Multimodal MRI Imaging of Apoptosis-Triggered Microstructural Alterations in the Postnatal Cerebral Cortex.
Prematurely born children often develop neurodevelopmental delay that has been correlated with reduced growth and microstructural alterations in the cerebral cortex. Much research has focused on apoptotic neuronal cell death as a key neuropathological features following preterm brain injuries. How scattered apoptotic death of neurons may contribute to microstructural alterations remains unknown. The present study investigated in a rat model the effects of targeted neuronal apoptosis on cortical microstructure using in vivo MRI imaging combined with neuronal reconstruction and histological analysis. We describe that mild, targeted death of layer IV neurons in the developing rat cortex induces MRI-defined metabolic and microstructural alterations including increased cortical fractional anisotropy. Delayed architectural modifications in cortical gray matter and myelin abnormalities in the subcortical white matter such as hypomyelination and microglia activation follow the acute phase of neuronal death and axonal degeneration. These results establish the link between mild cortical apoptosis and MRI-defined microstructure changes that are reminiscent to those previously observed in preterm babies.
Department of Neurosciences, University of Geneva Medical School, Geneva, Switzerland.
Volodymyr
V
Petrenko
Division of Child Growth & Development, Department of Pediatrics, University of Geneva, Geneva, Switzerland.|Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Yohan
Y
van de Looij
Department of Neurosciences, University of Geneva Medical School, Geneva, Switzerland.
Jevgenia
J
Mihhailova
Department of Neurosciences, University of Geneva Medical School, Geneva, Switzerland.
Patrick
P
Salmon
Division of Child Growth & Development, Department of Pediatrics, University of Geneva, Geneva, Switzerland.
Petra S
PS
Hüppi
Division of Child Growth & Development, Department of Pediatrics, University of Geneva, Geneva, Switzerland.
Stéphane V
SV
Sizonenko
Department of Neurosciences, University of Geneva Medical School, Geneva, Switzerland.
Jozsef Z
JZ
Kiss
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000000981:diagnostic imaging / Q000254:growth & development; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004167:Diphtheria Toxin / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001224:Aspartic Acid; D002135:Calcium-Binding Proteins; D004167:Diphtheria Toxin; D005904:Glial Fibrillary Acidic Protein; D005974:Glutamate-Ammonia Ligase; D018698:Glutamic Acid; D005973:Glutamine; D008164:Luminescent Proteins; D008840:Microfilament Proteins; D010751:Phosphopyruvate Hydratase; C491049:Aif1 protein, mouse; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C000179:N-acetylaspartate
apoptosis; brain development; cortical plasticity; magnetic resonance imaging; white matter injury