Direct evidence of primary afferent sprouting in distant segments following spinal cord injury in the rat: colocalization of GAP-43 and CGRP

Ondarza, Adrianne B; Ye, Zaiming; Hulsebosch, Claire E.

doi:10.1016/j.expneurol.2003.07.002

Cited by 136 publications

(97 citation statements)

References 50 publications

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“…In the current study, CGRP-positive fibers that sprout into the center of the deafferented region remain within the normal lamination boundary, in contrast to reports of sprouting C-fibers expanding into novel laminae in rats (Ondarza et al, 2003;Runyan et al, 2005). These findings suggest that signals regulating the pattern and extent of primary afferent sprouting may differ between species.…”

Section: Peptidergic and Nonpeptidergic Axonal Sprouting In Wild-typecontrasting

confidence: 91%

“…As in previous acute and chronic rhizotomy studies, we found that CGRP labels sprouting primary afferents in adult mice (McNeill and Hulsebosch, 1987;McNeill et al, 1990), but in a somewhat different pattern than detected in rats (Ondarza et al, 2003;Runyan et al, 2005). In the current study, CGRP-positive fibers that sprout into the center of the deafferented region remain within the normal lamination boundary, in contrast to reports of sprouting C-fibers expanding into novel laminae in rats (Ondarza et al, 2003;Runyan et al, 2005).…”

Section: Peptidergic and Nonpeptidergic Axonal Sprouting In Wild-typesupporting

confidence: 84%

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L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

Runyan

Roy²,

Zhong³

et al. 2007

Neuroscience

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L1 is a cell adhesion molecule associated with axonal outgrowth and fasciculation during spinal cord development and may reiterate its developmental role in adults following injury; L1 is upregulated on certain sprouting and regenerating axons in adults, but it is unclear if L1 expression is necessary for, or contributes to, regrowth of axons. This study asks if L1 is required for small-diameter primary afferents to sprout by conducting unilateral dorsal rhizotomies (6 segments; T10-L2) on both wildtype and L1 mutant mice. First we determined that L1 co-localizes substantially with the peptidergic (calcitonin gene-related peptide; CGRP) but minimally with the nonpeptidergic (isolectin B4; IB4) primary afferents in intact wild-type and L1 mutant mice. However, we encountered a complication using IB4 to identify primary afferents post-rhizotomy; we detected extensive abnormal IB4 expression in the dorsal horn and dorsal columns. Much of this aberrant IB4 labeling is associated with fibrous astrocytes and microglia. Five days after dorsal rhizotomy a large decrease in peptidergic and nonpeptidergic afferents is evident on the deafferented side in both wild-type and L1 mutants. Three months after surgery the peptidergic primary afferents sprouted into the center of the denervated dorsal horn in both wild-type and mutant mice, and quantitative analyses confirmed a sprouting density of similar magnitude in both genotypes. In contrast, we did not detect sprouting in the nonpeptidergic primary afferents in either genotype. These results suggest that the absence of L1 neither diminishes nor enhances sprouting of peptidergic small-diameter primary afferent axons following a dorsal rhizotomy. Keywordscell adhesion molecule; denervated; IB4; CGRP; nociceptors; rhizotomy The cell adhesion molecule L1 (L1 CAM) is an axonal glycoprotein and a member of the immunoglobulin superfamily (Kamiguchi et al., 1997). L1 plays a role in axonal outgrowth, fasciculation, and guidance during spinal cord development (Stallcup et al., 1985;Jessell, 1988;Stoeckli and Landmesser, 1995;Orlino et al., 2000;Tran and Phelps, 2000;Akopians et al., 2003) through homophilic and various heterophilic binding partners such as integrins (αVβ3 and α5β1) and the fibroblast growth factor receptor (Kamiguchi and Lemmon, 1997 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Lemmon, 1997;Castellani et al., 2000). NIH Public AccessMutations in X-linked L1 in humans cause major developmental errors and result in a group of symptoms that include corpus callosum hypoplasia, spastic paraplegia and hydrocephalus (Fran...

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Section: Peptidergic and Nonpeptidergic Axonal Sprouting In Wild-typecontrasting

confidence: 91%

Section: Peptidergic and Nonpeptidergic Axonal Sprouting In Wild-typesupporting

confidence: 84%

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

Runyan

Roy²,

Zhong³

et al. 2007

Neuroscience

View full text Add to dashboard Cite

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“…For example, sprouting of peripheral fibers has been noted after SCI [29], likely impacting nociception [33], autonomic function [28,37], and proprioception [17]. Multiple studies have begun to elucidate a role for plasticity in various neurotransmitter systems in the lumbar spinal cord after SCI and how those changes relate to changes in motor performance [14,24,32,34].…”

Section: Potential Role Of State-dependent Spinal Plasticity In Acutementioning

confidence: 99%

Two chronic motor training paradigms differentially influence acute instrumental learning in spinally transected rats

Bigbee

Crown

Ferguson

et al. 2007

Behavioural Brain Research

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The effect of two chronic motor training paradigms on the ability of the lumbar spinal cord to perform an acute instrumental learning task was examined in neonatally (postnatal day 5; P5) spinal cord transected (i.e., spinal) rats. At ∼P30, rats began either unipedal hindlimb stand training (Stand-Tr; 20-25 min/day, 5 days/wk), or bipedal hindlimb step training (Step-Tr; 20 min/day; 5 days/wk) for 7 wks. Non-trained spinal rats (Non-Tr) served as controls. After 7 wks all groups were tested on the flexor-biased instrumental learning paradigm. We hypothesized that 1) Step-Tr rats would exhibit an increased capacity to learn the flexor-biased task relative to Non-Tr subjects, as locomotion involves repetitive training of the tibialis anterior (TA), the ankle flexor whose activation is important for successful instrumental learning, and 2) Stand-Tr rats would exhibit a deficit in acute motor learning, as unipedal training activates the ipsilateral ankle extensors, but not flexors. Results showed no differences in acute learning potential between Non-Tr and Step-Tr rats, while the Stand-Tr group showed a reduced capacity to learn the acute task. Further investigation of the Stand-Tr group showed that, while both the ipsilateral and contralateral hindlimbs were significantly impaired in their acute learning potential, the contralateral, untrained hindlimbs exhibited significantly greater learning deficits. These results suggest that different types of chronic peripheral input may have a significant impact on the ability to learn a novel motor task, and demonstrate the potential for experiencedependent plasticity in the spinal cord in the absence of supraspinal connectivity.

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“…[18][19][20] In uninjured spinal cord, CGRP immunopositive axons convey pain and temperature information, synapsing on second order neurons within lamina I and II of the spinal dorsal horns ( Figure 1). [21][22][23] These second order axons cross at the level of the spinal cord within the anterior spinal commissure and ascend through the spinothalamic tract to the thalamus. It has been shown that in animals with SCI, CGRP-containing fibers sprout into deeper laminas.…”

Section: Introductionmentioning

confidence: 99%

Calcitonin gene-related peptide immunoreactivity in chronic human spinal cord injury

2007

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Study Design: Histopathological study of the human spinal cord. Setting: International Collaboration on Repair Discoveries, Vancouver, BC, Canada. Rationale: In animals, primary dorsal root afferent fibers, which are immunoreactive for calcitonin gene-related peptide (CGRP), sprout following spinal cord injury (SCI) into deeper laminas of the dorsal horn below the level of injury. It has been suggested that this aberrant sprouting plays a role in altering cardiovascular control after SCI and could be responsible for life-threatening episodes of autonomic dysreflexia (AD). Objectives: To observe the changes of CGRP distribution after SCI and compare the differences between normal and injured human spinal cord. Methods: Upper thoracic segments from individuals with chronic cervical SCI (n ¼ 4) and individuals with intact spinal cords (n ¼ 5) were processed immunocytochemically to identify CGRP fibers and histologically to identify the severity of degeneration. Results: Semiquantitative analysis showed a significant increase in CGRP immunoreactivity in the dorsal horns of individuals with chronic SCI (Po0.001). Furthermore, one of the SCI individuals in this study displaying significant CGRP sprouting had well documented episodes of AD. Conclusions: Our observations suggest that SCI in humans results in significant sprouting of CGRP fibers. This aberrant sprouting of sensory fibers could contribute to the abnormal cardiovascular control and pain commonly observed following chronic human SCI.

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Direct evidence of primary afferent sprouting in distant segments following spinal cord injury in the rat: colocalization of GAP-43 and CGRP

Cited by 136 publications

References 50 publications

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

Two chronic motor training paradigms differentially influence acute instrumental learning in spinally transected rats

Calcitonin gene-related peptide immunoreactivity in chronic human spinal cord injury

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