Antenatal allopurinol reduces hippocampal brain damageafter acute birth asphyxia in late gestation fetal sheep.

J.J. Kaandorp; J.B. Derks; M.A. Oudijk; H.L. Torrance; M.G. Harmsen; P.G.J. Nikkels; F. van Bel; G.H.A. Visser; D.A. Giussani

doi:10.1177/1933719113493516

Antenatal allopurinol reduces hippocampal brain damageafter acute birth asphyxia in late gestation fetal sheep.

Translated title of the contribution: Antenatal allopurinol reduces hippocampal brain damageafter acute birth asphyxia in late gestation fetal sheep.

J.J. Kaandorp
, J.B. Derks
, M.A. Oudijk
, H.L. Torrance
, M.G. Harmsen
, P.G.J. Nikkels
, F. van Bel
, G.H.A. Visser
, D.A. Giussani

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Free radical-induced reperfusion injury is a recognized cause of brain damage in the newborn after birth asphyxia. The xanthine oxidase inhibitor allopurinol reduces free radical synthesis and crosses the placenta easily. Therefore, allopurinol is a promising therapeutic candidate. This study tested the hypothesis that maternal treatment with allopurinol during fetal asphyxia limits ischemia-reperfusion (I/R) damage to the fetal brain in ovine pregnancy. The I/R challenge was induced by 5 repeated measured compressions of the umbilical cord, each lasting 10 minutes, in chronically instrumented fetal sheep at 0.8 of gestation. Relative to control fetal brains, the I/R challenge induced significant neuronal damage in the fetal hippocampal cornu ammonis zones 3 and 4. Maternal treatment with allopurinol during the I/R challenge restored the fetal neuronal damage toward control scores. Maternal treatment with allopurinol offers potential neuroprotection to the fetal brain in the clinical management of perinatal asphyxia.

Translated title of the contribution	Antenatal allopurinol reduces hippocampal brain damageafter acute birth asphyxia in late gestation fetal sheep.
Original language	Undefined/Unknown
Pages (from-to)	251-259
Number of pages	9
Journal	Reproductive Sciences
Volume	21
Issue number	2
DOIs	https://doi.org/10.1177/1933719113493516
Publication status	Published - Feb 2014

Keywords

sheep
fetus
asphyxia
allopurinol
neuroprotection
UMBILICAL-CORD OCCLUSION
HYPOXIC-ISCHEMIC ENCEPHALOPATHY
PERINATAL ASPHYXIA
XANTHINE-OXIDASE
NEAR-TERM
NEONATAL ENCEPHALOPATHY
OXIDATIVE STRESS
BLOOD-LEVELS
INJURY
PRETERM

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10.1177/1933719113493516

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title = "Antenatal allopurinol reduces hippocampal brain damageafter acute birth asphyxia in late gestation fetal sheep.",

abstract = "Free radical-induced reperfusion injury is a recognized cause of brain damage in the newborn after birth asphyxia. The xanthine oxidase inhibitor allopurinol reduces free radical synthesis and crosses the placenta easily. Therefore, allopurinol is a promising therapeutic candidate. This study tested the hypothesis that maternal treatment with allopurinol during fetal asphyxia limits ischemia-reperfusion (I/R) damage to the fetal brain in ovine pregnancy. The I/R challenge was induced by 5 repeated measured compressions of the umbilical cord, each lasting 10 minutes, in chronically instrumented fetal sheep at 0.8 of gestation. Relative to control fetal brains, the I/R challenge induced significant neuronal damage in the fetal hippocampal cornu ammonis zones 3 and 4. Maternal treatment with allopurinol during the I/R challenge restored the fetal neuronal damage toward control scores. Maternal treatment with allopurinol offers potential neuroprotection to the fetal brain in the clinical management of perinatal asphyxia.",

keywords = "sheep, fetus, asphyxia, allopurinol, neuroprotection, UMBILICAL-CORD OCCLUSION, HYPOXIC-ISCHEMIC ENCEPHALOPATHY, PERINATAL ASPHYXIA, XANTHINE-OXIDASE, NEAR-TERM, NEONATAL ENCEPHALOPATHY, OXIDATIVE STRESS, BLOOD-LEVELS, INJURY, PRETERM",

author = "J.J. Kaandorp and J.B. Derks and M.A. Oudijk and H.L. Torrance and M.G. Harmsen and P.G.J. Nikkels and \{van Bel\}, F. and G.H.A. Visser and D.A. Giussani",

year = "2014",

month = feb,

doi = "10.1177/1933719113493516",

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volume = "21",

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journal = "Reproductive Sciences",

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T1 - Antenatal allopurinol reduces hippocampal brain damageafter acute birth asphyxia in late gestation fetal sheep.

AU - Kaandorp, J.J.

AU - Derks, J.B.

AU - Oudijk, M.A.

AU - Torrance, H.L.

AU - Harmsen, M.G.

AU - Nikkels, P.G.J.

AU - van Bel, F.

AU - Visser, G.H.A.

AU - Giussani, D.A.

PY - 2014/2

Y1 - 2014/2

N2 - Free radical-induced reperfusion injury is a recognized cause of brain damage in the newborn after birth asphyxia. The xanthine oxidase inhibitor allopurinol reduces free radical synthesis and crosses the placenta easily. Therefore, allopurinol is a promising therapeutic candidate. This study tested the hypothesis that maternal treatment with allopurinol during fetal asphyxia limits ischemia-reperfusion (I/R) damage to the fetal brain in ovine pregnancy. The I/R challenge was induced by 5 repeated measured compressions of the umbilical cord, each lasting 10 minutes, in chronically instrumented fetal sheep at 0.8 of gestation. Relative to control fetal brains, the I/R challenge induced significant neuronal damage in the fetal hippocampal cornu ammonis zones 3 and 4. Maternal treatment with allopurinol during the I/R challenge restored the fetal neuronal damage toward control scores. Maternal treatment with allopurinol offers potential neuroprotection to the fetal brain in the clinical management of perinatal asphyxia.

AB - Free radical-induced reperfusion injury is a recognized cause of brain damage in the newborn after birth asphyxia. The xanthine oxidase inhibitor allopurinol reduces free radical synthesis and crosses the placenta easily. Therefore, allopurinol is a promising therapeutic candidate. This study tested the hypothesis that maternal treatment with allopurinol during fetal asphyxia limits ischemia-reperfusion (I/R) damage to the fetal brain in ovine pregnancy. The I/R challenge was induced by 5 repeated measured compressions of the umbilical cord, each lasting 10 minutes, in chronically instrumented fetal sheep at 0.8 of gestation. Relative to control fetal brains, the I/R challenge induced significant neuronal damage in the fetal hippocampal cornu ammonis zones 3 and 4. Maternal treatment with allopurinol during the I/R challenge restored the fetal neuronal damage toward control scores. Maternal treatment with allopurinol offers potential neuroprotection to the fetal brain in the clinical management of perinatal asphyxia.

KW - sheep

KW - fetus

KW - asphyxia

KW - allopurinol

KW - neuroprotection

KW - UMBILICAL-CORD OCCLUSION

KW - HYPOXIC-ISCHEMIC ENCEPHALOPATHY

KW - PERINATAL ASPHYXIA

KW - XANTHINE-OXIDASE

KW - NEAR-TERM

KW - NEONATAL ENCEPHALOPATHY

KW - OXIDATIVE STRESS

KW - BLOOD-LEVELS

KW - INJURY

KW - PRETERM

U2 - 10.1177/1933719113493516

DO - 10.1177/1933719113493516

M3 - Article

C2 - 23793473

SN - 1933-7191

VL - 21

SP - 251

EP - 259

JO - Reproductive Sciences

JF - Reproductive Sciences

IS - 2

ER -

Antenatal allopurinol reduces hippocampal brain damageafter acute birth asphyxia in late gestation fetal sheep.

Abstract

Keywords

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