Human umbilical cord therapy improves long-term behavioral outcomes following neonatal hypoxic ischemic brain injury

Tayla R. Penny, Amy E. Sutherland, Jamie G. Mihelakis, Madison C.B. Paton, Yen Pham, Joohyung Lee, Nicole M. Jones, Graham Jenkin, Michael C. Fahey, Suzanne L. Miller, Courtney A. McDonald

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Background: Hypoxic ischemic (HI) insult in term babies at labor or birth can cause long-term neurodevelopmental disorders, including cerebral palsy (CP). The current standard treatment for term infants with hypoxic ischemic encephalopathy (HIE) is hypothermia. Because hypothermia is only partially effective, novel therapies are required to improve outcomes further. Human umbilical cord blood cells (UCB) are a rich source of stem and progenitor cells making them a potential treatment for neonatal HI brain injury. Recent clinical trials have shown that UCB therapy is a safe and efficacious treatment for confirmed cerebral palsy. In this study, we assessed whether early administration of UCB to the neonate could improve long-term behavioral outcomes and promote brain repair following neonatal HI brain injury. Methods: HI brain injury was induced in postnatal day (PND) 7 rat pups via permanent ligation of the left carotid artery, followed by a 90 min hypoxic challenge. UCB was administered intraperitoneally on PND 8. Behavioral tests, including negative geotaxis, forelimb preference and open field test, were performed on PND 14, 30, and 50, following brains were collected for assessment of neuropathology. Results: Neonatal HI resulted in decreased brain weight, cerebral tissue loss and apoptosis in the somatosensory cortex, as well as compromised behavioral outcomes. UCB administration following HI improved short and long-term behavioral outcomes but did not reduce long-term histological evidence of brain injury compared to HI alone. In addition, UCB following HI increased microglia activation in the somatosensory cortex compared to HI alone. Conclusion: Administration of a single dose of UCB cells 24 h after HI injury improves behavior, however, a single dose of cells does not modulate pathological evidence of long-term brain injury.

Original languageEnglish
Article number283
Number of pages11
JournalFrontiers in Physiology
Volume10
Issue numberMAR
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Behavior
  • Cerebral palsy
  • Hypoxia ischemia
  • Hypoxic ischemic encephalopathy
  • Stem cells
  • Umbilical cord blood

Cite this

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title = "Human umbilical cord therapy improves long-term behavioral outcomes following neonatal hypoxic ischemic brain injury",
abstract = "Background: Hypoxic ischemic (HI) insult in term babies at labor or birth can cause long-term neurodevelopmental disorders, including cerebral palsy (CP). The current standard treatment for term infants with hypoxic ischemic encephalopathy (HIE) is hypothermia. Because hypothermia is only partially effective, novel therapies are required to improve outcomes further. Human umbilical cord blood cells (UCB) are a rich source of stem and progenitor cells making them a potential treatment for neonatal HI brain injury. Recent clinical trials have shown that UCB therapy is a safe and efficacious treatment for confirmed cerebral palsy. In this study, we assessed whether early administration of UCB to the neonate could improve long-term behavioral outcomes and promote brain repair following neonatal HI brain injury. Methods: HI brain injury was induced in postnatal day (PND) 7 rat pups via permanent ligation of the left carotid artery, followed by a 90 min hypoxic challenge. UCB was administered intraperitoneally on PND 8. Behavioral tests, including negative geotaxis, forelimb preference and open field test, were performed on PND 14, 30, and 50, following brains were collected for assessment of neuropathology. Results: Neonatal HI resulted in decreased brain weight, cerebral tissue loss and apoptosis in the somatosensory cortex, as well as compromised behavioral outcomes. UCB administration following HI improved short and long-term behavioral outcomes but did not reduce long-term histological evidence of brain injury compared to HI alone. In addition, UCB following HI increased microglia activation in the somatosensory cortex compared to HI alone. Conclusion: Administration of a single dose of UCB cells 24 h after HI injury improves behavior, however, a single dose of cells does not modulate pathological evidence of long-term brain injury.",
keywords = "Behavior, Cerebral palsy, Hypoxia ischemia, Hypoxic ischemic encephalopathy, Stem cells, Umbilical cord blood",
author = "Penny, {Tayla R.} and Sutherland, {Amy E.} and Mihelakis, {Jamie G.} and Paton, {Madison C.B.} and Yen Pham and Joohyung Lee and Jones, {Nicole M.} and Graham Jenkin and Fahey, {Michael C.} and Miller, {Suzanne L.} and McDonald, {Courtney A.}",
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Human umbilical cord therapy improves long-term behavioral outcomes following neonatal hypoxic ischemic brain injury. / Penny, Tayla R.; Sutherland, Amy E.; Mihelakis, Jamie G.; Paton, Madison C.B.; Pham, Yen; Lee, Joohyung; Jones, Nicole M.; Jenkin, Graham; Fahey, Michael C.; Miller, Suzanne L.; McDonald, Courtney A.

In: Frontiers in Physiology, Vol. 10, No. MAR, 283, 01.01.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Human umbilical cord therapy improves long-term behavioral outcomes following neonatal hypoxic ischemic brain injury

AU - Penny, Tayla R.

AU - Sutherland, Amy E.

AU - Mihelakis, Jamie G.

AU - Paton, Madison C.B.

AU - Pham, Yen

AU - Lee, Joohyung

AU - Jones, Nicole M.

AU - Jenkin, Graham

AU - Fahey, Michael C.

AU - Miller, Suzanne L.

AU - McDonald, Courtney A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Hypoxic ischemic (HI) insult in term babies at labor or birth can cause long-term neurodevelopmental disorders, including cerebral palsy (CP). The current standard treatment for term infants with hypoxic ischemic encephalopathy (HIE) is hypothermia. Because hypothermia is only partially effective, novel therapies are required to improve outcomes further. Human umbilical cord blood cells (UCB) are a rich source of stem and progenitor cells making them a potential treatment for neonatal HI brain injury. Recent clinical trials have shown that UCB therapy is a safe and efficacious treatment for confirmed cerebral palsy. In this study, we assessed whether early administration of UCB to the neonate could improve long-term behavioral outcomes and promote brain repair following neonatal HI brain injury. Methods: HI brain injury was induced in postnatal day (PND) 7 rat pups via permanent ligation of the left carotid artery, followed by a 90 min hypoxic challenge. UCB was administered intraperitoneally on PND 8. Behavioral tests, including negative geotaxis, forelimb preference and open field test, were performed on PND 14, 30, and 50, following brains were collected for assessment of neuropathology. Results: Neonatal HI resulted in decreased brain weight, cerebral tissue loss and apoptosis in the somatosensory cortex, as well as compromised behavioral outcomes. UCB administration following HI improved short and long-term behavioral outcomes but did not reduce long-term histological evidence of brain injury compared to HI alone. In addition, UCB following HI increased microglia activation in the somatosensory cortex compared to HI alone. Conclusion: Administration of a single dose of UCB cells 24 h after HI injury improves behavior, however, a single dose of cells does not modulate pathological evidence of long-term brain injury.

AB - Background: Hypoxic ischemic (HI) insult in term babies at labor or birth can cause long-term neurodevelopmental disorders, including cerebral palsy (CP). The current standard treatment for term infants with hypoxic ischemic encephalopathy (HIE) is hypothermia. Because hypothermia is only partially effective, novel therapies are required to improve outcomes further. Human umbilical cord blood cells (UCB) are a rich source of stem and progenitor cells making them a potential treatment for neonatal HI brain injury. Recent clinical trials have shown that UCB therapy is a safe and efficacious treatment for confirmed cerebral palsy. In this study, we assessed whether early administration of UCB to the neonate could improve long-term behavioral outcomes and promote brain repair following neonatal HI brain injury. Methods: HI brain injury was induced in postnatal day (PND) 7 rat pups via permanent ligation of the left carotid artery, followed by a 90 min hypoxic challenge. UCB was administered intraperitoneally on PND 8. Behavioral tests, including negative geotaxis, forelimb preference and open field test, were performed on PND 14, 30, and 50, following brains were collected for assessment of neuropathology. Results: Neonatal HI resulted in decreased brain weight, cerebral tissue loss and apoptosis in the somatosensory cortex, as well as compromised behavioral outcomes. UCB administration following HI improved short and long-term behavioral outcomes but did not reduce long-term histological evidence of brain injury compared to HI alone. In addition, UCB following HI increased microglia activation in the somatosensory cortex compared to HI alone. Conclusion: Administration of a single dose of UCB cells 24 h after HI injury improves behavior, however, a single dose of cells does not modulate pathological evidence of long-term brain injury.

KW - Behavior

KW - Cerebral palsy

KW - Hypoxia ischemia

KW - Hypoxic ischemic encephalopathy

KW - Stem cells

KW - Umbilical cord blood

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U2 - 10.3389/fphys.2019.00283

DO - 10.3389/fphys.2019.00283

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VL - 10

JO - Frontiers in Physiology

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SN - 1664-042X

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