Traumatic brain injury augurs ill for prolonged deficits in the brain\u2019s structural and functional integrity following controlled cortical impact injury

Abdalla Z Mohamed,Paul Cumming,Fatima A Nasrallah

doi:10.1038/s41598-021-00660-5

Abstract

Previous neuroimaging studies in rodents investigated effects of the controlled cortical impact (CCI) model of traumatic brain injury (TBI) within one-month post-TBI. This study extends this temporal window to monitor the structural–functional alterations from two hours to six months post-injury. Thirty-seven male Sprague–Dawley rats were randomly assigned to TBI and sham groups, which were scanned at two hours, 1, 3, 7, 14, 30, 60 days, and six months following CCI or sham surgery. Structural MRI, diffusion tensor imaging, and resting-state functional magnetic resonance imaging were acquired to assess the dynamic structural, microstructural, and functional connectivity alterations post-TBI. There was a progressive increase in lesion size associated with brain volume loss post-TBI. Furthermore, we observed reduced fractional anisotropy within 24 h and persisted to six months post-TBI, associated with acutely reduced axial diffusivity, and chronic increases in radial diffusivity post-TBI. Moreover, a time-dependent pattern of altered functional connectivity evolved over the six months’ follow-up post-TBI. This study extends the current understanding of the CCI model by confirming the long-term persistence of the altered microstructure and functional connectivity, which may hold a strong translational potential for understanding the long-term sequelae of TBI in humans.

Highlights

Previous neuroimaging studies in rodents investigated effects of the controlled cortical impact (CCI) model of traumatic brain injury (TBI) within one-month post-TBI
The results revealed significant connectivity differences in the TBI group compared to the sham group at day[1], with relatively increased functional connectivity observed at day[1] in the ipsilateral-ipsilateral and ipsilateral-contralateral sensorimotor regions and executive network seeds (FDR corrected, p ≤ 0.05)
By utilising a multi-MRI approach, we highlight a central position of grey matter regions corresponding to the default model network (DMN) in this rather complex and dynamic process, which was associated with deficits in the integrity of critical white matter tracts, mainly the cingulum and corpus collosum

Summary

Introduction

Previous neuroimaging studies in rodents investigated effects of the controlled cortical impact (CCI) model of traumatic brain injury (TBI) within one-month post-TBI. Integrity as reflected by lower fractional anisotropy (FA) and increased diffusivity measures in major white matter tracts in rodent brain up to one month post-TBI2,8 These DTI alterations correlated with the extent of axonal injury within hours post-TBI6,25, and with the degree of neuroinflammation[8,11] and the extent of demyelination up to one month post-TBI2,25. The resting state functional MRI (rsfMRI) technique provides an index of the extent of perturbed connectivity in the rodent CCI model[27,28,29,30] and the fluid-percussion injury models[31,32] Those studies consistently showed decreased functional connectivity ipsilateral to the injury and increased functional connectivity in contralateral brain structures in the motor circuits, sensory cortex, cerebellum, basal ganglia, and thalamus up to one month following TBI4,27–30

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Conclusion