Magnesium sulfate reduces inflammation-associated brain injury in fetal mice.
OBJECTIVE
The purpose of this study was to investigate whether magnesium sulfate (MgSO(4)) prevents fetal brain injury in inflammation-associated preterm birth (PTB).


METHODS
In a mouse model of PTB, mice exposed to lipopolysaccharide (LPS) or normal saline (NS) by intrauterine injection were randomized to intraperitoneal treatment with MgSO(4) or NS [corrected]. From the 4 treatment groups (NS + NS; LPS + NS; LPS + MgSO(4); and NS + MgSO(4)), fetal brains were collected for quantitative polymerase chain reaction studies and primary neuronal cultures. Messenger RNA expression of cytokines, cell death, and markers of neuronal and glial differentiation were assessed. Immunocytochemistry and confocal microscopy were performed.


RESULTS
There was no difference between the LPS + NS and LPS + MgSO(4) groups in the expression of proinflammatory cytokines, cell death markers, and markers of prooligodendrocyte and astrocyte development (P > .05 for all). Neuronal cultures from the LPS + NS group demonstrated morphologic changes; this neuronal injury was prevented by MgSO(4) (P < .001).


CONCLUSIONS
Amelioration of neuronal injury in inflammation-associated PTB may be a key mechanism by which MgSO(4) prevents cerebral palsy.
Burd
Irina
I
Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania, 1353 Biomedical Research Bldg. II/III, 421 Curie Blvd., Philadelphia, PA 19104-6142, USA. irina.burd@uphs.upenn.edu
Breen
Kelsey
K
Friedman
Alexander
A
Chai
Jinghua
J
Elovitz
Michal A
MA
D000818:Animals; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008278:Magnesium Sulfate / Q000494:pharmacology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D023421:Models, Animal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D015149:Tocolytic Agents / Q000494:pharmacology*
D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D008070:Lipopolysaccharides; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D012333:RNA, Messenger; D015149:Tocolytic Agents; D008278:Magnesium Sulfate; D020169:Caspases