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Endogenous Stem Cell-Based Brain Remodeling in Mammals pp 159–175Cite as

Oligodendrocyte Progenitors and Brain Remodeling Following Blood–Brain Barrier Rupture

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Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

Blood–brain barrier rupture is typically seen in germinal matrix hemorrhage–intraventricular hemorrhage (GMH–IVH) of premature infants. The development of IVH results in remodeling of the periventricular germinal matrix and the white matter. The onset of hemorrhage initiates a cascade of events, including inflammation, microglial activation, astrocytosis, and degeneration along with arrested maturation of oligodendrocytes. These processes contribute to myelination failure, and the survivors of IVH manifest with cerebral palsy, cognitive deficits, and mental retardation. The main focus of this chapter is to discuss how the rupture of the blood–brain barrier and subsequent hemorrhage disrupts survival and maturation of oligodendrocytes. I also critically evaluate the recently employed strategies to restore maturation of oligodendrocytes and myelination in animal models of hemorrhage. Translation of these preclinical studies into controlled clinical trials may lead to discoveries in the treatment of posthemorrhagic white matter injury in premature infants.

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Abbreviations

BBB:

Blood–brain barrier

BMP:

Bone morphogenetic protein

ChABC:

Chondroitinase ABC

CNPase:

2′,3′-Cyclic nucleotide 3′-phosphodiesterase

COX-2:

Cyclooxygenase-2

CSPG:

Chondroitin sulfate proteoglycan

GFAP:

Glial fibrillary acidic protein

GMH:

Germinal matrix hemorrhage

IL1:

Interleukin-1

IVH:

Intraventricular hemorrhage

MAG:

Myelin-associated glycoprotein

MBP:

Myelin basic protein

Ngn:

Neurogenin

PDGFRα:

Platelet-derived growth factor α

PLP:

Proteolipid protein

PVL:

Periventricular leukomalacia

Shh:

Sonic hedgehog

SVZ:

Subventricular zone

TJ:

Tight junction

TNF-α:

Tumor necrosis factor-α

VEGF:

Vascular endothelial growth factor

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Acknowledgements

Authors thank Joanne Abrahams for the assistance with images.

Source of funding: NIH/NINDS grant RO1 NS071263 (PB).

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Authors and Affiliations

  1. Department of Pediatrics, Cell Biology, and Anatomy, Regional Neonatal Center, Maria Fareri Children’s Hospital at Westchester Medical Center-New York Medical College, Valhalla, NY, USA

    Praveen Ballabh M.D.

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  1. Praveen Ballabh M.D.
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Correspondence to Praveen Ballabh M.D. .

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Editors and Affiliations

  1. French Institute of Health and Medical Research U1130, French National Center for Scientific Research, Pierre-and-Marie-Curie University, Paris, France

    Marie-Pierre Junier

  2. Departments of Pediatrics and Pathology & Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York, USA

    Steven G. Kernie

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Ballabh, P. (2014). Oligodendrocyte Progenitors and Brain Remodeling Following Blood–Brain Barrier Rupture. In: Junier, MP., Kernie, S. (eds) Endogenous Stem Cell-Based Brain Remodeling in Mammals. Stem Cell Biology and Regenerative Medicine. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7399-3_8

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