 |
 Previous Article | Next Article 
The Journal of Neuroscience, May 15, 1998, 18(10):3803-3815
Long-Distance Axonal Regeneration in the Transected Adult Rat
Spinal Cord Is Promoted by Olfactory Ensheathing Glia Transplants
Almudena
Ramón-Cueto1, 2,
Giles W.
Plant1,
Jesus
Avila2, and
Mary Bartlett
Bunge1, 3
1 The Chambers Family Electron Microscopy Laboratory,
The Miami Project to Cure Paralysis, and 3 Departments of
Cell Biology and Anatomy and Neurological Surgery, University of Miami
School of Medicine, Miami, Florida 33101, and 2 Centro de
Biología Molecular "Severo Ochoa" (Consejo Superior de
Investigaciones Cientificas), Facultad de Ciencias, Universidad
Autónoma de Madrid, Cantoblanco 28049 Madrid, Spain
The lack of axonal regeneration in the injured adult mammalian
spinal cord leads to permanent functional impairment. To induce axonal
regeneration in the transected adult rat spinal cord, we have used the
axonal growth-promoting properties of adult olfactory bulb ensheathing
glia (EG). Schwann cell (SC)-filled guidance channels were grafted to
bridge both cord stumps, and suspensions of pure (98%) Hoechst-labeled
EG were stereotaxically injected into the midline of both stumps, 1 mm
from the edges of the channel. In EG-transplanted animals, numerous
neurofilament-, GAP-43-, anti-calcitonin gene-related peptide (CGRP)-,
and serotonin-immunoreactive fibers traversed the glial scars formed at
both cord-graft interfaces. Supraspinal serotonergic axons crossed the
transection gap through connective tissue bridges formed on the
exterior of the channels, avoiding the channel interior. Strikingly,
after crossing the distal glial scar, these fibers elongated in white
and periaqueductal gray matter, reaching the farthest distance analyzed
(1.5 cm). Tracer-labeled axons present in SC grafts were found to
extend across the distal interface and up to 800 µm beyond in the
distal cord. Long-distance regeneration (at least 2.5 cm) of injured ascending propriospinal axons was observed in the rostral spinal cord.
Transplanted EG migrated longitudinally and laterally from the
injection sites, reaching the farthest distance analyzed (1.5 cm). They
moved through white matter tracts, gray matter, and glial scars,
overcoming the inhibitory nature of the CNS environment, and invaded SC
and connective tissue bridges and the dorsal and ventral roots adjacent
to the transection site. Transplanted EG and regenerating axons were
found in the same locations. Because EG seem to provide injured spinal
axons with appropriate factors for long-distance elongation, these
cells offer new possibilities for treatment of CNS conditions that
require axonal regeneration.
Key words:
axonal regeneration; olfactory ensheathing glia; spinal
cord injury; transplantation; immunohistochemistry; WGA-HRP
Copyright © 1998 Society for Neuroscience 0270-6474/98/18103803-13$05.00/0
This article has been cited by other articles:
|
|
|
|
 
P. Negredo, J.-L. L. Rivero, B. Gonzalez, A. Ramon-Cueto, and R. Manso
Slow- and fast-twitch rat hind limb skeletal muscle phenotypes 8 months after spinal cord transection and olfactory ensheathing glia transplantation
J. Physiol.,
May 15, 2008;
586(10):
2593 - 2610.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Kubasak, D. L. Jindrich, H. Zhong, A. Takeoka, K. C. McFarland, C. Munoz-Quiles, R. R. Roy, V. R. Edgerton, A. Ramon-Cueto, and P. E. Phelps
OEG implantation and step training enhance hindlimb-stepping ability in adult spinal transected rats
Brain,
January 1, 2008;
131(1):
264 - 276.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. FitzGerald and J. Fawcett
Repair in the central nervous system
J Bone Joint Surg Br,
November 1, 2007;
89-B(11):
1413 - 1420.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Santos-Silva, R. Fairless, M. C. Frame, P. Montague, G. M. Smith, A. Toft, J. S. Riddell, and S. C. Barnett
FGF/Heparin Differentially Regulates Schwann Cell and Olfactory Ensheathing Cell Interactions with Astrocytes: A Role in Astrocytosis
J. Neurosci.,
July 4, 2007;
27(27):
7154 - 7167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Au, M. W. Richter, A. J. Vincent, W. Tetzlaff, R. Aebersold, E. H. Sage, and A. J. Roskams
SPARC from Olfactory Ensheathing Cells Stimulates Schwann Cells to Promote Neurite Outgrowth and Enhances Spinal Cord Repair
J. Neurosci.,
July 4, 2007;
27(27):
7208 - 7221.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Su, L. Cao, Y. Zhu, X. Liu, Z. Huang, A. Huang, and C. He
Nogo enhances the adhesion of olfactory ensheathing cells and inhibits their migration
J. Cell Sci.,
June 1, 2007;
120(11):
1877 - 1887.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yakovenko, J. Kowalczewski, and A. Prochazka
Intraspinal Stimulation Caudal to Spinal Cord Transections in Rats. Testing the Propriospinal Hypothesis
J Neurophysiol,
March 1, 2007;
97(3):
2570 - 2574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Rasouli, N. Bhatia, S. Suryadevara, K. Cahill, and R. Gupta
Transplantation of Preconditioned Schwann Cells in Peripheral Nerve Grafts After Contusion in the Adult Spinal Cord. Improvement of Recovery in a Rat Model
J. Bone Joint Surg. Am.,
November 1, 2006;
88(11):
2400 - 2410.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Lu, H. Yang, M. Culbertson, L. Graham, A. J. Roskams, and M. H. Tuszynski
Olfactory Ensheathing Cells Do Not Exhibit Unique Migratory or Axonal Growth-Promoting Properties after Spinal Cord Injury
J. Neurosci.,
October 25, 2006;
26(43):
11120 - 11130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Houle, V. J. Tom, D. Mayes, G. Wagoner, N. Phillips, and J. Silver
Combining an autologous peripheral nervous system "bridge" and matrix modification by chondroitinase allows robust, functional regeneration beyond a hemisection lesion of the adult rat spinal cord.
J. Neurosci.,
July 12, 2006;
26(28):
7405 - 7415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Sasaki, J. A. Black, K. L. Lankford, H. A. Tokuno, S. G. Waxman, and J. D. Kocsis
Molecular Reconstruction of Nodes of Ranvier after Remyelination by Transplanted Olfactory Ensheathing Cells in the Demyelinated Spinal Cord
J. Neurosci.,
February 8, 2006;
26(6):
1803 - 1812.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J- M Nothias, T. Mitsui, J. S. Shumsky, I. Fischer, M. D. Antonacci, and M. Murray
Combined Effects of Neurotrophin Secreting Transplants, Exercise, and Serotonergic Drug Challenge Improve Function in Spinal Rats
Neurorehabil Neural Repair,
December 1, 2005;
19(4):
296 - 312.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. Johansson, I-H. Lee, L. Olson, and C. Spenger
Olfactory ensheathing glial co-grafts improve functional recovery in rats with 6-OHDA lesions
Brain,
December 1, 2005;
128(12):
2961 - 2976.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Richter, P. A. Fletcher, J. Liu, W. Tetzlaff, and A. J. Roskams
Lamina Propria and Olfactory Bulb Ensheathing Cells Exhibit Differential Integration and Migration and Promote Differential Axon Sprouting in the Lesioned Spinal Cord
J. Neurosci.,
November 16, 2005;
25(46):
10700 - 10711.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Boyd, R. Doucette, and M. D. Kawaja
Defining the role of olfactory ensheathing cells in facilitating axon remyelination following damage to the spinal cord
FASEB J,
May 1, 2005;
19(7):
694 - 703.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Ruitenberg, D. B. Levison, S. V. Lee, J. Verhaagen, A. R. Harvey, and G. W. Plant
NT-3 expression from engineered olfactory ensheathing glia promotes spinal sparing and regeneration
Brain,
April 1, 2005;
128(4):
839 - 853.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Fouad, L. Schnell, M. B. Bunge, M. E. Schwab, T. Liebscher, and D. D. Pearse
Combining Schwann Cell Bridges and Olfactory-Ensheathing Glia Grafts with Chondroitinase Promotes Locomotor Recovery after Complete Transection of the Spinal Cord
J. Neurosci.,
February 2, 2005;
25(5):
1169 - 1178.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Sasaki, K. L. Lankford, M. Zemedkun, and J. D. Kocsis
Identified Olfactory Ensheathing Cells Transplanted into the Transected Dorsal Funiculus Bridge the Lesion and Form Myelin
J. Neurosci.,
September 29, 2004;
24(39):
8485 - 8493.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Cao, L. Liu, Z.-Y. Chen, L.-M. Wang, J.-L. Ye, H.-Y. Qiu, C.-L. Lu, and C. He
Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair
Brain,
March 1, 2004;
127(3):
535 - 549.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Boyd, J. Lee, V. Skihar, R. Doucette, and M. D. Kawaja
LacZ-expressing olfactory ensheathing cells do not associate with myelinated axons after implantation into the compressed spinal cord
PNAS,
February 17, 2004;
101(7):
2162 - 2166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Keyvan-Fouladi, G. Raisman, and Y. Li
Functional Repair of the Corticospinal Tract by Delayed Transplantation of Olfactory Ensheathing Cells in Adult Rats
J. Neurosci.,
October 15, 2003;
23(28):
9428 - 9434.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. Hegg, E. Au, A. J. Roskams, and M. T. Lucero
PACAP Is Present in the Olfactory System and Evokes Calcium Transients in Olfactory Receptor Neurons
J Neurophysiol,
October 1, 2003;
90(4):
2711 - 2719.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Li, Y. Sauve, D. Li, R. D. Lund, and G. Raisman
Transplanted Olfactory Ensheathing Cells Promote Regeneration of Cut Adult Rat Optic Nerve Axons
J. Neurosci.,
August 27, 2003;
23(21):
7783 - 7788.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Ruitenberg, G. W. Plant, F. P. T. Hamers, J. Wortel, B. Blits, P. A. Dijkhuizen, W. H. Gispen, G. J. Boer, and J. Verhaagen
Ex Vivo Adenoviral Vector-Mediated Neurotrophin Gene Transfer to Olfactory Ensheathing Glia: Effects on Rubrospinal Tract Regeneration, Lesion Size, and Functional Recovery after Implantation in the Injured Rat Spinal Cord
J. Neurosci.,
August 6, 2003;
23(18):
7045 - 7058.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Hulsebosch
RECENT ADVANCES IN PATHOPHYSIOLOGY AND TREATMENT OF SPINAL CORD INJURY
Advan Physiol Educ,
December 1, 2002;
26(4):
238 - 255.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. H. Nash, R. C. Borke, and J. J. Anders
Ensheathing Cells and Methylprednisolone Promote Axonal Regeneration and Functional Recovery in the Lesioned Adult Rat Spinal Cord
J. Neurosci.,
August 15, 2002;
22(16):
7111 - 7120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Guntinas-Lichius, K. Wewetzer, T. L. Tomov, N. Azzolin, S. Kazemi, M. Streppel, W. F. Neiss, and D. N. Angelov
Transplantation of Olfactory Mucosa Minimizes Axonal Branching and Promotes the Recovery of Vibrissae Motor Performance after Facial Nerve Repair in Rats
J. Neurosci.,
August 15, 2002;
22(16):
7121 - 7131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Takami, M. Oudega, M. L. Bates, P. M. Wood, N. Kleitman, and M. B. Bunge
Schwann Cell But Not Olfactory Ensheathing Glia Transplants Improve Hindlimb Locomotor Performance in the Moderately Contused Adult Rat Thoracic Spinal Cord
J. Neurosci.,
August 1, 2002;
22(15):
6670 - 6681.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. W. Plant, P. F. Currier, E. P. Cuervo, M. L. Bates, Y. Pressman, M. B. Bunge, and P. M. Wood
Purified Adult Ensheathing Glia Fail to Myelinate Axons under Culture Conditions that Enable Schwann Cells to Form Myelin
J. Neurosci.,
July 15, 2002;
22(14):
6083 - 6091.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lu, F. Feron, A. Mackay-Sim, and P. M. E. Waite
Olfactory ensheathing cells promote locomotor recovery after delayed transplantation into transected spinal cord
Brain,
January 1, 2002;
125(1):
14 - 21.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Condic
Adult Neuronal Regeneration Induced by Transgenic Integrin Expression
J. Neurosci.,
July 1, 2001;
21(13):
4782 - 4788.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G. Rabchevsky and G. M. Smith
Therapeutic Interventions Following Mammalian Spinal Cord Injury
Arch Neurol,
May 1, 2001;
58(5):
721 - 726.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. F. Blakemore
Olfactory glia and CNS repair: a step in the road from proof of principle to clinical application
Brain,
August 1, 2000;
123(8):
1543 - 1544.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. C. Barnett, C. L. Alexander, Y. Iwashita, J. M. Gilson, J. Crowther, L. Clark, L. T. Dunn, V. Papanastassiou, P. G. E. Kennedy, and R. J. M. Franklin
Identification of a human olfactory ensheathing cell that can effect transplant-mediated remyelination of demyelinated CNS axons
Brain,
August 1, 2000;
123(8):
1581 - 1588.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. G. y Ribotta, J. Provencher, D. Feraboli-Lohnherr, S. Rossignol, A. Privat, and D. Orsal
Activation of Locomotion in Adult Chronic Spinal Rats Is Achieved by Transplantation of Embryonic Raphe Cells Reinnervating a Precise Lumbar Level
J. Neurosci.,
July 1, 2000;
20(13):
5144 - 5152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Aviles-Trigueros, Y. Sauve, R. D. Lund, and M. Vidal-Sanz
Selective Innervation of Retinorecipient Brainstem Nuclei by Retinal Ganglion Cell Axons Regenerating through Peripheral Nerve Grafts in Adult Rats
J. Neurosci.,
January 1, 2000;
20(1):
361 - 374.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. T. Tisay and B. Key
The Extracellular Matrix Modulates Olfactory Neurite Outgrowth on Ensheathing Cells
J. Neurosci.,
November 15, 1999;
19(22):
9890 - 9899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. J. Rosenberg, Y. D. Teng, and J. R. Wrathall
2,3-Dihydroxy-6-Nitro-7-Sulfamoyl-Benzo(f)Quinoxaline Reduces Glial Loss and Acute White Matter Pathology after Experimental Spinal Cord Contusion
J. Neurosci.,
January 1, 1999;
19(1):
464 - 475.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Li, P. M. Field, and G. Raisman
Regeneration of Adult Rat Corticospinal Axons Induced by Transplanted Olfactory Ensheathing Cells
J. Neurosci.,
December 15, 1998;
18(24):
10514 - 10524.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Pasterkamp, F. De Winter, A. J. G. D. Holtmaat, and J. Verhaagen
Evidence for a Role of the Chemorepellent Semaphorin III and Its Receptor Neuropilin-1 in the Regeneration of Primary Olfactory Axons
J. Neurosci.,
December 1, 1998;
18(23):
9962 - 9976.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
