Delayed white matter injury in a murine model of shaken baby syndrome.
Shaken baby syndrome, a rotational acceleration injury, is most common between 3 and 6 months of age and causes death in about 10 to 40% of cases and permanent neurological abnormalities in survivors. We developed a mouse model of shaken baby syndrome to investigate the pathophysiological mechanisms underlying the brain damage. Eight-day-old mouse pups were shaken for 15 seconds on a rotating shaker. Animals were sacrificed at different ages after shaking and brains were processed for histology. In 31-day-old pups, mortality was 27%, and 75% of survivors had focal brain lesions consisting of hemorrhagic or cystic lesions of the periventricular white matter, corpus callosum, and brainstem and cerebellar white matter. Hemorrhagic lesions were evident from postnatal day 13, and cysts developed gradually between days 15 and 31. All shaken animals, with or without focal lesions, had thinning of the hemispheric white matter, which was significant on day 31 but not earlier. Fragmented DNA labeling revealed a significant increase in cell death in the periventricular white matter, on days 9 and 13. White matter damage was reduced by pre-treatment with the NMDA receptor antagonist MK-801. This study showed that shaking immature mice produced white matter injury mimicking several aspects of human shaken baby syndrome and provided evidence that excess release of glutamate plays a role in the pathophysiology of the lesions.
Bonnier
C
C
Service de Neurologie Pédiatrique, University of Louvain Medical School, Bruxelles, Belgium.
Mesplès
B
B
Carpentier
S
S
Henin
D
D
Gressens
P
P
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology*; D001933:Brain Stem / Q000293:injuries / Q000473:pathology; D016923:Cell Death; D002531:Cerebellum / Q000293:injuries / Q000473:pathology; D003337:Corpus Callosum / Q000293:injuries / Q000473:pathology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D038642:Shaken Baby Syndrome / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate