White matter injury in infants with intraventricular haemorrhage: mechanisms and therapies
Ballabh, Praveen; de Vries, Linda S
(2021) Nature Reviews Neurology, volume 17, issue 4, pp. 199 - 214
(Article)
Abstract
Intraventricular haemorrhage (IVH) continues to be a major complication of prematurity that can result in cerebral palsy and cognitive impairment in survivors. No optimal therapy exists to prevent IVH or to treat its consequences. IVH varies in severity and can present as a bleed confined to the germinal matrix, small-to-large
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IVH or periventricular haemorrhagic infarction. Moderate-to-severe haemorrhage dilates the ventricle and damages the periventricular white matter. This white matter injury results from a constellation of blood-induced pathological reactions, including oxidative stress, glutamate excitotoxicity, inflammation, perturbed signalling pathways and remodelling of the extracellular matrix. Potential therapies for IVH are currently undergoing investigation in preclinical models and evidence from clinical trials suggests that stem cell treatment and/or endoscopic removal of clots from the cerebral ventricles could transform the outcome of infants with IVH. This Review presents an integrated view of new insights into the mechanisms underlying white matter injury in premature infants with IVH and highlights the importance of early detection of disability and immediate intervention in optimizing the outcomes of IVH survivors.
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Keywords: Clinical Neurology, Cellular and Molecular Neuroscience, Review, Journal Article
ISSN: 1759-4758
Publisher: Nature Publishing Group
Note: Funding Information: The authors sincerely thank Robert Hevner, University of California San Diego, CA, USA, for the images of brain slices from a human premature infant with IVH in Figs 1a and 1b. The authors also sincerely thank George Kleinman, New York Medical College, Valhalla, NY, USA, and Peter Nikkels, University Medical Center, Utrecht, the Netherlands, for the images of brain slices from a human premature infant with IVH in Figs 1c and 1d, respectively. The authors are grateful to Joseph Volpe, Harvard University, Boston, MA, USA, for a critical review of the manuscript. The authors’ research work is supported by NIH grants RO1 NS110760 and R21NS102897 (both to P.B.). Publisher Copyright: © 2021, Springer Nature Limited.
(Peer reviewed)