Multimodal Magnetic Resonance Imaging with Mild Repetitive Head Injury in Awake Rats: Modeling the Human Experience and Clinical Condition
Nicole Bens1 · Arnold Chang1 · Richard Ortiz2 · Joshua Leaston3 · Praveen Kulkarni1 · Rosemarie Hightower1 · Sophia Prom1 · Nicholas O’Hare4 · Eno Ebong4,5 · Craig F. Ferris1,61 Center for Translational Neuroimaging, Northeastern University, Boston, MA 02115, USA
2 Department of Psychology, Northern Illinois Univ, DeKalb, IL 60112, USA
3 Stanford Medical School, Palo Alto, CA 94301, USA
4 Department of Bioengineering, Northeastern University, Boston, MA 02115, USA
5 Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA
6 Departments of Psychology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA
Abstract
Mild repetitive head injury is a serious health problem with long-term negative consequences. Changes in brain neurobiology were assessed with MRI in a model of head injury designed to reflect the human experience. Rats were maintained on a reverse light-dark cycle and head impacted daily at 24 h intervals over three days while fully awake under red light illumination. There was no neuroradiological evidence of brain damage. Rats were imaged for changes in blood brain barrier permeability, edema and gray matter microarchitecture, and resting state functional connectivity. Data were registered to a 3D MRI rat atlas with 173 segmented brain areas providing site-specific information on each imaging modality. Changes in BBB permeability were minimal and localized to the hippocampus and cerebellum. There was evidence of cytotoxic edema in the basal ganglia, thalamus, and cerebellum. There was a global decrease in connectivity and an increase in gliosis in the thalamus, cerebellum, and hippocampus. This study shows a sequelae of neuropathology caused by mild repetitive head injury that is commonly observed in clinical practice using MRI in patients. As such, it may serve as a model for testing the efficacy of new therapeutics using any or all of the measures as biomarkers to assess drug efficacy.
Keywords
Astrogliosis; Cerebral small vessel disease; Concussion; Ferumoxytol
