Functional Recovery and Regeneration of Descending Tracts in Rats After Spinal Cord Transection in Infancy

Zeng

et al. 2007

Journal of Neurotrauma

Spinal cord transection results in severe neurological sequelae, and to date, there is no effective treatment. Because of the limited capacity for axonal regeneration in the spinal cord, recovery is minimal. Recently, efforts have been made to establish, by grafting neural tissue, a functional relay-station between the severed stumps of the injured cord. Previously, we used co-transplantation of neural stem cells (NSCs) and Schwann cells (SCs) to improve functional recovery of transected spinal cord. However, this effort has been partially impeded by limited neuronal differentiation of transplanted NSCs. To circumvent this problem, we have pre-differentiated NSCs toward neurons in vitro with the application of retinoic acid (RA) prior to cell grafting. Further, we genetically modified SCs to overexpress human neurotrophin-3 (hNT-3). When these cells were co-transplanted into the transected spinal cord of rats, injured animals had partial improvement (both functionally and structurally), including improved Basso, Beattie, and Bresnahan (BBB) scores, increased axonal regeneration/remyelination, and reduced neuronal loss. However, this pre-differentiation of NSCs in vitro only mildly improved neuronal differentiation of NSCs in vivo.

Section: Preparation Of Cells For Transplantationmentioning

confidence: 99%

Co-Transplantation of Neural Stem Cells and NT-3-Overexpressing Schwann Cells in Transected Spinal Cord

Zeng

et al. 2007

Journal of Neurotrauma

J of Comparative Neurology

“…tal rats with completely transected spinal cords, in some cases implanted with fetal spinal cord, have been reported to make partial functional recovery with evidence of supraspinal innervation of parts of the cord caudal to the lesion (Iwashita et al, 1994;Wakabayashi et al, 2001;Hase et al, 2002). However, none of these studies provided direct evidence that this finding was due to regeneration of injured axons rather than growth of new ones occurring as part of normal development.…”

mentioning

confidence: 99%

Regeneration of supraspinal axons after complete transection of the thoracic spinal cord in neonatal opossums (Monodelphis domestica)

Fry

Stolp

Lane

et al. 2003

These studies define the time table and origin of supraspinal axons regenerating across a complete spinal transection in postnatal Monodelphis domestica. After lumbar (L1) spinal cord injection of fluorophore-dextran amine conjugate on postnatal (P) day 4, a consistent number of neurons could be labeled. The numbers of labeled neurons remained stable for several weeks, but subsequently declined by P60 in control animals and by P35 in animals with complete spinal transection (T4-T6) performed at P7. In control animals, 25-40% of neurons labeled with a fluorophore injected (L1) at P4 could also be double-labeled by a second fluorophore injected (T8-T10) at different older ages. In spinally transected animals, total numbers of neurons labeled with the second marker were initially lower compared with age-matched controls, but were not significantly different by 3 weeks after injury. The proportion of double-labeled neurons in spinally transected animals increased from approximately 2% 1 week after injury (P14) to approximately 50% by P60, indicating that a substantial proportion of neurons with axons transected at P7 is able to regenerate and persist into adulthood. However, the proportion of axons originating from regenerating neurons made only a small contribution at older ages to total numbers of fibers growing through the injury site, because much of development of the spinal cord occurs after P7. Evidence was obtained that degenerating neurons with both apoptotic and necrotic morphologies were present in brainstem nuclei; the number of neurons with necrotic morphology was much greater in the brainstem of animals with spinal cords transected at P7.

“…The anodal (?) electrode was inserted percutaneously into the scalp while the cathodal (-) electrode was placed in the mouth [18]. The intensity of stimulus was about 15 mA and was of 0.2 ms duration.…”

Section: Electrophysiological Evaluationmentioning

confidence: 99%

Artificial collagen-filament scaffold promotes axon regeneration and long tract reconstruction in a rat model of spinal cord transection

et al. 2015

Traumatically injured spinal cord (SC) displays structural damage that includes discontinuity of long tracts and cavitations. Axonal regrowth beyond the lesion is necessary to achieve functional recovery following SC injury. We report here the development of an artificial collagen-filament (CF) scaffold to replace the SC in 8-week-old female Fisher rats. Axonal sprouting and regrowth was very rapid following grafting of the CF. One week after implantation, the scaffold was filled with cells of host origin and with regenerated axons. Histological examination of SC adjacent to the scaffold showed little cavity formation or fibrous scarring. Eight weeks after implantation, myelinated nerve fibers were found in the scaffold and 10-25 % of rubrospinal tracts were repaired. Four to six weeks after transplantation, motor evoked potentials were recorded in CF-grafted rats but were not detectable in non-grafted rats. Electrophysiological and histological examinations revealed the grafted CF was likely to function as a nerve tract. In addition, these results suggest that collagen fibers may provide a permissive microenvironment for the elongation of SC axons and to support the process of spinal cord regeneration.