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Magnesium induces preconditioning of the neonatal brain via profound mitochondrial protection.

Journal article
Authors Gabriella Koning
Anna-Lena Leverin
Syam Nair
Leslie Schwendimann
C. Joakim Ek
Ylva Carlsson
Pierre Gressens
Claire Thornton
Xiaoyang Wang
Carina Mallard
Henrik Hagberg
Published in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Volume 39
Issue 6
Pages 1038-1055
ISSN 1559-7016
Publication year 2019
Published at Institute of Neuroscience and Physiology
Institute of Clinical Sciences, Department of Obstetrics and Gynecology
Pages 1038-1055
Language en
Subject categories Pediatrics


Magnesium sulphate (MgSO4) given to women in preterm labor reduces cerebral palsy in their offspring but the mechanism behind this protection is unclear, limiting its effective, safe clinical implementation. Previous studies suggest that MgSO4 is not neuroprotective if administered during or after the insult, so we hypothesised that MgSO4 induces preconditioning in the immature brain. Therefore, we administered MgSO4 at various time-points before/after unilateral hypoxia-ischemia (HI) in seven-day-old rats. We found that MgSO4 treatment administered as a bolus between 6 days and 12 h prior to HI markedly reduced the brain injury, with maximal protection achieved by 1.1 mg/g MgSO4 administered 24 h before HI. As serum magnesium levels returned to baseline before the induction of HI, we ascribed this reduction in brain injury to preconditioning. Cerebral blood flow was unaffected, but mRNAs/miRNAs involved in mitochondrial function and metabolism were modulated by MgSO4. Metabolomic analysis (H+-NMR) disclosed that MgSO4 attenuated HI-induced increases in succinate and prevented depletion of high-energy phosphates. MgSO4 pretreatment preserved mitochondrial respiration, reducing ROS production and inflammation after HI. Therefore, we propose that MgSO4 evokes preconditioning via induction of mitochondrial resistance and attenuation of inflammation.

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