Repeated mild traumatic brain injury results in long-term white-matter disruption.
Mild traumatic brain injury (mTBI) is an increasing public health concern as repetitive injuries can exacerbate existing neuropathology and result in increased neurologic deficits. In contrast to other models of repeated mTBI (rmTBI), our study focused on long-term white-matter abnormalities after bilateral mTBIs induced 7 days apart. A controlled cortical impact (CCI) was used to induce an initial mTBI to the right cortex of Single and rmTBI Sprague Dawley rats, followed by a second injury to the left cortex of rmTBI animals. Shams received only a craniectomy. Ex vivo diffusion tensor imaging (DTI), transmission electron microscopy (TEM), and histology were performed on the anterior corpus callosum at 60 days after injury. The rmTBI animals showed a significant bilateral increase in radial diffusivity (myelin), while only modest changes in axial diffusivity (axonal) were seen between the groups. Further, the rmTBI group showed an increased g-ratio and axon caliber in addition to myelin sheath abnormalities using TEM. Our DTI results indicate ongoing myelin changes, while the TEM data show continuing axonal changes at 60 days after rmTBI. These data suggest that bilateral rmTBI induced 7 days apart leads to progressive alterations in white matter that are not observed after a single mTBI.
Cell, Molecular and Developmental Biology Program, University of California, Riverside, California, USA.
Virginia
V
Donovan
School of Medicine, Loma Linda University, Loma Linda, California, USA.
Claudia
C
Kim
School of Medicine, Loma Linda University, Loma Linda, California, USA.
Ariana K
AK
Anugerah
Department of Pediatrics, Loma Linda University, Loma Linda, California, USA.
Jacqueline S
JS
Coats
Department of Radiology, Loma Linda University, Loma Linda, California, USA.
Udochuwku
U
Oyoyo
Department of Pediatrics, Loma Linda University, Loma Linda, California, USA.
Andrea C
AC
Pardo
1] Cell, Molecular and Developmental Biology Program, University of California, Riverside, California, USA [2] Department of Pediatrics, Loma Linda University, Loma Linda, California, USA.
Andre
A
Obenaus
D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D001930:Brain Injuries / Q000473:pathology*; D003337:Corpus Callosum / Q000648:ultrastructure*; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D008297:Male; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D015599:Trauma Severity Indices