Hyaluronidase and Hyaluronan Oligosaccharides Promote Neurological Recovery after Intraventricular Hemorrhage

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Govindaiah VinukondaPraveen Ballabh

Abstract

Intraventricular hemorrhage (IVH) in premature infants results in inflammation, arrested oligodendrocyte progenitor cell (OPC) maturation, and reduced myelination of the white matter. Hyaluronan (HA) inhibits OPC maturation and complexes with the heavy chain (HC) of glycoprotein inter-α-inhibitor to form pathological HA (HC-HA complex), which exacerbates inflammation. Therefore, we hypothesized that IVH would result in accumulation of HA, and that either degradation of HA by hyaluronidase treatment or elimination of HCs from pathological HA by HA oligosaccharide administration would restore OPC maturation, myelination, and neurological function in survivors with IVH. To test these hypotheses, we used the preterm rabbit model of glycerol-induced IVH and analyzed autopsy samples from premature infants. We found that total HA levels were comparable in both preterm rabbit pups and human infants with and without IVH, but HA receptors--CD44, TLR2, TLR4--were elevated in the forebrain of both humans and rabbits with IVH. Hyaluronidase treatment of rabbits with IVH reduced CD44 and TLR4 expression, proinflammatory cytokine levels, and microglia infiltration. It also promoted OPC maturation, myelination, and neurological recovery. HC-HA...Continue Reading

Citations

Oct 27, 2017·Expert Opinion on Therapeutic Targets·Thomas GartonRichard F Keep
Feb 13, 2020·Journal of Clinical Medicine·Davide MarangonMarta Fumagalli
May 23, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Timothy N AudamSteven P Jones
Sep 23, 2020·American Journal of Perinatology·Tania Siahanidou, Christina Spiliopoulou
Sep 15, 2020·Journal of Neonatal-perinatal Medicine·J J Volpe
Jun 13, 2019·Journal of Neurochemistry·Mariko Kato HayashiKaoru Sato
Aug 23, 2020·International Journal of Molecular Sciences·Alec Peters, Larry S Sherman
Nov 12, 2020·International Journal of Molecular Sciences·Isabel Atienza-NavarroMonica Garcia-Alloza
Jan 29, 2021·Nature Reviews. Neurology·Praveen Ballabh, Linda S de Vries
Apr 24, 2021·Seminars in Fetal & Neonatal Medicine·Bokun Cheng, Praveen Ballabh
Sep 23, 2020·Journal of the Mechanical Behavior of Biomedical Materials·Hannah J BaumannNic D Leipzig
Oct 12, 2021·Ageing Research Reviews·Frances Tolibzoda ZakusiloVera Gorbunova

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