Evaluation of acellular and cellular nerve grafts in repair of rat peripheral nerve

1988 ◽  
Vol 68 (1) ◽  
pp. 117-123 ◽  
Author(s):  
Adarsh K. Gulati
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Axonal Regeneration ◽  
Content Type ◽  
Limited Ability ◽  
Nerve Grafts ◽  
Rat Peripheral Nerve ◽  
Fine Print

✓ Nerve grafts composed of basal lamina scaffolds and lacking viable Schwann cells have recently been shown to be effective in supporting axonal regeneration. As only short grafts were used in those studies, the present investigation was conducted to evaluate the ability of long acellular basal lamina nerve grafts and equivalent cellular grafts to support axonal regeneration for nerve gap repair. Cellular grafts consisted of nerve segments that had degenerated in situ for 4 weeks. Acellular grafting material consisted of similar segments that were repeatedly frozen and thawed to kill all cells prior to grafting. The results show that host axons can regenerate through the entire 4-cm length of cellular grafts but not through acellular basal lamina grafts. However, in the acellular grafts numerous axons were seen in the proximal 2-cm region. It is concluded that basal lamina grafts possess limited ability to support axonal regeneration. As in cellular grafts, viable Schwann cells appear to be important for regeneration to occur over longer distances.

Peripheral nerve grafts promoting central nervous system regeneration after spinal cord injury in the primate

2002 ◽  
Vol 96 (2) ◽  
pp. 197-205 ◽  
Author(s):  
Allan D. O. Levi ◽  
Hector Dancausse ◽  
Xiuming Li ◽  
Suzanne Duncan ◽  
Laura Horkey ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Peripheral Nerve ◽  
Content Type ◽  
Nerve Grafts ◽  
Cord Injury ◽  
Peripheral Nerve Grafts ◽  
Fine Print

Object. Partial restoration of hindlimb function in adult rats following spinal cord injury (SCI) has been demonstrated using a variety of transplantation techniques. The purpose of the present study was twofold: 1) to determine whether strategies designed to promote regeneration in the rat can yield similar results in the primate; and 2) to establish whether central nervous system (CNS) regeneration will influence voluntary grasping and locomotor function in the nonhuman primate. Methods. Ten cynomologus monkeys underwent T-11 laminectomy and resection of a 1-cm length of hemispinal cord. Five monkeys received six intercostal nerve autografts and fibrin glue containing acidic fibroblast growth factor (2.1 µg/ml) whereas controls underwent the identical laminectomy procedure but did not receive the nerve grafts. At 4 months postgrafting, the spinal cord—graft site was sectioned and immunostained for peripheral myelin proteins, biotinylated dextran amine, and tyrosine hydroxylase, whereas the midpoint of the graft was analyzed histologically for the total number of myelinated axons within and around the grafts. The animals underwent pre- and postoperative testing for changes in voluntary hindlimb grasping and gait. Conclusions. 1) A reproducible model of SCI in the primate was developed. 2) Spontaneous recovery of the ipsilateral hindlimb function occurred in both graft- and nongraft—treated monkeys over time without evidence of recovering the ability for voluntary tasks. 3) Regeneration of the CNS from proximal spinal axons into the peripheral nerve grafts was observed; however, the grafts did not promote regeneration beyond the lesion site. 4) The grafts significantly enhanced (p < 0.0001) the regeneration of myelinated axons into the region of the hemisected spinal cord compared with the nongrafted animals.

Peripheral nerve regeneration by transplantation of bone marrow stromal cell—derived Schwann cells in adult rats

2004 ◽  
Vol 101 (5) ◽  
pp. 806-812 ◽  
Author(s):  
Toshiro Mimura ◽  
Mari Dezawa ◽  
Hiroshi Kanno ◽  
Hajime Sawada ◽  
Isao Yamamoto
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
Adult Rats ◽  
Content Type ◽  
Alternative Method ◽  
Fine Print

Object. Bone marrow stromal cells (BMSCs) can be induced to form Schwann cells by sequentially treating the cells with β-mercaptoethanol and retinoic acid, followed by forskolin and neurotrophic factors including heregulin. In this study the authors made artificial grafts filled with BMSC-derived Schwann cells (BMSC-DSCs) and transplanted them into the transected sciatic nerve in adult rats to evaluate the potential of BMSCs as a novel alternative method of peripheral nerve regeneration. Methods. The BMSC-DSCs were suspended in Matrigel and transferred into hollow fibers (12 mm in length), which were transplanted into the transected sciatic nerve in adult Wistar rats. Six months after cell transplantation, electrophysiological evaluation and walking track analysis were performed. Results of these studies showed significant improvement in motor nerve conduction velocity and sciatic nerve functional index in the BMSC-DSC—transplanted group compared with the control group (Matrigel graft only). Immunohistochemical study data demonstrated that transplanted BMSCs labeled with retrovirus green fluorescent protein were positive for P0 and myelin-associated glycoprotein and had reconstructed nodes of Ranvier and remyelinated regenerated nerve axons. The number of regenerated axons in the axial section of the central portion of the graft was significantly greater in the transplanted group. Although BMSCs can differentiate into several types of cells, tumor formation did not occur 6 months after engraftment. Conclusions. Results in this study indicate that BMSC-DSCs have great potential to promote regeneration of peripheral nerves. The artificial graft made with BMSC-DSCs represents an alternative method for the difficult reconstruction of a long distance gap in a peripheral nerve.

Axonal regeneration after cold preservation of nerve allografts and immunosuppression with tacrolimus in mice

2002 ◽  
Vol 96 (5) ◽  
pp. 924-932 ◽  
Author(s):  
Aaron G. Grand ◽  
Terence M. Myckatyn ◽  
Susan E. Mackinnon ◽  
Daniel A. Hunter
Keyword(s):  
Peripheral Nerve ◽  
Axonal Regeneration ◽  
Positive Control ◽  
Nerve Tissue ◽  
Cold Preservation ◽  
Content Type ◽  
Therapeutic Doses ◽  
Fine Print ◽  
Better Than ◽  
Group 1

Object. The purpose of this study was to combine the immunosuppressive and neuroregenerative effects of tacrolimus (FK506) with cold preservation of peripheral nerve allografts to maximize axonal regeneration across short peripheral nerve gaps. Methods. Ninety-six male C3H mice were randomized to six groups, which were composed of animals with isografts (Group 1, positive control), allografts (Group 2, negative control), allografts treated with subtherapeutic doses of FK506 without and with cold preservation (Groups 3 and 4), and allografts treated with therapeutic doses of FK506 without and with cold preservation (Groups 5 and 6). Results were determined using walking-track data and histomorphometric measurements. Three weeks postoperatively, animals treated with therapeutic doses of FK506 after receiving cold-preserved allografts demonstrated accelerated functional recovery relative to all other groups. In addition, histomorphometric parameters in these animals (1257 ± 847 total axons, 6.7 ± 3.3% nerve tissue, 11.8 ± 6.5% neural debris, 8844 ± 4325 fibers/mm2 nerve density, and 2.53 ± 0.25 µm fiber width) were the same as or better than in all other groups. The parameters of percent nerve tissue (p < 0.016), nerve density (p < 0.038), and percent neural debris (p < 0.01) were statistically significantly better than those in all other groups, including Group 1 (isograft, positive control). Conclusions. The combination of FK506 treatment with cold preservation of nerve allografts resulted in functional and histomorphometric recovery superior to that with either modality alone.

scholarly journals Immunohistochemical, Ultrastructural and Functional Analysis of Axonal Regeneration through Peripheral Nerve Grafts Containing Schwann Cells Expressing BDNF, CNTF or NT3

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e69987 ◽  
Author(s):  
Maria João Godinho ◽  
Lip Teh ◽  
Margaret A. Pollett ◽  
Douglas Goodman ◽  
Stuart I. Hodgetts ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Axonal Regeneration ◽  
Nerve Grafts ◽  
Peripheral Nerve Grafts

Brachial plexus repair by peripheral nerve grafts directly into the spinal cord in rats

1994 ◽  
Vol 81 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Jayme Augusto Bertelli ◽  
Jean Claude Mira
Keyword(s):  
Spinal Cord ◽  
Peripheral Nerve ◽  
Brachial Plexus ◽  
Elbow Flexion ◽  
Double Labeling ◽  
Content Type ◽  
Nerve Grafts ◽  
Brachial Plexus Repair ◽  
Peripheral Nerve Grafts ◽  
Fine Print

✓ Over the years, peripheral nerve grafts, a favorable environment for the support of axonal elongation, have attracted interest as a possible means of promoting spinal cord repair. In the experiments described here, rats underwent an avulsion injury of the brachial plexus, and the musculocutaneous nerve was repaired by direct insertion of peripheral nerve grafts into the spinal cord. After varying postoperative periods, the rats were submitted to a series of behavioral tests to evaluate forelimb and hindlimb function. They also underwent retrograde double-labeling studies. Nerve grafts were harvested and processed for electronic microscopy. The biceps muscle was removed and weighed and its histology studied. After surgery, central axons effectively regenerated about 65 mm along the peripheral nerve grafts, restoring normal active elbow flexion. Forelimb movements were well coordinated in both voluntary and automatic activities. Clinical investigations showed that there were no side effects in the ipsilateral forepaw, contralateral forelimb, or either hindlimb. Regenerating axons stemmed from original motoneurons, foreign motoneurons, and even antagonist motoneurons, but this did not impair function. Ganglionic neurons from adjacent roots also sent processes to the peripheral nerve grafts.

Evaluation of histocompatibility as a factor in the repair of nerve with a frozen nerve allograft

1982 ◽  
Vol 56 (4) ◽  
pp. 550-554 ◽  
Author(s):  
Andrew A. Zalewski ◽  
Adarsh K. Gulati
Keyword(s):  
Schwann Cells ◽  
Axonal Regeneration ◽  
Immunological Tolerance ◽  
Nerve Graft ◽  
Nodose Ganglion ◽  
The Other ◽  
Clinical Use ◽  
Content Type ◽  
Transplantation Antigens ◽  
Fine Print

✓ Host axons in dogs can regenerate through a long nerve allograft provided that the allograft bears only minor transplantation antigens, and is frozen and thawed before transplantation. The authors have tried to confirm this important observation in rats. Host rats received a 4-cm fresh or frozen nerve isograft (that is, a non-antigenic nerve), or a fresh or frozen nerve allograft with cells containing only minor transplantation antigens. The results showed that after 2 and 9 months only a fresh isograft permitted many host axons to traverse its entire length. Only a few host axons grew into the proximal 1 to 2 cm of a frozen isograft or into an allograft (fresh or frozen). Because frozen grafts failed, the authors examined some specimens after 2 weeks and found that freezing killed most of the Schwann cells. On the other hand, many proliferating Schwann cells were found in 2-week fresh isografts. In addition, hosts that received a frozen nerve allograft underwent regrafting after 9 months with an isograft and allograft (of the same genotype as the original nerve allograft) of nodose ganglion. These rats accepted the isograft but rejected the allograft of ganglion. It is concluded that axonal regeneration through a long frozen nerve graft fails in rats because freezing destroys Schwann cells. Moreover, a frozen nerve allograft does not induce a state of immunological tolerance, as has been suggested, because these recipients reject a second allograft. Since the present data failed to confirm findings obtained in dogs, the clinical use of a frozen nerve allograft is not recommended.

Nerve graft immunogenicity as a factor determining axonal regeneration in the rat

1990 ◽  
Vol 72 (1) ◽  
pp. 114-122 ◽  
Author(s):  
Adarsh K. Gulati ◽  
Geoffrey P. Cole
Keyword(s):  
Basal Lamina ◽  
Peripheral Nerves ◽  
Axonal Regeneration ◽  
Nerve Repair ◽  
Inbred Strains ◽  
Nerve Tissue ◽  
Freezing And Thawing ◽  
Content Type ◽  
Repeated Freezing

✓ Acellular basal lamina grafts have recently been reported to support axonal regeneration and have been used in peripheral nerve repair. The present study was designed to determine the immunogenicity of such basal lamina allografts (grafts that are genetically different) and their potential as bridging material for nerve gap repair. Inbred strains of Fischer and Buffalo rats with known histocompatibility differences were used. Acellular grafts were prepared by repeated freezing and thawing nerve tissue predegenerated in situ for 6 weeks. Non-frozen predegenerated nerves were used as cellular grafts for comparison. Fischer rats were used as hosts and received cellular or acellular grafts obtained from Fischer (isograft, genetically identical) or Buffalo (allograft) donors. The grafts were evaluated morphologically at 1,2, 4, and 12 weeks after transplantation. The cellular isografts supported axonal regeneration best. The cellular allografts were invariably rejected and were unsuccessful or only partially successful in supporting regeneration. In contrast, acellular allografts, in spite of their mild immunogenicity were successful in supporting regeneration, as were the acellular isografts. The rate of host axonal regeneration and recovery of target muscle was reduced in acellular allografts and isografts as compared to cellular isografts. It is concluded that acellular allografts are suitable for supporting axonal regeneration and may be used to bridge gaps in injured peripheral nerves.

Percussive injury to peripheral nerve in rats

1979 ◽  
Vol 51 (2) ◽  
pp. 178-187 ◽  
Author(s):  
Peter M. Richardson ◽  
Peter K. Thomas
Keyword(s):  
Peripheral Nerve ◽  
Basal Lamina ◽  
Electron Micrographs ◽  
Wallerian Degeneration ◽  
Pathological Features ◽  
Content Type ◽  
Sciatic Nerves ◽  
Fine Print

✓ Weights were dropped on rat sciatic nerves. Teased fibers and light and electron micrographs of nerves removed between 10 minutes and 2 weeks later were examined. Axonal alterations were seen 10 minutes after injury, and subsequently interruption of axonal continuity with preservation of the basal lamina was apparent. Dissolution of myelin began within 30 minutes and progressed. At 4 days, a segment of some large fibers was devoid of myelin and, by 2 weeks, remyelination had commenced. Demyelination of a significant number of fibers was always accompanied by Wallerian degeneration of other fibers of the same nerve. Percussive injury of nerves caused a mixed lesion in which the early and late pathological features were clearly distinguishable from those following crush or compression by a cuff. Any explanation of the transient interruption of function that has been described following such an injury is at present speculative.

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