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Fixed Time-Point Analysis Reveals Repetitive Mild Traumatic Brain Injury Effects on Resting State Functional Magnetic

Ravi Sakthivel1,2,3, Marangelie Criado-Marrero1,2,3, Daylin Barroso1,2,3

  • 1Center for Translational Research in Neurodegenerative Disease (CTRND), University of Florida, Gainesville, Florida, USA.

Journal of Neurotrauma
|April 13, 2023
PubMed
Summary
This summary is machine-generated.

Repetitive mild traumatic brain injuries (rmTBIs) alter brain connectivity and protein levels, even in areas without apparent damage. Understanding these changes is crucial for developing treatments for neurodegenerative disorders following rmTBI.

Keywords:
CHIMERAdiffusion tensor imagingmicrogliaoptic tractrepetitive mild TBIresting state fMRIthalamus

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Area of Science:

  • Neuroscience
  • Neurology
  • Biomedical Engineering

Background:

  • Repetitive mild traumatic brain injuries (rmTBIs) are linked to neurodegenerative disorders.
  • Knowledge gaps exist regarding the molecular mechanisms underlying rmTBI-induced neurodegeneration.
  • Understanding neuropathological and functional consequences of rmTBI is vital for therapeutic development.

Purpose of the Study:

  • To investigate the neuropathological and functional consequences of rmTBI.
  • To identify molecular mechanisms driving neurodegeneration after rmTBI.
  • To analyze brain connectivity and protein changes post-rmTBI.

Main Methods:

  • Utilized the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA).
  • Performed brain volume, diffusion tensor imaging, and resting-state functional MRI with graph theory and functional connectivity analyses.
  • Analyzed gliosis markers and used NanoString-GeoMx for digital-spatial protein profiling of neurodegenerative disease-associated proteins.

Main Results:

  • Aberrant thalamic connectivity changes were observed, independent of microstructural damage or neuroinflammation.
  • Distinct changes in protein levels, including total and phospho-tau species and cell proliferation markers, were identified.
  • rmTBI significantly altered brain functional connectivity and induced protein changes in morphologically intact brain areas.

Conclusions:

  • rmTBI induces significant alterations in brain functional connectivity.
  • rmTBI leads to specific protein changes in brain regions not showing apparent morphological damage.
  • These findings provide insights into the molecular mechanisms of rmTBI-induced neurodegeneration.