Restorative Neurology and Neuroscience - Volume 2, issue 4-6

Authors: Anderson, Douglas K. | Reier, Paul J. | Wirth III, Edward D. | Theele, Daniel P. | Mareci, Thomas | Brown, Stacy A.

Article Type: Research Article

Abstract: This review summarizes a series of experiments involving transplants of embryonic feline CNS tissue into chronic compression lesions of the adult cat spinal cord. Fetal spinal cord (FSC), caudal brainstem (BSt), neocortex (NCx) or a combination of either FSC/NCx or FSC/BSt was transplanted as solid pieces or as a suspension of dissociated cells into the developed cystic cavities produced by static-load compression trauma 2–10 weeks prior to grafting. All cats were immunosuppressed with cyclosporin A and their locomotor function was assessed for 6–30 weeks. Following the period of evaluation, all recipients were perfused with fixative and tissue specimens, taken at …the transplantation site, were processed for general histological and/or immunocytochemical analysis. Viable graft tissue was found in all animals with the exception of two cats which showed active rejection of their transplants. All of the viable intraspinal grafts were extensively vascularized and did not show any signs of imminent or on-going tissue rejection. Fetal cat CNS grafts showed an extended maturational phase in that features of immature neural tissue (e.g. a paucity of myelination) were still seen even 6–9 weeks after transplantation. By 20–30 weeks, FSC and BSt grafts had attained a more advanced stage of maturation. Transplants in these chronic lesions were extensively blended with both the gray and white matter of the host spinal cord and could be visualized by magnetic resonance imaging (MRI). MRI could also detect regions of cavitation at the graft–host interface, as well as within some transplants. While preliminary evidence from behavioral studies suggest that the FSC and BSt grafts may improve or spare locomotor function in some recipients, a more rigorous analysis of post-grafting locomotor function is required to determine conclusively the functionality of these transplants. Show more

Keywords: Spinal cord transplantation, Fetal spinal cord, Brainstem and neocortical grafts, Compression spinal cord injury

DOI: 10.3233/RNN-1991-245621

Citation: Restorative Neurology and Neuroscience, vol. 2, no. 4-6, pp. 309-325, 1991

Authors: Bregman, Barbara Sypniewski | Bernstein-Goral, Holli | Kunkel-Bagden, Ellen

Article Type: Research Article

Abstract: We are using neural tissue transplantation after spinal cord injury to identify the rules which determine the response of young neurons to injury, to identify the mechanisms underlying anatomical plasticity and recovery of function following spinal cord injury, and to determine the conditions which change during development, leading to the more restricted growth capacity of mature neurons following injury. Spinal cord lesions at birth interrupt different pathways at different relative stages in their development. Neural tissue transplants modify the response of the immature central nervous system neurons to injury. In the current studies, we have used neuroanatomical and behavioral methods …to compare the response of the late-developing corticospinal pathway with that of brainstem–spinal pathways which are intermediate in their development and that of the relatively mature dorsal root pathway. We find that both late-developing and regenerating neuronal populations contribute to the transplant-induced anatomical plasticity, and suggest that this anatomical plasticity underlies the transplant-mediated sparing and recovery of function. Show more

Keywords: Regeneration, Red nucleus, Corticospinal tract, Development, Dorsal root, Neonatal lesion

DOI: 10.3233/RNN-1991-245622

Citation: Restorative Neurology and Neuroscience, vol. 2, no. 4-6, pp. 327-338, 1991

Authors: Goldberger, Michael E.

Article Type: Research Article

Abstract: The mechanisms underlying recovery of function following damage to the CNS, although suspected, are virtually unknown. After damage to the adult cat spinal cord, recovery of motor behavior depends on which systems have been interrupted and which remain intact. For example, following hemisection, overground (voluntary) and reflex locomotion recover and, although a normal kinematic pattern recovers, accurate placement of the limb during locomotion does not return to normal levels. This recovery is associated with lowering of thresholds for postural reflexes suggesting that increased afferent input may compensate for diminished descending control. In contrast, after unilateral loss of afferent input by …lumbosacral deafferentation, (L1 -S2 dorsal roots cut) overground locomotion recovers but a permanently abnormal kinematic pattern is used; reflex locomotion (bipedal locomotion on a treadmill) does not recover at all in the deafferented hindlimb. The specificity of the recovery suggests that increased input from descending pathways, which is required for overground but not reflex locomotion may compensate for loss of afferent input. Anatomical sequellae of these two lesion types have been examined. Studies after hemisection support the notion of a permanently increased dorsal root input as mapped by monoclonal antibody ‘rat 102’. This is associated with a transient increase in GAP-43 labeling in the dorsal horn. In contrast, after deafferentation an increase is found in the descending serotonergic input to the deafferented side. These observations suggest that recovery of specific locomotor behavior can be used to predict compensatory changes in spared pathways. For the study of the effects of transplants, we have used complete spinal transections in newborn kittens with transplantation of E26 cat spinal cord into the transection site. The normal kitten develops overground locomotion beginning the end of the first week postnatal but reflex locomotion is delayed until the end of the second week. After transection on the first day of life, with or without a transplant, reflex locomotion begins precociously. Overground locomotion fails to develop in transection-only animals but does develop in animals with transection and transplant. This locomotion although clearly abnormal, shows postnatal development in terms of weight support and lateral stability. Furthermore, there is some indication of coordination between fore and hind limbs. These observations suggest that the transplants permit the development of some descending control although the anatomical correlates of this sparing/recovery of function are uncertain; the transplant rescues neurons caudal to the transection and also permits regeneration of some descending pathways into the transplant and caudally into host spinal cord. Show more

DOI: 10.3233/RNN-1991-245623

Citation: Restorative Neurology and Neuroscience, vol. 2, no. 4-6, pp. 339-350, 1991