title: Repetitive Model of Mild Traumatic Brain Injury Produces Cortical Abnormalities Detectable by Magnetic Resonance Diffusion Imaging, Histopathology, and Behavior.
abstract: Noninvasive detection of mild traumatic brain injury (mTBI) is important for evaluating acute through chronic effects of head injuries, particularly after repetitive impacts. To better detect abnormalities from mTBI, we performed longitudinal studies (baseline, 3, 6, and 42 days) using magnetic resonance diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) in adult mice after repetitive mTBI (r-mTBI; daily × 5) or sham procedure. This r-mTBI produced righting reflex delay and was first characterized in the corpus callosum to demonstrate low levels of axon damage, astrogliosis, and microglial activation, without microhemorrhages. High-resolution DTI-DKI was then combined with post-imaging pathological validation along with behavioral assessments targeted for the impact regions. In the corpus callosum, only DTI fractional anisotropy at 42 days showed significant change post-injury. Conversely, cortical regions under the impact site (M1-M2, anterior cingulate) had reduced axial diffusivity (AD) at all time points with a corresponding increase in axial kurtosis (Ka) at 6 days. Post-imaging neuropathology showed microglial activation in both the corpus callosum and cortex at 42 days after r-mTBI. Increased cortical microglial activation correlated with decreased cortical AD after r-mTBI (r = -0.853; n = 5). Using Thy1-YFP-16 mice to fluorescently label neuronal cell bodies and processes revealed low levels of axon damage in the cortex after r-mTBI. Finally, r-mTBI produced social deficits consistent with the function of this anterior cingulate region of cortex. Overall, vulnerability of cortical regions is demonstrated after mild repetitive injury, with underlying differences of DTI and DKI, microglial activation, and behavioral deficits.
authors: 1 Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland.|2 Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors: Fengshan
authors: F
authors: Yu
authors: 1 Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland.|5 Department of Psychiatry, University of Maryland School of Medicine , Baltimore, Maryland.
authors: Dinesh K
authors: DK
authors: Shukla
authors: 1 Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland.|2 Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, Maryland.|3 Program in Neuroscience, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors: Regina C
authors: RC
authors: Armstrong
authors: 1 Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland.|3 Program in Neuroscience, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors: Christina M
authors: CM
authors: Marion
authors: 1 Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland.|2 Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors: Kryslaine L
authors: KL
authors: Radomski
authors: 1 Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland.|6 Department of Radiology, University of New Mexico , Albuquerque, New Mexico .
authors: Reed G
authors: RG
authors: Selwyn
authors: 1 Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland.|4 Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors: Bernard J
authors: BJ
authors: Dardzinski
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D001522:Behavior, Animal / Q000502:physiology*; D001924:Brain Concussion / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology*; D003337:Corpus Callosum / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology*
keywords: Thy1-YFP; concussion; diffusion kurtosis imaging; diffusion tensor imaging; microglia