Abstract
BackgroundFunctional recovery after brain injury in animals is improved by marrow stromal cells (MSC) which stimulate neurite reorganization. However, MRI measurement of neurite density changes after injury has not been performed. In this study, we investigate the feasibility of MRI measurement of neurite density in an animal model of traumatic brain injury (TBI) with and without MSC treatment.MethodsFifteen male Wistar rats, were treated with saline (n = 6) or MSCs (n = 9) and were sacrificed at 6 weeks after controlled cortical impact (CCI). Healthy non-CCI rats (n = 5), were also employed. Ex-vivo MRI scans were performed two days after the rats were sacrificed. Multiple-shell hybrid diffusion imaging encoding scheme and spherical harmonic expansion of a two-compartment water diffusion displacement model were used to extract neurite related parameters. Bielshowski and Luxol Fast blue was used for staining axons and myelin, respectively. Modified Morris water maze and neurological severity score (mNSS) test were performed for functional evaluation. The treatment effects, the correlations between neurite densities measured by MRI and histology, and the correlations between MRI and functional variables were calculated by repeated measures analysis of variance, the regression correlation analysis tests, and spearman correlation coefficients.ResultsNeurite densities exhibited a significant correlation (R2>0.80, p<1E−20) between MRI and immuno-histochemistry measurements with 95% lower bound of the intra-correlation coefficient (ICC) as 0.86. The conventional fractional anisotropy (FA) correlated moderately with histological neurite density (R2 = 0.59, P<1E−5) with 95% lower bound of ICC as 0.76. MRI data revealed increased neurite reorganization with MSC treatment compared with saline treatment, confirmed by histological data from the same animals. mNSS were significantly correlated with MRI neurite density in the hippocampus region.ConclusionsThe present studies demonstrated that neurite density can be estimated by MRI after TBI and MRI measurement of neurite density is a sensitive marker to MSC treatment response.
Highlights
Traumatic brain injury (TBI) is a major cause of mortality and disability, especially in children and young adults
We evaluate the effect of a restorative treatment of traumatic brain injury (TBI) using human marrow stromal cells [5,6,26] on neurite density measured by hybrid diffusion imaging (HYDI) MRI [20] with spherical harmonic expansion of a two-compartment water diffusion displacement model [26] and histology after TBI
Significant correlations between MRI and histological neurite density were detected in TBI left (R2 = 0.83, P = 0.006), right, normal left (R2 = 0.87, P = 0.6), normal right (R2 = 0.86, P = 0.06)
Summary
Traumatic brain injury (TBI) is a major cause of mortality and disability, especially in children and young adults. There is no effective neuroprotective treatment to promote functional recovery after TBI [2,3]. Neurorestorative strategies designed to promote brain remodeling and to enhance functional recovery after various central nervous system (CNS) disorders, such as stroke, intracerebral hemorrhage, spinal cord injury, multiple sclerosis, and TBI, using pharmacological and cell based neurorestorative techniques have shown promising results in animals [4]. Treating brain injury with marrow stromal cells (MSCs) after stroke promotes axonal remodeling and increases oligodendrocyte formation [5,6]. Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC) which stimulate neurite reorganization. We investigate the feasibility of MRI measurement of neurite density in an animal model of traumatic brain injury (TBI) with and without MSC treatment
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
