TY - JOUR
T1 - Dissociated predegenerated peripheral nerve transplants for spinal cord injury repair
T2 - A comprehensive assessment of their effects on regeneration and functional recovery compared to schwann cell transplants
AU - Hill, Caitlin E.
AU - Brodak, Danika M.
AU - Bartlett Bunge, Mary
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/8/10
Y1 - 2012/8/10
N2 - Several recent studies suggest that predegenerated nerves (PDNs) or dissociated PDNs (dPDNs) can improve behavioral and histological outcomes following transplantation into the injured rat spinal cord. In the current study we tested the efficacy of dPDN transplantation by grafting cells isolated from the sciatic nerve 7 days after crush. We did not replicate one study, but rather assessed what appeared, based on five published reports, to be a reported robust effect of dPDN grafts on corticospinal tract (CST) regeneration and locomotor recovery. Using a standardized rodent spinal cord injury model (200 kD IH contusion) and transplantation procedure (injection of GFP+ cells 7 days post-SCI), we demonstrate that dPDN grafts survive within the injured spinal cord and promote the ingrowth of axons to a similar extent as purified Schwann cell (SC) grafts. We also demonstrate for the first time that while both dPDN and SC grafts promote the ingrowth of CGRP axons, neither graft results in mechanical or thermal hyperalgesia. Unlike previous studies, dPDN grafts did not promote long-distance axonal growth of CST axons, brainstem spinal axons, or ascending dorsal column sensory axons. Moreover, using a battery of locomotor tests (Basso Beattie Bresnahan [BBB] score, BBB subscore, inked footprint, Catwalk, and ladderwalk), we failed to detect any beneficial effects of dPDN transplantation on the recovery of locomotor function after SCI. We conclude that dPDN transplants are not sufficient to promote CST regeneration or locomotor recovery after SCI.
AB - Several recent studies suggest that predegenerated nerves (PDNs) or dissociated PDNs (dPDNs) can improve behavioral and histological outcomes following transplantation into the injured rat spinal cord. In the current study we tested the efficacy of dPDN transplantation by grafting cells isolated from the sciatic nerve 7 days after crush. We did not replicate one study, but rather assessed what appeared, based on five published reports, to be a reported robust effect of dPDN grafts on corticospinal tract (CST) regeneration and locomotor recovery. Using a standardized rodent spinal cord injury model (200 kD IH contusion) and transplantation procedure (injection of GFP+ cells 7 days post-SCI), we demonstrate that dPDN grafts survive within the injured spinal cord and promote the ingrowth of axons to a similar extent as purified Schwann cell (SC) grafts. We also demonstrate for the first time that while both dPDN and SC grafts promote the ingrowth of CGRP axons, neither graft results in mechanical or thermal hyperalgesia. Unlike previous studies, dPDN grafts did not promote long-distance axonal growth of CST axons, brainstem spinal axons, or ascending dorsal column sensory axons. Moreover, using a battery of locomotor tests (Basso Beattie Bresnahan [BBB] score, BBB subscore, inked footprint, Catwalk, and ladderwalk), we failed to detect any beneficial effects of dPDN transplantation on the recovery of locomotor function after SCI. We conclude that dPDN transplants are not sufficient to promote CST regeneration or locomotor recovery after SCI.
KW - axon regeneration
KW - Basso Beattie Bresnahan score
KW - Catwalk
KW - Hargreaves
KW - ladderwalk
KW - peripheral nerve
KW - Schwann cells
KW - spinal cord injury
KW - transplant
KW - von Frey
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U2 - 10.1089/neu.2012.2377
DO - 10.1089/neu.2012.2377
M3 - Article
C2 - 22655857
AN - SCOPUS:84865230299
VL - 29
SP - 2226
EP - 2243
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
SN - 0897-7151
IS - 12
ER -