Anzari Atik1, Jeanie Cheong2, Richard Harding1, Sandra Rees3, Robert De Matteo1, Mary Tolcos4. 1. Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia. 2. 1] Department of Neonatal Services, Royal Women's Hospital, Victorian Infant Brain Studies, Murdoch Children's Research Institute, University of Melbourne, Melbourne, Victoria, Australia [2] Department of Obstetrics and Gynecology, University of Melbourne, Melbourne, Victoria, Australia. 3. Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia. 4. The Ritchie Centre, MIMR-PHI Institute of Medical Research and Monash University, Clayton, Victoria, Australia.
Abstract
BACKGROUND: Caffeine is widely used to treat apnea of prematurity, but the standard dosing regimen is not always sufficient to prevent apnea. Before higher doses of caffeine can be used, their effects on the immature brain need to be carefully evaluated. Our aim was to determine the impact of daily high-dose caffeine administration on the developing white matter of the immature ovine brain. METHODS: High-dose caffeine (25 mg/kg caffeine base loading dose; 20 mg/kg daily maintenance dose; n = 9) or saline (n = 8) were administered to pregnant sheep from 0.7 to 0.8 of term, equivalent to approximately 27-34 wk in humans. At 0.8 of term, the white and gray matter were assessed histologically and immunohistochemically. RESULTS: Daily caffeine administration led to peak caffeine concentration of 32 mg/l in fetal plasma at 1 h, followed by a gradual decline, with no effects on mean arterial pressure and heart rate. Initial caffeine exposure led to transient, mild alkalosis in the fetus but did not alter oxygenation. At necropsy, there was no effect of daily high-dose caffeine on brain weight, oligodendrocyte density, myelination, axonal integrity, microgliosis, astrogliosis, apoptosis, or neuronal density. CONCLUSION: Daily high-dose caffeine administration does not appear to adversely affect the developing white matter at the microstructural level.
BACKGROUND:Caffeine is widely used to treat apnea of prematurity, but the standard dosing regimen is not always sufficient to prevent apnea. Before higher doses of caffeine can be used, their effects on the immature brain need to be carefully evaluated. Our aim was to determine the impact of daily high-dose caffeine administration on the developing white matter of the immature ovine brain. METHODS: High-dose caffeine (25 mg/kg caffeine base loading dose; 20 mg/kg daily maintenance dose; n = 9) or saline (n = 8) were administered to pregnant sheep from 0.7 to 0.8 of term, equivalent to approximately 27-34 wk in humans. At 0.8 of term, the white and gray matter were assessed histologically and immunohistochemically. RESULTS: Daily caffeine administration led to peak caffeine concentration of 32 mg/l in fetal plasma at 1 h, followed by a gradual decline, with no effects on mean arterial pressure and heart rate. Initial caffeine exposure led to transient, mild alkalosis in the fetus but did not alter oxygenation. At necropsy, there was no effect of daily high-dose caffeine on brain weight, oligodendrocyte density, myelination, axonal integrity, microgliosis, astrogliosis, apoptosis, or neuronal density. CONCLUSION: Daily high-dose caffeine administration does not appear to adversely affect the developing white matter at the microstructural level.
Authors: Lennart Van der Veeken; Susanne Grönlund; Erik Gerdtsson; Bo Holmqvist; Jan Deprest; David Ley; Matteo Bruschettini Journal: Pediatr Res Date: 2019-12-07 Impact factor: 3.756
Authors: Joshua O Owolabi; Kehinde A Adefule; Philemon D Shallie; Oluseyi S Fabiyi; Sunday Y Olatunji; John Afeez Olanrewaju; Testimony P Ajibade; Samson Oyewumi; Philip O Ogunnaike Journal: Metab Brain Dis Date: 2021-08-30 Impact factor: 3.584
Authors: Samantha K Barton; Annie R A McDougall; Jacqueline M Melville; Timothy J M Moss; Valerie A Zahra; Tammy Lim; Kelly J Crossley; Graeme R Polglase; Mary Tolcos Journal: J Physiol Date: 2015-10-08 Impact factor: 5.182
Authors: Samantha K Barton; Timothy J M Moss; Stuart B Hooper; Kelly J Crossley; Andrew W Gill; Martin Kluckow; Valerie Zahra; Flora Y Wong; Gerhard Pichler; Robert Galinsky; Suzanne L Miller; Mary Tolcos; Graeme R Polglase Journal: PLoS One Date: 2014-11-07 Impact factor: 3.240
Authors: Menuka Pallebage-Gamarallage; Sean Foxley; Ricarda A L Menke; Istvan N Huszar; Mark Jenkinson; Benjamin C Tendler; Chaoyue Wang; Saad Jbabdi; Martin R Turner; Karla L Miller; Olaf Ansorge Journal: BMC Neurosci Date: 2018-03-13 Impact factor: 3.288
Authors: Anzari Atik; Robert De Matteo; Meghan Boomgardt; Sandra Rees; Richard Harding; Jeanie Cheong; Shreya Rana; Kelly Crossley; Mary Tolcos Journal: Front Physiol Date: 2019-08-02 Impact factor: 4.566
Authors: Vanesa Stojanovska; Anzari Atik; Ilias Nitsos; Béatrice Skiöld; Samantha K Barton; Valerie A Zahra; Karyn Rodgers; Stuart B Hooper; Graeme R Polglase; Robert Galinsky Journal: Front Pediatr Date: 2018-06-15 Impact factor: 3.418