Diffusion tensor imaging of spinal cord parenchyma lesion in rat with chronic spinal cord injury

et al. 2020

Cell Transplant

MicroRNAs (miRNAs) function as gene expression switches, and participate in diverse pathophysiological processes of spinal cord injury (SCI). Olfactory ensheathing cells (OECs) can alleviate pathological injury and facilitate functional recovery after SCI. However, the mechanisms by which OECs restore function are not well understood. This study aims to determine whether silencing miR-199a-5p would enhance the beneficial effects of the OECs. In this study, we measured miR-199a-5p levels in rat spinal cords with and without injury, with and without OEC transplants. Then, we transfected OECs with the sh-miR-199a-5p lentiviral vector to reduce miR-199a-5p expression and determined the effects of these OECs in SCI rats by Basso–Beattie–Bresnahan (BBB) locomotor scores, diffusion tensor imaging (DTI), and histological methods. We used western blotting to measure protein levels of Slit1, Robo2, and srGAP2. Finally, we used the dual-luciferase reporter assay to assess the relationship between miR-199-5p and Slit1, Robo2, and srGAP2 expression. We found that SCI significantly increased miR-199a-5p levels ( P < 0.05), and OEC transplants significantly reduced miR-199a-5p expression ( P < 0.05). Knockdown of miR-199a-5p in OECs had a better therapeutic effect on SCI rats, indicated by higher BBB scores and fractional anisotropy values on DTI, as well as histological findings. Reducing miR-199a-5p levels in transplanted OECs markedly increased spinal cord protein levels of Slit1, Robo2, and srGAP2. Our results demonstrated that transplantation of sh-miR-199a-5p-modified OECs promoted functional recovery in SCI rats, suggesting that miR-199a-5p knockdown was more beneficial to the therapeutic effects of OEC transplants. These findings provided new insights into miRNAs-mediated therapeutic mechanisms of OECs, which helps us to develop therapeutic strategies based on miRNAs and optimize cell therapy for SCI.

Section: Discussionsupporting

confidence: 91%

Transplantation of sh-miR-199a-5p-Modified Olfactory Ensheathing Cells Promotes the Functional Recovery in Rats with Contusive Spinal Cord Injury

Gao

et al. 2020

Cell Transplant

“…As previously reported, fraction anisotropy (FA) and AD are closely correlated with axonal integrity [ 16 , 19 , 20 ], and RD reflects myelination integrity [ 16 ]. Meanwhile, the mean diffusivity (MD) could provide information about the state of edema in SCI and was sensitive to cysts in chronic SCI [ 21 , 22 ]. Collectively, using DTI to test these parameters in the white matter enables the assessment of microstructural information in the white matter tissue [ 4 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Testing Pathological Variation of White Matter Tract in Adult Rats after Severe Spinal Cord Injury with MRI

Song

BioMed Research International

et al. 2018

Self Cite

The purpose of this study was to assess the pathological variation in white matter tracts in the adult severe thoracic contusion spinal cord injury (SCI) rat models combined with in vivo magnetic resonance imaging (MRI), as well as the effect of spared white matter (WM) quantity on hindlimb motor function recovery. 7.0T MRI was conducted for all experimental animals before SCI and 1, 3, 7, and 14 days after SCI. The variation in the white matter tract in different regions of the spinal cord after SCI was examined by luxol fast blue (LFB) staining, NF200 immunochemistry, and diffusion tensor imaging (DTI) parameters, including fraction anisotropy, mean diffusivity, axial diffusion, and radial diffusivity. Meanwhile, Basso-Beattie-Bresnahan (BBB) open-field scoring was performed to evaluate the behavior of the paraplegic hind limbs. The quantitative analysis showed that spared white matter measures assessed by LFB and MRI had a close correlation (R2 = 0.8508). The percentage of spared white matter area was closely correlated with BBB score (R2 = 0.8460). After SCI, spared white matter in the spinal cord, especially the ventral column WM, played a critical role in motor function restoration. The results suggest that the first three days provides a key time window for SCI protection and treatment; spared white matter, especially in the ventral column, plays a key role in motor function recovery in rats. Additionally, DTI may be an important noninvasive technique to diagnose acute SCI degree as well as a tool to evaluate functional prognosis. During the transition from nerve protection toward clinical treatment after SCI, in vivo DTI may serve as an emerging noninvasive technique to diagnose acute SCI degree and predict the degree of spontaneous functional recovery after SCI.

“…Previous studies have proposed many correction methods for EPI data based on registration method 21,24,30 and robust tensor fitting technique, 23,28,42 but these methods are mainly specific to the brain. Here, we proposed an image correction strategy to reduce the Notably, many high-resolution spinal cord in vivo DTI studies are usually performed at 7T or higher magnetic field and using rodents 43,44 or small-sized NHP animal (marmoset) 12,13 as models. Increased magnetic field and minimized aperture allow for high-quality images, which contributes to the accurate analysis of SCI status and alterations generated by therapeutic interventions.…”

Section: Discussionsmentioning

confidence: 99%

Image correction for diffusion tensor imaging of Rhesus monkey thoracic spinal cord

Rao

Liu

J of Medical Primatology

et al. 2019

Self Cite

Background: The relatively tiny spinal cord of non-human primate (NHP) causes increased challenge in diffusion tensor imaging (DTI) post-processing. This study aimed to establish a reliable correction strategy applied to clinical DTI images of NHP. Methods: Six normal and partial spinal cord injury (SCI) rhesus monkeys underwent 3T MR scanning. A correction strategy combining multiple iterations and non-rigid deformation was used for DTI image post-processing. Quantitative evaluations were then conducted to investigate effects of distortion correction.Results: After correction, longitudinal geometric distortion, global distortion, and residual distance errors were all significantly decreased (P < 0.05). Fractional anisotropy at the injured site was remarkably lower than that at the contralateral site (P = 0.0488) and was substantially lower than those at the adjacent superior (P = 0.0157) and inferior (P = 0.0128) areas at the same side. Conclusions:Our image correction strategy can improve the quality of the DTI images of NHP thoracic cords, contributing to the development of SCI preclinical research. K E Y W O R D S image correction strategy, non-human primates, preclinical research, spinal cord injury | 321 RAO et Al.