Hyaluronidase and Hyaluronan oligosaccharides promote neurological recovery after intraventricular hemorrhage

Govindaiah Vinukonda, Preeti Dohare, Arslan Arshad, Muhammad T. Zia, Sanjeet Panda, Ritesh Korumilli, Robert Kayton, Vincent C. Hascall, Mark E. Lauer, Praveen Ballabh

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 ofHAby 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,weused the preterm rabbit model of glycerol-inducedIVHand analyzed autopsy samples from premature infants.Wefound that totalHAlevels were comparable in both preterm rabbit pups andhumaninfants 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 and tumor necrosis factor-stimulated gene-6 were elevated in newborns with IVH; and depletion of HC–HA levels by HA oligosaccharide treatment reduced inflammation and enhanced myelination and neurological recovery in rabbits with IVH. Hence, hyaluronidase or HA oligosaccharide treatment represses inflammation, promotes OPC maturation, and restores myelination and neurological function in rabbits with IVH. These therapeutic strategies might improve the neurological outcome of premature infants with IVH.

Original languageEnglish (US)
Pages (from-to)872-889
Number of pages18
JournalJournal of Neuroscience
Volume36
Issue number3
DOIs
StatePublished - Jan 20 2016
Externally publishedYes

Fingerprint

Hyaluronoglucosaminidase
Hyaluronic Acid
Oligosaccharides
Hemorrhage
Oligodendroglia
Rabbits
Stem Cells
Premature Infants
Inflammation
CD44 Antigens
Therapeutics
Microglia
Prosencephalon
Glycerol
Survivors
Autopsy
Glycoproteins
Tumor Necrosis Factor-alpha
Newborn Infant
Cytokines

Keywords

  • Hyaluronan
  • Hyaluronan oligosaccharides
  • Hyaluronidase
  • Microglia
  • Myelination
  • Oligodendrocyte

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hyaluronidase and Hyaluronan oligosaccharides promote neurological recovery after intraventricular hemorrhage. / Vinukonda, Govindaiah; Dohare, Preeti; Arshad, Arslan; Zia, Muhammad T.; Panda, Sanjeet; Korumilli, Ritesh; Kayton, Robert; Hascall, Vincent C.; Lauer, Mark E.; Ballabh, Praveen.

In: Journal of Neuroscience, Vol. 36, No. 3, 20.01.2016, p. 872-889.

Research output: Contribution to journalArticle

Vinukonda, G, Dohare, P, Arshad, A, Zia, MT, Panda, S, Korumilli, R, Kayton, R, Hascall, VC, Lauer, ME & Ballabh, P 2016, 'Hyaluronidase and Hyaluronan oligosaccharides promote neurological recovery after intraventricular hemorrhage', Journal of Neuroscience, vol. 36, no. 3, pp. 872-889. https://doi.org/10.1523/JNEUROSCI.3297-15.2016
Vinukonda, Govindaiah ; Dohare, Preeti ; Arshad, Arslan ; Zia, Muhammad T. ; Panda, Sanjeet ; Korumilli, Ritesh ; Kayton, Robert ; Hascall, Vincent C. ; Lauer, Mark E. ; Ballabh, Praveen. / Hyaluronidase and Hyaluronan oligosaccharides promote neurological recovery after intraventricular hemorrhage. In: Journal of Neuroscience. 2016 ; Vol. 36, No. 3. pp. 872-889.
@article{513f0874ffa04b5ca52e224d9be8dcc3,
title = "Hyaluronidase and Hyaluronan oligosaccharides promote neurological recovery after intraventricular hemorrhage",
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 ofHAby 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,weused the preterm rabbit model of glycerol-inducedIVHand analyzed autopsy samples from premature infants.Wefound that totalHAlevels were comparable in both preterm rabbit pups andhumaninfants 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 and tumor necrosis factor-stimulated gene-6 were elevated in newborns with IVH; and depletion of HC–HA levels by HA oligosaccharide treatment reduced inflammation and enhanced myelination and neurological recovery in rabbits with IVH. Hence, hyaluronidase or HA oligosaccharide treatment represses inflammation, promotes OPC maturation, and restores myelination and neurological function in rabbits with IVH. These therapeutic strategies might improve the neurological outcome of premature infants with IVH.",
keywords = "Hyaluronan, Hyaluronan oligosaccharides, Hyaluronidase, Microglia, Myelination, Oligodendrocyte",
author = "Govindaiah Vinukonda and Preeti Dohare and Arslan Arshad and Zia, {Muhammad T.} and Sanjeet Panda and Ritesh Korumilli and Robert Kayton and Hascall, {Vincent C.} and Lauer, {Mark E.} and Praveen Ballabh",
year = "2016",
month = "1",
day = "20",
doi = "10.1523/JNEUROSCI.3297-15.2016",
language = "English (US)",
volume = "36",
pages = "872--889",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "3",

}

TY - JOUR

T1 - Hyaluronidase and Hyaluronan oligosaccharides promote neurological recovery after intraventricular hemorrhage

AU - Vinukonda, Govindaiah

AU - Dohare, Preeti

AU - Arshad, Arslan

AU - Zia, Muhammad T.

AU - Panda, Sanjeet

AU - Korumilli, Ritesh

AU - Kayton, Robert

AU - Hascall, Vincent C.

AU - Lauer, Mark E.

AU - Ballabh, Praveen

PY - 2016/1/20

Y1 - 2016/1/20

N2 - 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 ofHAby 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,weused the preterm rabbit model of glycerol-inducedIVHand analyzed autopsy samples from premature infants.Wefound that totalHAlevels were comparable in both preterm rabbit pups andhumaninfants 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 and tumor necrosis factor-stimulated gene-6 were elevated in newborns with IVH; and depletion of HC–HA levels by HA oligosaccharide treatment reduced inflammation and enhanced myelination and neurological recovery in rabbits with IVH. Hence, hyaluronidase or HA oligosaccharide treatment represses inflammation, promotes OPC maturation, and restores myelination and neurological function in rabbits with IVH. These therapeutic strategies might improve the neurological outcome of premature infants with IVH.

AB - 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 ofHAby 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,weused the preterm rabbit model of glycerol-inducedIVHand analyzed autopsy samples from premature infants.Wefound that totalHAlevels were comparable in both preterm rabbit pups andhumaninfants 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 and tumor necrosis factor-stimulated gene-6 were elevated in newborns with IVH; and depletion of HC–HA levels by HA oligosaccharide treatment reduced inflammation and enhanced myelination and neurological recovery in rabbits with IVH. Hence, hyaluronidase or HA oligosaccharide treatment represses inflammation, promotes OPC maturation, and restores myelination and neurological function in rabbits with IVH. These therapeutic strategies might improve the neurological outcome of premature infants with IVH.

KW - Hyaluronan

KW - Hyaluronan oligosaccharides

KW - Hyaluronidase

KW - Microglia

KW - Myelination

KW - Oligodendrocyte

UR - http://www.scopus.com/inward/record.url?scp=84955125461&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955125461&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.3297-15.2016

DO - 10.1523/JNEUROSCI.3297-15.2016

M3 - Article

VL - 36

SP - 872

EP - 889

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 3

ER -