Reconstruction of the transected cat spinal cord following NeuroGel implantation: axonal tracing, immunohistochemical and ultrastructural studies.
This study examined the ability of NeuroGel, a biocompatible porous poly [N-(2-hydroxypropyl) methacrylamide] hydrogel, to establish a permissive environment across a 3 mm gap in the cat spinal cord in order to promote tissue reconstitution and axonal regeneration across the lesion. Animals with NeuroGel implants were compared to transection-only controls and observed for 21 months. The hydrogel formed a stable bridge between the cord segments. Six months after reconstructive surgery, it was densely infiltrated by a reparative tissue composed of glial cells, capillary vessels and axonal fibres. Axonal labelling and double immunostaining for neurofilaments and myelin basic protein, showed that descending supraspinal axons of the ventral funiculus and afferent fibres of the dorsal column regenerated across the reconstructed lesion. Fifteen months after reconstructive surgery, axons had grown, at least, 12 mm into the distal cord tissue, and in the rostral cord there was labelling of neurons of the intermediate gray matter. Electron microscopy showed that after 9 months, most of the regenerating axons were myelinated, principally by Schwann cells. Newly formed neurons presumably from precursor cells of the ependyma and/or migrating neurons were observed within the reparative tissue after 21 months. Results indicate that functional deficit, as assessed by treadmill training, and morphological changes following double transection of the spinal cord can be modified by the implantation of NeuroGel. This technology offers the potential to promote the formation of a neural tissue equivalent via a reparative neohistogenesis process, that facilitates and supports regenerative growth of axons.
Woerly
S
S
Organogel Canada Ltée, 1400 Parc Technologique Blvd, G1P 4R7, Québec, Canada. woerlyst@organogel.com
Doan
V D
VD
Sosa
N
N
de Vellis
J
J
Espinosa
A
A
D020341:Absorbable Implants; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D019771:Axotomy / Q000009:adverse effects; D001710:Biotin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002415:Cats; D003911:Dextrans / Q000493:pharmacokinetics; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020100:Hydrogels / Q000494:pharmacology*; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000379:methods / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000601:surgery*; D016896:Treatment Outcome; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate / Q000493:pharmacokinetics
D003911:Dextrans; D005904:Glial Fibrillary Acidic Protein; D020100:Hydrogels; D016900:Neurofilament Proteins; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; C076397:biotinylated dextran amine; D001710:Biotin