Magnesium sulfate reduces EEG activity but is not neuroprotective after asphyxia in preterm fetal sheep.
Magnesium sulfate is now widely recommended for neuroprotection for preterm birth; however, this has been controversial because there is little evidence that magnesium sulfate is neuroprotective. Preterm fetal sheep (104 days gestation; term is 147 days) were randomly assigned to receive sham occlusion (n = 7), i.v. magnesium sulfate (n = 10) or saline (n = 8) starting 24 h before asphyxia until 24 h after asphyxia. Sheep were killed 72 h after asphyxia. Magnesium sulfate infusion reduced electroencephalograph power and fetal movements before asphyxia. Magnesium sulfate infusion did not affect electroencephalograph power during recovery, but was associated with marked reduction of the post-asphyxial seizure burden (mean ± SD: 34 ± 18 min vs. 107 ± 74 min, P < 0.05). Magnesium sulfate infusion did not affect subcortical neuronal loss. In the intragyral and periventricular white matter, magnesium sulfate was associated with reduced numbers of all (Olig-2+ve) oligodendrocytes in the intragyral (125 ± 23 vs. 163 ± 38 cells/field) and periventricular white matter (162 ± 39 vs. 209 ± 44 cells/field) compared to saline-treated controls ( P < 0.05), but no effect on microglial induction or astrogliosis. In conclusion, a clinically comparable dose of magnesium sulfate showed significant anticonvulsant effects after asphyxia in preterm fetal sheep, but did not reduce asphyxia-induced brain injury and exacerbated loss of oligodendrocytes.
1 Department of Physiology, University of Auckland, Auckland, New Zealand.|2 The Ritchie Centre, the Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Robert
R
Galinsky
1 Department of Physiology, University of Auckland, Auckland, New Zealand.
Vittoria
V
Draghi
1 Department of Physiology, University of Auckland, Auckland, New Zealand.
Guido
G
Wassink
1 Department of Physiology, University of Auckland, Auckland, New Zealand.
Joanne O
JO
Davidson
1 Department of Physiology, University of Auckland, Auckland, New Zealand.
Paul P
PP
Drury
1 Department of Physiology, University of Auckland, Auckland, New Zealand.
Christopher A
CA
Lear
1 Department of Physiology, University of Auckland, Auckland, New Zealand.
Alistair J
AJ
Gunn
1 Department of Physiology, University of Auckland, Auckland, New Zealand.
Laura
L
Bennet
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects*; D005311:Fetal Hypoxia / Q000188:drug therapy* / Q000196:embryology / Q000473:pathology; D005865:Gestational Age; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D012756:Sheep
D018696:Neuroprotective Agents; D008278:Magnesium Sulfate
Magnesium sulfate; asphyxia; brain; neuroprotection; preterm fetus