Fetal Neural Grafts and Repair of the Injured Spinal Cord
Corresponding Author
Douglas K. Anderson
Department of Neuroscience
Department of Neurological Surgery University of Florida College of Medicine, JHMHC, Gainesville, Florida, USA
Depatment of Neuroscience, University of Florida Brain Institute, Gainesville, Florida, USA
Gainesville Veterans Affairs Medical Center, Gainesville, Florida, USA
Corresponding author: Dr. Douglas K. Anderson, Department of Neuroscience, P.O. Box 100244, University of Florida College of Medicine, JHMHC, Gainesville, Florida 32610–0244, USA Tel. +1 (904) 392–6641; Fax +1 (904) 846–0250Search for more papers by this authorDena R. Howland
Department of Neuroscience
Depatment of Neuroscience, University of Florida Brain Institute, Gainesville, Florida, USA
Search for more papers by this authorPaul J. Reier
Department of Neuroscience
Department of Neurological Surgery University of Florida College of Medicine, JHMHC, Gainesville, Florida, USA
Depatment of Neuroscience, University of Florida Brain Institute, Gainesville, Florida, USA
Search for more papers by this authorCorresponding Author
Douglas K. Anderson
Department of Neuroscience
Department of Neurological Surgery University of Florida College of Medicine, JHMHC, Gainesville, Florida, USA
Depatment of Neuroscience, University of Florida Brain Institute, Gainesville, Florida, USA
Gainesville Veterans Affairs Medical Center, Gainesville, Florida, USA
Corresponding author: Dr. Douglas K. Anderson, Department of Neuroscience, P.O. Box 100244, University of Florida College of Medicine, JHMHC, Gainesville, Florida 32610–0244, USA Tel. +1 (904) 392–6641; Fax +1 (904) 846–0250Search for more papers by this authorDena R. Howland
Department of Neuroscience
Depatment of Neuroscience, University of Florida Brain Institute, Gainesville, Florida, USA
Search for more papers by this authorPaul J. Reier
Department of Neuroscience
Department of Neurological Surgery University of Florida College of Medicine, JHMHC, Gainesville, Florida, USA
Depatment of Neuroscience, University of Florida Brain Institute, Gainesville, Florida, USA
Search for more papers by this authorAbstract
Solid or suspension grafts of fetal spinal cord (FSC), caudal brainstem (FBSt), neocortex (FNCx) or a combination of either FSC/FNCx or FSC/FBSt were placed into cavities produced by static loading (i.e., compression) of the spinal cord of adult cats two to 30 weeks after injury. Extensively vascularized, viable graft tissue was found in all animals with the exception of two cats which showed active rejection of their transplants. Surviving grafts showed many immature characteristics 6–9 weeks after transplantation. However, by 20–30 weeks FSC and FBSt grafts were more mature. Grafts integrated with the host gray and white matter and neuritic processes from both host and graft were seen crossing the host-graft interface. Host calcitonin gene related peptide (CGRP)-like immunoreactive axons could be traced into FSC and FBSt grafts. A more restricted ingrowth of host serotonin (5-HT)-like immunoreactive fibers was seen in FSC grafts. Our results suggest that the capacity of homotypic transplants to promote recovery of function is greater than heterotypic transplants. Additionally, it appears that the functional capacity of the graft depends upon graft survival, the time interval between injury and transplantation, and whether or not the lesion cavity was debrided prior to grafting.
References
- 1 Aguayo A, David S, Richardson P, Bray G (1982) Axonal elongation in peripheral and central nervous system transplants. Advances in Cellular Neurobiology 3: 215–234.
- 2 Anderson DK (1991) Antioxidant therapy in experimental spinal cord injury. Restor Neurol Neurosci 2: 169–172.
- 3 Anderson DK, Braughler JM, Hall ED, Waters TR, McCall JM, Means ED (1988) Effects of treatment with U-74006F on neurological outcome following experimental spinal cord compression injury. J Neurosurg 69: 562–567.
- 4 Anderson DK, Howland DR, Reier PJ (1995) Characteristics of intraspinal grafts and locomotor function after spinal cord injury. In: Neural Cell Specification: Molecular Mechanisms and Neurotherapeutic Implication Proceedings of the Third Altschul Symposium, B Juurlink, W Kulyk, P Krone, V Verge, R. Doucette (eds.)Plenum Press: New York .
- 5 Anderson DK, Means ED, Waters TR, Spears CJ (1980) Spinal cord energy metabolism following compression trauma to the feline spinal cord. J Neurosurg 53: 375–380.
- 6 Anderson DK, Prockop LD, Means ED, Hartley LE (1976) Cerebrospinal fluid lactate and electrolyte levels following experimental spinal cord injury. J Neurosurg 44: 715–722.
- 7 Anderson DK, Reier PJ, Wirth ED, III., Theele DP, Brown SA (1991) Delayed grafting of fetal CNS tissue into chronic compression lesions of the adult spinal cord. Restor Neurol Neurosci 2: 309–325.
- 8 Anderson DK, Saunders RD, Demediuk P, Dugan LL, Braughler JM, Hall ED, Means ED, Horrocks LA (1985) Lipid hydrolysis and peroxidation in injured spinal cord. Partial protection with methylprednisolone and vitamin E. CNS Trauma 2: 257–267.
- 9 Anderson DK, Thomas CE (1994) Mechanisms and role of oxygen free radicals in CNS pathology. In: Recent Advances in the Treatment of Neurodegenerative Disorders and Cognitive Dysfunction Proceedings of the International Academy for Biomedical and Drug Research CINP President's Workshop, SZ Langer, J Mendlewicz, G Racagni (eds.), pp 119–124, S Karger A.G.: Basal .
- 10 Anderson DK, Waters TR, Means ED (1988) Pretreatment with alpha tocopherol enhances neurological recovery after experimental spinal cord compression injury. J Neurotrauma 5: 61–68.
- 11 Barres BA, Loroshetz WJ, Chun LL, Corey DP (1990) Ion channel expression by white matter glia-the type -1 astrocyte. Neuron 5: 527–544.
- 12
Beattie MS,
Stokes BT,
Bresnahan JC (1988) Experimental spinal cord injury. Strategies for acute and chronic intervention based on anatomic, physiological, and behavioral studies. In: Pharmacological Approaches to the Treatment of Brain and Spinal Cord Injury, DG Stein,
BA. Sabel (eds.), pp 43–47, Plenum Press:
New York
.
10.1007/978-1-4613-0927-7_3 Google Scholar
- 13 Berkowitz M, Harvey C, Greene CG, Wilson SE (1992) The Economic Consequences of Traumatic Spinal Cord Injury, Demos Publications: New York .
- 14 Bernstein-Goral H, Bregman BS (1993) Spinal cord transplants support the regeneration of axotomized neurons after spinal cord lesions at birth: A quantitative double labelling study. Exp Neurol 23: 118–132.
- 15 Bernstein JJ, Goldberg WJ (1987) Fetal spinal cord homografts ameliorate the severity of lesion-induced hindlimb behavioral deficits. Exp Neurol 98: 633–644.
- 16 Bracken MB, Shepard MJ, Collins WF, Jr., et al (1990) A randomized controlled trial of methylprednisolone or naloxone in the treatment of acute spinal cord injury. NEJM 322: 1405–1411.
- 17 Bracken MB, Shepard MJ, Collins WF, Jr., et al (1992) Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. J Neurosurg 76: 23–31.
- 18 Bregman BS (1987) Spinal cord transplants permit growth of serotonergic axons across the site of neonatal spinal cord transections. Dev Brain Res 34: 265–279.
- 19 Bregman BS, Kunkel-Bagden E (1988) Effect of target and nontarget transplants on neuronal survival and axonal elongation after injury to the developing spinal cord. Prog Brain Res 78: 205–212.
- 20 Bregman BS, Kunkel-Bagden E, Reier PJ, Dai HN, McAtee M, Gao D (1993) Recovery of function after spinal cord injury: Mechanisms underlying transplant-mediated recovery of function differ after spinal cord injury in newborn and adult rats. Exp Neurol 123: 3–16.
- 21 Blight AR (1983) Axonal physiology of chronic spinal cord injury in the cat: Intracellular recording in vitro. Neuroscience 10: 1471–1486.
- 22 Blight AR (1983) Cellular morphology of chronic spinal cord injury in the cat: Analysis of myelinated axons by line-sampling. Neuroscience 10: 521–543.
- 23 Blight AR (1989) Effect of 4-aminopyridine on axonal conduction-block in chronic spinal cord injury. Brain Res Bull 22: 47–52.
- 24 Blight AR, Toombs JP, Bauer MS, Bauer JR Widmer WR (1991) The effects of 4-aminopyridine on neurological deficits in chronic cases of traumatic spinal cord injury in dogs: A phase I clinical trial. J Neurotrauma 8: 103–118.
- 25 David S, Aguayo A (1981) Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rat. Science 214: 931–933.
- 26 Geisler FH, Dorsey FC, Coleman WP (1991) Recovery of motor function following spinal cord injury - A randomized, placebo-controlled trial with GM-1 ganglioside. NEJM 324: 1829–1838.
- 27 Hall ED, Yonkers PA, Andrus PK, Cox JW, Anderson DK (1992) Biochemistry and pharmacology of lipid antioxidants in acute brain and spinal cord injury. J Neurotrauma 9 (Suppl 2): S425–S442.
- 28 Hansebout RR, Blight AR, Fawcett S, Reddy K (1993) Aminopyridine in chronic spinal cord injury: A controlled, double-blind, crossover study in eight patients. J Neurotrauma 10: 1–18.
- 29 Howland DR, Bregman BS, Tessler A, Goldberger M (1995) Transplants enhance locomotion in neonatal kittens whose spinal cords are transected: A behavioral and anatomical study. Exp Neurol (in Press).
- 30 Howland DR, Reier PJ, Anderson DK (1995) Intraspinal transplantation of fetal tissue: Therapeutic potential for spinal cord repair. In: Neurotrauma A Comprehensive Textbook on Head and Spinal Injury, RK Narayan, JE Wilberger, JT Povlishock (eds.), McGraw-Hill, Inc: New York (in press).
- 31 Itoh Y, Tessler A (1990) Regeneration of adult dorsal root axons into transplants of fetal spinal cord and brain - a comparison of growth and synapse formation in appropriate and inappropriate targets. J Comp Neurol 302: 272–293.
- 32 Jakeman LB, Reier PJ (1991) Axonal projections between fetal spinal cord transplants and the adult rat spinal cord: A neuroanatomical tracing study of local interactions. J Comp Neurol 307: 311–334.
- 33 Kakulas BA (1987) The clinical neuropathology of spinal cord injury. A guide to the future. Paraplegia 25: 212–216.
- 34 Kliot M, Smith GM, Siegal JD, Silver J (1990) Astrocyte-polymer implants promote regeneration of dorsal root fibers into the adult mammalian spinal cord. Exp Neurol 109: 57–69.
- 35 Kunkel-Bagden E, Bregman BS (1990) Spinal cord transplants enhance the recovery of locomotor function after spinal cord injury at birth. Exp Brain Res 81: 25–34.
- 36 Kunkel-Bagden E, Schnell L, Dai HN, Gao D, Schwab ME, Bregman BS (1993) Does the regrowth of injured corticospinal fibers elicited by antibodies to neurite growth inhibitors lead to recovery of motor function Soc Neurosci Absts 23: 681.
- 37 Li Y, Raisman G (1994) Schwann cells induce sprouting in motor and sensory axons in the adult rat spinal cord. J Neurosci 14: 4050–4063.
- 38 Means ED, Anderson DK, Waters TR, Kalaf L (1981) Effect of methylprednisolone in compression trauma to the feline spinal cord. J Neurosurg 55: 200–208.
- 39
Nornes H,
Bjorklund A,
Stenevi U (1984) Transplantation strategies in spinal cord regeneration. In: Neural Transplants - Development and Function, JR Sladek,
DM. Gash (eds.), pp. 407–421, Plenum Press:
New York
.
10.1007/978-1-4684-4685-2_17 Google Scholar
- 40 Privat A, Mansour H, Rajaofetra N, Geffard M (1989) Intraspinal transplants of serotonergic neurons in the adult rat. Brain Res Bull 22: 123–129.
- 41 Reier PJ (1985) Neural tissue grafts and repair of the injured spinal cord. Neuropath Appl Neurobiol 11: 81–104.
- 42 Reier PJ, Anderson DK, Thompson FJ, Stokes BT (1992) Neural tissue transplantation and CNS trauma: Anatomical and functional repair of the injured spinal cord. J Neurotrauma 9 (Suppl 1 S223–S248.
- 43 Reier PJ, Anderson DK, Schrimsher GW, Bao J, Friedman RM, Ritz LA, Stokes BT (1994) Neural cell grafting: Anatomical and functional repair of the spinal cord. In: The Neurobiology of Central Nervous System Trauma. S Salzman, Al. Faden (eds.), pp 288–311, Oxford University Press: New York , Oxford .
- 44 Reier PJ, Bregman BS, Wujek JR (1986) Intraspinal transplantation of embryonic spinal cord tissue in neonatal and adult rats. J Comp Neurol 247: 275–296.
- 45 Reier PJ, Stokes BT, Thompson FJ, Anderson DK (1992) Fetal cell grafts into resection and contusion/compression injuries of the rat and cat spinal cord. Exp Neurol 115: 177–188.
- 46 Richardson PM, McGuinness UM, Aguayo AJ (1980) Axons from CNS neurones regenerate into PNS grafts. Nature 284: 264–265.
- 47 Rosenbluth J, Hasegawa M, Shirasaki N, Rosen CL, Liu Z (1990) Myelin formation following transplantation of normal fetal glia into myelin-deficient rat spinal cord. J Neurocytol 19: 718–730.
- 48 Schnell L, Schwab ME (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 343: 269–272.
- 49 Schwab ME, Schnell L (1991) Channeling of developing rat corticospinal tract axons by myelin-associated neurite growth inhibitors. J Neurosci 11: 709–721.
- 50 Singh RVP, Suys S, Villanueva PA (1995) Prevention and treatment of medical complications. In: Contemporary Management of Spinal Cord Injury, ED Benzel, CH Tator (eds.), pp 195–215 American Association of Neurological Surgeons: Park Ridge .
- 51 Stokes BT, Reier PJ (1991) Oxygen transport in intraspinal fetal grafts: Graft-host relations. Exp Neurol 111: 312–323.
- 52 Stokes BT, Reier PJ (1992) Fetal grafts alter chronic behavioral outcome after contusion damage to the adult rat spinal cord. Exp Neurol 116: 1–12.
- 53 Tator CA (1995) Epidemiology and general characteristics of the spinal cord injured patient. In: Contemporary Management of Spinal Cord Injury, ED Benzel, CH Tator (eds.), pp 9–13, American Association of Neurological Surgeons: Park Ridge .
- 54 Tessler A, Himes BT, Houle J, Reier PJ (1988) Regeneration of adult dorsal root axons into transplants of embryonic spinal cord. J Comp Neurol 270: 537–548.
- 55 Waxman SG (1992) Demyelination in spinal cord injury and multiple sclerosis: What can we do to enhance functional recovery J Neurotrauma 9 (Suppl 1): S105–S117.
- 56 Wirth III ED, Theele DP, Mareci TH, Anderson DK, Brown SA, Reier PJ (1992) In vivo magnetic resonance imaging of fetal cat neural tissue transplants in the adult cat spinal cord. J Neurosurg 76: 261–274.
- 57 Xu XM, Guenard V, Kleitman N, Bunge MB (1995) Axonal regeneration into Schwann cell-seeded guidance channels grafted into transected adult rat spinal cord. J Comp Neurol 351: 145–160.
- 58 Yakovleff A, Roby-Brami A, Guezard B, Mansour H, Bussel B, Privat A (1989) Locomotion in rats transplanted with noradrenergic neurons. Brain Res Bull 22: 115–121.