Jose F. Abisambra (United States of America)
University of Florida Department of NeuroscienceAuthor Of 1 Presentation
REPETITIVE MILD TRAUMATIC BRAIN INJURY IMPAIRS RESTING STATE FMRI CONNECTIVITY AND ALTERS PROTEIN PROFILES IN SIGNALING NETWORKS
Abstract
Aims
Repetitive mild traumatic brain injury (rmTBI) substantially increases risk for development of Alzheimer’s disease later in life. A major challenge in developing diagnostics and treatments for rmTBI before the onset of chronic neurodegenerative disorders, are the fundamental knowledge gaps that explain how they promote brain dysfunction. It is critical and urgent to understand the neuropathological and functional consequences of rmTBI to develop effective therapeutic strategies. In this study, we sought to define the extent of altered brain functional connectivity (FC) and levels of neuropathological markers after rmTBI.
Methods
We performed two impacts 24h apart in C57BL/6J (~2.5-3mo) mice using the closed head injury model of engineered rotational acceleration (CHIMERA). At 5-6 days post-injury (dpi), we measured changes in brain volume and FC using T2-weighted images, resting-state functional MRI (rsfMRI), and graph theory analyses; diffusion tensor imaging (DTI) assessed white matter integrity. At 7dpi, we measured levels of disease-associated protein markers in different brain regions using NanoString-GeoMx digital spatial protein profiling (DSP).
Results
The rsfMRI data revealed aberrant FC in areas that process somatosensory inputs; DTI revealed significant alterations in the optic tract and hippocampus. DSP showed significant changes in the levels of numerous proteins in distinct brain regions: phospho-tau species and glial proteins in the optic tract, the neuroinflammatory protein GPNMB and cell proliferation marker Ki-67 in the thalamus, and myelin basic protein in the somatosensory area.
Conclusions
Our data suggest that rmTBI alters brain connectivity and protein profiles in specific brain areas, thereby highlighting the underlying complexity of rmTBI mechanisms.
Presenter of 1 Presentation
REPETITIVE MILD TRAUMATIC BRAIN INJURY IMPAIRS RESTING STATE FMRI CONNECTIVITY AND ALTERS PROTEIN PROFILES IN SIGNALING NETWORKS
Abstract
Aims
Repetitive mild traumatic brain injury (rmTBI) substantially increases risk for development of Alzheimer’s disease later in life. A major challenge in developing diagnostics and treatments for rmTBI before the onset of chronic neurodegenerative disorders, are the fundamental knowledge gaps that explain how they promote brain dysfunction. It is critical and urgent to understand the neuropathological and functional consequences of rmTBI to develop effective therapeutic strategies. In this study, we sought to define the extent of altered brain functional connectivity (FC) and levels of neuropathological markers after rmTBI.
Methods
We performed two impacts 24h apart in C57BL/6J (~2.5-3mo) mice using the closed head injury model of engineered rotational acceleration (CHIMERA). At 5-6 days post-injury (dpi), we measured changes in brain volume and FC using T2-weighted images, resting-state functional MRI (rsfMRI), and graph theory analyses; diffusion tensor imaging (DTI) assessed white matter integrity. At 7dpi, we measured levels of disease-associated protein markers in different brain regions using NanoString-GeoMx digital spatial protein profiling (DSP).
Results
The rsfMRI data revealed aberrant FC in areas that process somatosensory inputs; DTI revealed significant alterations in the optic tract and hippocampus. DSP showed significant changes in the levels of numerous proteins in distinct brain regions: phospho-tau species and glial proteins in the optic tract, the neuroinflammatory protein GPNMB and cell proliferation marker Ki-67 in the thalamus, and myelin basic protein in the somatosensory area.
Conclusions
Our data suggest that rmTBI alters brain connectivity and protein profiles in specific brain areas, thereby highlighting the underlying complexity of rmTBI mechanisms.