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

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.

Identification of Severities of Spinal Cord Injury during Acute Phase in Rats by Diffusion Tensor Imaging

“…However, AD showed significant changes between day 3 and day 7. This characteristics may be due to the detectable axonal collapse at early time points of acute SCI, which was consistent with previous research results [33,34]. The RD values of the lesion epicenter in severe group remained highest, but did not change with times and severities.…”

Improving Diagnostic Workup Following Traumatic Spinal Cord Injury: Advances in Biomarkers

“…DTI assesses the microstructural integrity of fiber tracts and, thus, has higher sensitivity to early structural changes [ 28 , 45 ]. Measuring spared white matter by means of non-invasive DTI as well as in post-mortem histological samples showed a strong correlation between both measures, pointing at the usefulness of DTI for assessing neuronal tract integrity non-invasively [ 46 ]. In both preclinical animal models of SCI and human SCI patients, differences in DTI parameters between SCI and healthy control groups were detected.…”

Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats

“…In general, the one-time intraperitoneal application of the stable gastric pentadecapeptide BPC 157 is much like the engraftment of neural stem cells [16] or bone marrow stromal cells [17] into the lesion site. One should consider the primary phase lesion and hemorrhaging that results from mechanical damage during SCI as well as the secondary phase lesion that lasts several hours or even several months and is accompanied by edema, hemorrhage, inflammation, and cytotoxic edema [44][45][46][47] and may extend to the white matter area and lead to white matter degeneration and damage [48,49]. This substantiates the evidence that the spared white matter holds the key to the functional motor recovery of the hind limbs after SCI and is closely correlated with the functional restoration of the paralyzed hind limbs [50][51][52].…”

“…+ P < 0.05 saline and BPC 157 groups vs. laminectomy animals sprouting of axons in the corticospinal tract [56][57][58] and the formation of neural circuits by spared spinal cord tissue [26]; these processes lead to partial functional recovery [59] or the formation of the neural fiber connection between the central pattern generator (CPG) and interneurons in the spinal cord, which can enable rhythmic movement [60][61][62]. Thus, to illustrate these combining points (i.e., [13,44,63]), considering that white matter injury is the major cause of functional loss after SCI [45,52], it is important to note that cysts and the loss of axons instead of hemorrhagic areas were observed in the white matter in all of the controls beginning on day 7 and that the rats exhibited a tail motor score that persisted with only small improvements, sustained debilitation, sustained tail spasticity until the end of the experiment (day 360), a decrease in the number of large myelinated axons in the caudal nerve, a higher MUP (giant potential) in the tail muscle, and a group of atrophic fibers that likely represented a large unit that acquired many fibers through collateral reinnervation and then degenerated. Autotomy that occurs long after injury may appear as pain that occurs below the level of the injury (belowlevel pain) [64,65], and the late spontaneous worsening may be the result of complete deafferentation of one or several spinal segments the stimulation of the nerve plexus, or dorsal root injury [66].…”

“…Likewise, BPC 157 ameliorates healing and recovers the impaired function of severely injured muscles that otherwise fail to spontaneously heal and plays a role after complete transection, crush, and denervation injuries [77][78][79][80] and after succinylcholine intramuscular application, muscle lesion, neuromuscular junction failure, fasciculations, paralysis, and hyperalgesia [81]. Likewise, given that the gray matter is particularly vulnerable during the primary phase [44,63], we should note that, from day 7, the controls presented with edema and the loss of motoneurons in the gray matter, disturbances that were largely counteracted in BPC 157-treated rats (Table 2 and Fig. 4).…”