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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Syst. Neurosci. | doi: 10.3389/fnsys.2019.00034

Neuropathological Changes following Single or Repetitive Mild TBI

 Praveen Kulkarni1, Thomas Morrison1, Xuezhu Cai1, Sade Iriah1,  Neal G. Simon2, Julia Sabrick1,  Lucas Neuroth1 and  Craig F. Ferris3, 4*
  • 1Department of Psychology, College of Science, Northeastern University, United States
  • 2Department of Biological Sciences, College of Arts and Sciences, Lehigh University, United States
  • 3Northeastern University, United States
  • 4Department of Psychology and Pharmaceutical Sciences, Center for Translational NeuroImaging, Northeastern University, United States

Objectives: To test the hypothesis that there are differences in neuroradiological measures between single and repeated mild TBI using multimodal MRI.
Methods: A closed-head momentum exchange model was used to produce one or three mild head injuries in young adult male rats as compared to non-injured, age and weight-matched controls. Six-seven weeks post-injury, rats were studied for deficits in cognitive and motor function. Seven-eight weeks post-injury changes in brain anatomy and function were evaluated through analysis of high resolution T2 weighted images, resting state BOLD functional connectivity, and diffusion weighted imaging with quantitative anisotropy.
Results: Head injuries occurred without skull fracture or signs of intracranial bleeding or contusion. There were no significant differences in cognitive or motors behaviors between experimental groups. With a single mild hit, the affected areas were limited to the caudate/putamen and central amygdala. Rats hit three times showed altered diffusivity in white matter tracts, basal ganglia, central amygdala, brainstem, and cerebellum. Comparing three hits to one hit showed a similar pattern of change underscoring a dose effect of repeated head injury on the brainstem and cerebellum. Disruption of functional connectivity was pronounced with three mild hits. The midbrain dopamine system, hippocampus, and brainstem/cerebellum showed hypoconnectivity. Interestingly, rats exposed to one hit showed enhanced functional connectivity (or hyperconnectivity) across brain sites, particularly between the olfactory system and the cerebellum.
Interpretation: Neuroradiological evidence of altered brain structure and function, particularly in striatal and midbrain dopaminergic areas, persists long after mild repetitive head injury. These changes may serve as biomarkers of neurodegeneration and risk for dementia later in life.

Keywords: Parkinson ’s disease, Dopamine, Dementia, hyperconnectivity, microglia activation, Cerebellum, Suprachiasmatic nucleus (SCN), olfactory system diseases

Received: 15 Dec 2018; Accepted: 10 Jul 2019.

Edited by:

James W. Grau, Texas A&M University, United States

Reviewed by:

Rebekah Mannix, Boston Children's Hospital, Harvard Medical School, United States
Sandy R. Shultz, Monash University, Australia
Ramesh Raghupathi, College of Medicine, Drexel University, United States  

Copyright: © 2019 Kulkarni, Morrison, Cai, Iriah, Simon, Sabrick, Neuroth and Ferris. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Craig F. Ferris, Northeastern University, Boston, United States,