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J Neurotrauma. 2019 Feb 15;36(4):601-608. doi: 10.1089/neu.2018.5741. Epub 2018 Aug 13.

Alterations of Parenchymal Microstructure, Neuronal Connectivity, and Cerebrovascular Resistance at Adolescence after Mild-to-Moderate Traumatic Brain Injury in Early Development.

Author information

1
1 Department of Radiology and Biomedical Imaging, Yale University School of Medicine , New Haven, Connecticut.
2
2 Department of Pharmacology, Physiology and Neuroscience, Rutgers Biomedical and Health Sciences-New Jersey Medical School , Newark, New Jersey.
3
3 Department of Molecular, Cell and Systems Neuroscience, University of California at Riverside , Riverside, California.
4
4 Department of Biomedical Engineering, Yale University , New Haven, Connecticut.
5
5 Department of Radiology, Rutgers Biomedical and Health Sciences-New Jersey Medical School , Newark, New Jersey.

Abstract

Traumatic brain injury (TBI) is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence.1 Based on the nonlocalized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity, and neurovascular function, are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2 months after injury, using functional MRI (fMRI) and diffusion tensor imaging (DTI). fMRI-based resting-state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus, and thalamus, accompanied by decrease in spatial extent of their corresponding RSFC networks and interhemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus, and motor cortex. DTI measures of fractional anisotropy and apparent diffusion coefficient, reporting on axonal and microstructural integrity of the brain, indicated similar interhemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus, and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in interhemispheric structural connectivity. Hippocampus, thalamus, and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance, and parenchymal microstructure in the adolescent brain, indicating the highly diffuse and persistent nature of the lateral fluid percussion TBI early in development.

KEYWORDS:

adolescence; cerebrovascular; connectivity; fMRI; traumatic brain injury

PMID:
29855211
PMCID:
PMC6354598
[Available on 2020-02-15]
DOI:
10.1089/neu.2018.5741

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