Preterm white matter brain injury is prevented by early administration of umbilical cord blood cells

Jingang Li, Tamara Yawno, Amy Sutherland, Jan Loose, Ilias Nitsos, Robert Bischof, Margie Castillo-Melendez, Courtney A McDonald, Flora Y. Wong, Graham Jenkin, Suzanne Lee Miller

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Abstract

Infants born very preterm are at high risk for neurological deficits including cerebral palsy. In this study we assessed the neuroprotective effects of umbilical cord blood cells (UCBCs) and optimal administration timing in a fetal sheep model of preterm brain injury. 50 million allogeneic UCBCs were intravenously administered to fetal sheep (0.7 gestation) at 12 h or 5 d after acute hypoxia-ischemia (HI) induced by umbilical cord occlusion. The fetal brains were collected at 10 d after HI. HI (n = 7) was associated with reduced number of oligodendrocytes (Olig2+) and myelin density (CNPase+), and increased density of activated microglia (Iba-1+) in cerebral white matter compared to control fetuses (P < 0.05). UCBCs administered at 12 h, but not 5 d after HI, significantly protected white matter structures and suppressed cerebral inflammation. Activated microglial density showed a correlation with decreasing oligodendrocyte number (P < 0.001). HI caused cell death (TUNEL+) in the internal capsule and cell proliferation (Ki-67 +) in the subventricular zone compared to control (P < 0.05), while UCBCs at 12 h or 5 d ameliorated these effects. Additionally, UCBCs at 12 h induced a significant systemic increase in interleukin-10 at 10 d, and reduced oxidative stress (malondialdehyde) following HI (P < 0.05). UCBC administration at 12 h after HI reduces preterm white matter injury, via anti-inflammatory and antioxidant actions.
Original languageEnglish
Pages (from-to)179-187
Number of pages9
JournalExperimental Neurology
Volume283
Issue numberPart A
DOIs
Publication statusPublished - Sep 2016

Keywords

  • Hypoxia-ischemia
  • Neuroprotection
  • Oligodendrocytes
  • Preterm infants
  • Stem cell
  • Umbilical cord blood therapy
  • White matter brain injury

Cite this

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title = "Preterm white matter brain injury is prevented by early administration of umbilical cord blood cells",
abstract = "Infants born very preterm are at high risk for neurological deficits including cerebral palsy. In this study we assessed the neuroprotective effects of umbilical cord blood cells (UCBCs) and optimal administration timing in a fetal sheep model of preterm brain injury. 50 million allogeneic UCBCs were intravenously administered to fetal sheep (0.7 gestation) at 12 h or 5 d after acute hypoxia-ischemia (HI) induced by umbilical cord occlusion. The fetal brains were collected at 10 d after HI. HI (n = 7) was associated with reduced number of oligodendrocytes (Olig2+) and myelin density (CNPase+), and increased density of activated microglia (Iba-1+) in cerebral white matter compared to control fetuses (P < 0.05). UCBCs administered at 12 h, but not 5 d after HI, significantly protected white matter structures and suppressed cerebral inflammation. Activated microglial density showed a correlation with decreasing oligodendrocyte number (P < 0.001). HI caused cell death (TUNEL+) in the internal capsule and cell proliferation (Ki-67 +) in the subventricular zone compared to control (P < 0.05), while UCBCs at 12 h or 5 d ameliorated these effects. Additionally, UCBCs at 12 h induced a significant systemic increase in interleukin-10 at 10 d, and reduced oxidative stress (malondialdehyde) following HI (P < 0.05). UCBC administration at 12 h after HI reduces preterm white matter injury, via anti-inflammatory and antioxidant actions.",
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author = "Jingang Li and Tamara Yawno and Amy Sutherland and Jan Loose and Ilias Nitsos and Robert Bischof and Margie Castillo-Melendez and McDonald, {Courtney A} and Wong, {Flora Y.} and Graham Jenkin and Miller, {Suzanne Lee}",
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Preterm white matter brain injury is prevented by early administration of umbilical cord blood cells. / Li, Jingang; Yawno, Tamara; Sutherland, Amy; Loose, Jan ; Nitsos, Ilias; Bischof, Robert ; Castillo-Melendez, Margie; McDonald, Courtney A; Wong, Flora Y.; Jenkin, Graham; Miller, Suzanne Lee.

In: Experimental Neurology, Vol. 283, No. Part A, 09.2016, p. 179-187.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Preterm white matter brain injury is prevented by early administration of umbilical cord blood cells

AU - Li, Jingang

AU - Yawno, Tamara

AU - Sutherland, Amy

AU - Loose, Jan

AU - Nitsos, Ilias

AU - Bischof, Robert

AU - Castillo-Melendez, Margie

AU - McDonald, Courtney A

AU - Wong, Flora Y.

AU - Jenkin, Graham

AU - Miller, Suzanne Lee

PY - 2016/9

Y1 - 2016/9

N2 - Infants born very preterm are at high risk for neurological deficits including cerebral palsy. In this study we assessed the neuroprotective effects of umbilical cord blood cells (UCBCs) and optimal administration timing in a fetal sheep model of preterm brain injury. 50 million allogeneic UCBCs were intravenously administered to fetal sheep (0.7 gestation) at 12 h or 5 d after acute hypoxia-ischemia (HI) induced by umbilical cord occlusion. The fetal brains were collected at 10 d after HI. HI (n = 7) was associated with reduced number of oligodendrocytes (Olig2+) and myelin density (CNPase+), and increased density of activated microglia (Iba-1+) in cerebral white matter compared to control fetuses (P < 0.05). UCBCs administered at 12 h, but not 5 d after HI, significantly protected white matter structures and suppressed cerebral inflammation. Activated microglial density showed a correlation with decreasing oligodendrocyte number (P < 0.001). HI caused cell death (TUNEL+) in the internal capsule and cell proliferation (Ki-67 +) in the subventricular zone compared to control (P < 0.05), while UCBCs at 12 h or 5 d ameliorated these effects. Additionally, UCBCs at 12 h induced a significant systemic increase in interleukin-10 at 10 d, and reduced oxidative stress (malondialdehyde) following HI (P < 0.05). UCBC administration at 12 h after HI reduces preterm white matter injury, via anti-inflammatory and antioxidant actions.

AB - Infants born very preterm are at high risk for neurological deficits including cerebral palsy. In this study we assessed the neuroprotective effects of umbilical cord blood cells (UCBCs) and optimal administration timing in a fetal sheep model of preterm brain injury. 50 million allogeneic UCBCs were intravenously administered to fetal sheep (0.7 gestation) at 12 h or 5 d after acute hypoxia-ischemia (HI) induced by umbilical cord occlusion. The fetal brains were collected at 10 d after HI. HI (n = 7) was associated with reduced number of oligodendrocytes (Olig2+) and myelin density (CNPase+), and increased density of activated microglia (Iba-1+) in cerebral white matter compared to control fetuses (P < 0.05). UCBCs administered at 12 h, but not 5 d after HI, significantly protected white matter structures and suppressed cerebral inflammation. Activated microglial density showed a correlation with decreasing oligodendrocyte number (P < 0.001). HI caused cell death (TUNEL+) in the internal capsule and cell proliferation (Ki-67 +) in the subventricular zone compared to control (P < 0.05), while UCBCs at 12 h or 5 d ameliorated these effects. Additionally, UCBCs at 12 h induced a significant systemic increase in interleukin-10 at 10 d, and reduced oxidative stress (malondialdehyde) following HI (P < 0.05). UCBC administration at 12 h after HI reduces preterm white matter injury, via anti-inflammatory and antioxidant actions.

KW - Hypoxia-ischemia

KW - Neuroprotection

KW - Oligodendrocytes

KW - Preterm infants

KW - Stem cell

KW - Umbilical cord blood therapy

KW - White matter brain injury

U2 - 10.1016/j.expneurol.2016.06.017

DO - 10.1016/j.expneurol.2016.06.017

M3 - Article

VL - 283

SP - 179

EP - 187

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - Part A

ER -