Dobutamine treatment reduces inflammation in the preterm fetal sheep brain exposed to acute hypoxia

Nadine Brew, Shinji Nakamura, Nadia Hale, Aminath Azhan, Grace I. Davies, Ilias Nitsos, Suzanne L. Miller, David W. Walker, Flora Y. Wong

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Impaired cerebral autoregulation in preterm infants makes circulatory management important to avoid cerebral hypoxic–ischemic injury. Dobutamine is frequently used as inotropic treatment in preterm neonates, but its effects on the brain exposed to cerebral hypoxia are unknown. We hypothesized that dobutamine would protect the immature brain from cerebral hypoxic injury. Methods: In preterm (0.6 gestation) fetal sheep, dobutamine (Dob, 10 μg/kg/min) or saline (Sal) was infused intravenously for 74 h. Two hours after the beginning of the infusion, umbilical cord occlusion (UCO) was performed to produce fetal asphyxia (Sal+UCO: n = 9, Dob+UCO: n = 7), or sham occlusion (Sal+sham: n = 7, Dob+sham: n = 6) was performed. Brains were collected 72 h later for neuropathology. Results: Dobutamine did not induce cerebral changes in the sham UCO group. UCO increased apoptosis and microglia density in white matter, hippocampus, and caudate nucleus, and astrocyte density in the caudate nucleus. Dobutamine commenced before UCO reduced microglia infiltration in the white matter, and microglial and astrocyte density in the caudate. Conclusion: In preterm hypoxia-induced brain injury, dobutamine decreases neuroinflammation in the white matter and caudate, and reduces astrogliosis in the caudate. Early administration of dobutamine in preterm infants for cardiovascular stabilization appears safe and may be neuroprotective against unforeseeable cerebral hypoxic injury.

Original languageEnglish
Pages (from-to)442-450
Number of pages9
JournalPediatric Research
Volume84
Issue number3
DOIs
Publication statusPublished - 1 Sep 2018

Cite this

Brew, Nadine ; Nakamura, Shinji ; Hale, Nadia ; Azhan, Aminath ; Davies, Grace I. ; Nitsos, Ilias ; Miller, Suzanne L. ; Walker, David W. ; Wong, Flora Y. / Dobutamine treatment reduces inflammation in the preterm fetal sheep brain exposed to acute hypoxia. In: Pediatric Research. 2018 ; Vol. 84, No. 3. pp. 442-450.
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abstract = "Background: Impaired cerebral autoregulation in preterm infants makes circulatory management important to avoid cerebral hypoxic–ischemic injury. Dobutamine is frequently used as inotropic treatment in preterm neonates, but its effects on the brain exposed to cerebral hypoxia are unknown. We hypothesized that dobutamine would protect the immature brain from cerebral hypoxic injury. Methods: In preterm (0.6 gestation) fetal sheep, dobutamine (Dob, 10 μg/kg/min) or saline (Sal) was infused intravenously for 74 h. Two hours after the beginning of the infusion, umbilical cord occlusion (UCO) was performed to produce fetal asphyxia (Sal+UCO: n = 9, Dob+UCO: n = 7), or sham occlusion (Sal+sham: n = 7, Dob+sham: n = 6) was performed. Brains were collected 72 h later for neuropathology. Results: Dobutamine did not induce cerebral changes in the sham UCO group. UCO increased apoptosis and microglia density in white matter, hippocampus, and caudate nucleus, and astrocyte density in the caudate nucleus. Dobutamine commenced before UCO reduced microglia infiltration in the white matter, and microglial and astrocyte density in the caudate. Conclusion: In preterm hypoxia-induced brain injury, dobutamine decreases neuroinflammation in the white matter and caudate, and reduces astrogliosis in the caudate. Early administration of dobutamine in preterm infants for cardiovascular stabilization appears safe and may be neuroprotective against unforeseeable cerebral hypoxic injury.",
author = "Nadine Brew and Shinji Nakamura and Nadia Hale and Aminath Azhan and Davies, {Grace I.} and Ilias Nitsos and Miller, {Suzanne L.} and Walker, {David W.} and Wong, {Flora Y.}",
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Dobutamine treatment reduces inflammation in the preterm fetal sheep brain exposed to acute hypoxia. / Brew, Nadine; Nakamura, Shinji; Hale, Nadia; Azhan, Aminath; Davies, Grace I.; Nitsos, Ilias; Miller, Suzanne L.; Walker, David W.; Wong, Flora Y.

In: Pediatric Research, Vol. 84, No. 3, 01.09.2018, p. 442-450.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Dobutamine treatment reduces inflammation in the preterm fetal sheep brain exposed to acute hypoxia

AU - Brew, Nadine

AU - Nakamura, Shinji

AU - Hale, Nadia

AU - Azhan, Aminath

AU - Davies, Grace I.

AU - Nitsos, Ilias

AU - Miller, Suzanne L.

AU - Walker, David W.

AU - Wong, Flora Y.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background: Impaired cerebral autoregulation in preterm infants makes circulatory management important to avoid cerebral hypoxic–ischemic injury. Dobutamine is frequently used as inotropic treatment in preterm neonates, but its effects on the brain exposed to cerebral hypoxia are unknown. We hypothesized that dobutamine would protect the immature brain from cerebral hypoxic injury. Methods: In preterm (0.6 gestation) fetal sheep, dobutamine (Dob, 10 μg/kg/min) or saline (Sal) was infused intravenously for 74 h. Two hours after the beginning of the infusion, umbilical cord occlusion (UCO) was performed to produce fetal asphyxia (Sal+UCO: n = 9, Dob+UCO: n = 7), or sham occlusion (Sal+sham: n = 7, Dob+sham: n = 6) was performed. Brains were collected 72 h later for neuropathology. Results: Dobutamine did not induce cerebral changes in the sham UCO group. UCO increased apoptosis and microglia density in white matter, hippocampus, and caudate nucleus, and astrocyte density in the caudate nucleus. Dobutamine commenced before UCO reduced microglia infiltration in the white matter, and microglial and astrocyte density in the caudate. Conclusion: In preterm hypoxia-induced brain injury, dobutamine decreases neuroinflammation in the white matter and caudate, and reduces astrogliosis in the caudate. Early administration of dobutamine in preterm infants for cardiovascular stabilization appears safe and may be neuroprotective against unforeseeable cerebral hypoxic injury.

AB - Background: Impaired cerebral autoregulation in preterm infants makes circulatory management important to avoid cerebral hypoxic–ischemic injury. Dobutamine is frequently used as inotropic treatment in preterm neonates, but its effects on the brain exposed to cerebral hypoxia are unknown. We hypothesized that dobutamine would protect the immature brain from cerebral hypoxic injury. Methods: In preterm (0.6 gestation) fetal sheep, dobutamine (Dob, 10 μg/kg/min) or saline (Sal) was infused intravenously for 74 h. Two hours after the beginning of the infusion, umbilical cord occlusion (UCO) was performed to produce fetal asphyxia (Sal+UCO: n = 9, Dob+UCO: n = 7), or sham occlusion (Sal+sham: n = 7, Dob+sham: n = 6) was performed. Brains were collected 72 h later for neuropathology. Results: Dobutamine did not induce cerebral changes in the sham UCO group. UCO increased apoptosis and microglia density in white matter, hippocampus, and caudate nucleus, and astrocyte density in the caudate nucleus. Dobutamine commenced before UCO reduced microglia infiltration in the white matter, and microglial and astrocyte density in the caudate. Conclusion: In preterm hypoxia-induced brain injury, dobutamine decreases neuroinflammation in the white matter and caudate, and reduces astrogliosis in the caudate. Early administration of dobutamine in preterm infants for cardiovascular stabilization appears safe and may be neuroprotective against unforeseeable cerebral hypoxic injury.

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JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

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