Maternal hypoxia during pregnancy induces fetal neurodevelopmental brain damage: partial protection by magnesium sulfate.
Fetal low brain oxygenation may be an outcome of maternal complications during pregnancy and is associated with increased risk of cerebral palsy and periventricular leukomalacia in newborns. One treatment used for prevention of fetal brain damage is maternal treatment with MgSO(4). Although this treatment is indicated to reduce the risk of cerebral palsy in newborns, its use remains controversial. We have shown previously that pretreatment with MgSO(4) in a mouse model of maternal hypoxia prevented a delay in the development of motor reflexes induced by hypoxia. We demonstrate here that pretreatment with MgSO(4) reduces hypoxia-induced motor disabilities in adult offspring. This effect is associated with histologic protection of the Purkinje cells in the cerebellum and stabilization of brain-derived neurotrophic factor (BDNF) levels in the cerebellum. MgSO(4) did not prevent the reduction in cerebral cortex cell density and cell size induced by maternal hypoxia, however, nor did it interfere with the modulation of BDNF and nerve growth factor (NGF) expression in the cerebral cortex. MgSO(4) pretreatment also prevented the impairment of short-term memory (30 min, P < 0.05) but not long-term memory (7 days). Nevertheless, maternal pretreatment with MgSO(4) reduced CA1 cell layer width and induced alterations in both NGF and BDNF in the hippocampus. These results support the prophylactic effect of MgSO(4) against motor disabilities; however, they may also indicate possible harmful effects on the cerebral cortex and hippocampus.
Golan
H
H
Department of Developmental Molecular Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. havag@bgumail.bgu.ac.il
Kashtuzki
I
I
Hallak
M
M
Sorokin
Y
Y
Huleihel
M
M
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use*; D001259:Ataxia / Q000503:physiopathology; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D000860:Hypoxia / Q000150:complications* / Q000473:pathology; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D020932:Nerve Growth Factor / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011597:Psychomotor Performance / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects
D000927:Anticonvulsants; D019208:Brain-Derived Neurotrophic Factor; D008278:Magnesium Sulfate; D020932:Nerve Growth Factor