Oligodendrocyte lineage and subventricular zone response to traumatic axonal injury in the corpus callosum.
Traumatic brain injury frequently causes traumatic axonal injury (TAI) in white matter tracts. Experimental TAI in the corpus callosum of adult mice was used to examine the effects on oligodendrocyte lineage cells and myelin in conjunction with neuroimaging. The injury targeted the corpus callosum over the subventricular zone, a source of neural stem/progenitor cells. Traumatic axonal injury was produced in the rostral body of the corpus callosum by impact onto the skull at the bregma. During the first week after injury, magnetic resonance diffusion tensor imaging showed that axial diffusivity decreased in the corpus callosum and that corresponding regions exhibited significant axon damage accompanied by hypertrophic microglia and reactive astrocytes. Oligodendrocyte progenitor proliferation increased in the subventricular zone and corpus callosum. Oligodendrocytes in the corpus callosum shifted toward upregulation of myelin gene transcription. Plp/CreER(T):R26IAP reporter mice showed normal reporter labeling of myelin sheaths 0 to 2 days after injury but labeling was increased between 2 and 7 days after injury. Electron microscopy revealed axon degeneration, demyelination, and redundant myelin figures. These findings expand the cell types and responses to white matter injuries that inform diffusion tensor imaging evaluation and identify pivotal white matter changes after TAI that may affect axon vulnerability vs. recovery after brain injury.
From the Program in Molecular and Cell Biology (GMS, RCA), Department of Anatomy (GMS, AJM, RCA), Physiology and Genetics, Center for Neuroscience and Regenerative Medicine (GMS, AJM, NK, HT, RS, RCA), Department of Radiology (HT, RS), Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Radiology (YW, S-KS), Washington University, St. Louis, Missouri; and Department of Internal Medicine (NK), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Genevieve M
GM
Sullivan
Amanda J
AJ
Mierzwa
Naruchorn
N
Kijpaisalratana
Haiying
H
Tang
Yong
Y
Wang
Sheng-Kwei
SK
Song
Reed
R
Selwyn
Regina C
RC
Armstrong
D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D000941:Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000473:pathology*; D003337:Corpus Callosum / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D003430:Cross-Sectional Studies; D020833:Diffuse Axonal Injury / Q000473:pathology* / Q000503:physiopathology; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009836:Oligodendroglia / Q000502:physiology* / Q000648:ultrastructure; D011509:Proteoglycans / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D011509:Proteoglycans; D011960:Receptors, Estrogen; D000099216:Chondroitin Sulfate Proteoglycan 4