with both EPCs and RWJ. Conclusions— The combination of EPC transplantation and RWJ administration accelerated recovery from diabetic stroke, which might have been caused by increased levels of proangiogenic and neurotrophic factors.

show abstract

Mesenchymal stem cells restore cortical rewiring after neonatal ischemia in mice

Abstract: This is the first study to describe MSC treatment after neonatal HI markedly reducing contralesional axonal remodeling induced by HI brain injury.

Cited by 62 publications

References 44 publications

Development of Cerebral Gray and White Matter Injury and Cerebral Inflammation over Time after Inflammatory Perinatal Asphyxia

Development of Cerebral Gray and White Matter Injury and Cerebral Inflammation over Time after Inflammatory Perinatal Asphyxia

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

Synergistic Effects of Transplanted Endothelial Progenitor Cells and RWJ 67657 in Diabetic Ischemic Stroke Models

Contact Info

Product

Resources

About