Abstract

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.

Highlights

  • Spinal cord injury (SCI) may cause partial or total sensory and motor dysfunction beneath the injury interface, as well as the loss of autonomic nerve function [1, 2]

  • luxol fast blue (LFB) stained myelin sheaths were evenly distributed throughout the white matter of the control rat spinal cord, and gray matter appeared in a typical H-shape and contained a large amount of purple neuronal Nissl bodies (Figure 2(a))

  • At 1 day after SCI, a circular-like hypointensity signal was observed in the spinal cord close to the dorsal column (DC) region in the T2 image at the lesion core (LC), indicating acute hemorrhage and a blurred boundary between white matter and gray matter

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Summary

Introduction

Spinal cord injury (SCI) may cause partial or total sensory and motor dysfunction beneath the injury interface, as well as the loss of autonomic nerve function [1, 2]. Most primary phase lesions come from mechanical damage and directly result from the SCI and hemorrhage, and the gray matter is vulnerable during this phase [3]. Experimental data have demonstrated that spared white matter of less than 5% resulted in a loss of weight-supporting ability in the rat hindlimbs; spared white matter of 12%-15% at the lesion center might maintain high-quality hind limb movements, such as consistent bilateral, hindlimb, weightsupported plantar steps, while consistent forelimb-hindlimb coordination and precise stepping (horizontal bar and beam walking) required contact between multiple fiber tracts [11, 13, 14]. Because white matter injury is the major cause of function loss after SCI [4, 12], many therapeutic strategies focus on the effects of secondary lesions to white matter

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