L1 CAM expression is increased surrounding the lesion site in rats with complete spinal cord transection as neonates

Kubasak, Marc D.; Hedlund, Eva; Roy, Roland R.; Carpenter, Ellen M.; Edgerton, V. Reggie; Phelps, Patricia E.

doi:10.1016/j.expneurol.2005.02.013

Cited by 26 publications

(29 citation statements)

References 55 publications

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“…In the present study, a fourfold increase in weight-bearing steps was observed in the rats that received the large amount of WSTT relative to untrained rats, and this improvement was in line with previous studies of WSTT in neonatal ST rats (Cha et al, 2007;Kubasak et al, 2005;Petruska et al, 2007). Imposing a small amount of WSTT resulted in a twofold increase in the number of weightbearing steps, but fewer of these rats were capable of consistent weight-bearing stepping compared to rats that received The bars represent the average for each group (n = 5, 6, and 5 for the 0, 100, and 1000 groups respectively).…”

Section: Wstt and Locomotor Recovery In St Animalssupporting

confidence: 79%

Differential Effects of Low versus High Amounts of Weight Supported Treadmill Training in Spinally Transected Rats

Leon

See

Chow

2011

Journal of Neurotrauma

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Intensive weight-supported treadmill training (WSTT)improves locomotor function following spinal cord injury. Because of a number of factors, undergoing intensive sessions of training may not be feasible. Whether reduced amounts of training are sufficient to enhance spinal plasticity to a level that is necessary for improving function is not known. The focus of the present study was to assess differences in recovery of locomotor function and spinal plasticity as a function of the amount of steps taken during WSTT in a rodent model of spinal cord injury. Rats were spinally transected at 5 days of age. When they reached 28 days of age, a robotic system was used to implement a weight-supported treadmill training program of either 100 or 1000 steps/training session daily for 4 weeks. Antibodies for brain-derived neurotrophic factor (BDNF), TrkB, and the pre-synaptic marker, synaptophysin, were used to examine the expression of these proteins in the ventral horn of the lumbar spinal cord. Rats that received weight-supported treadmill training performed better stepping relative to untrained rats, but only the rats that received 1000 steps/training session recovered locomotor function that resembled normal patterns. Only the rats that received 1000 steps/training session recovered normal levels of synaptophysin immunoreactivity around motor neurons. Weight-supported treadmill training consisting of either 100 or 1000 steps/ training session increased BDNF immunoreactivity in the ventral horn of the lumbar spinal cord. TrkB expression in the ventral horn was not affected by spinal cord transection or weight-supported treadmill training. Synaptophysin expression, but not BDNF or TrkB expression was correlated with the recovery of stepping function. These findings suggested that a large amount of weight-supported treadmill training was necessary for restoring synaptic connections to motor neurons within the locomotor generating circuitry. Although a large amount of training was best for recovery, small amounts of training were associated with incremental gains in function and increased BDNF levels.

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Section: Wstt and Locomotor Recovery In St Animalssupporting

confidence: 79%

Differential Effects of Low versus High Amounts of Weight Supported Treadmill Training in Spinally Transected Rats

Leon

See

Chow

2011

Journal of Neurotrauma

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“…it is downregulated on myelinated axons and re-expressed in regenerating axons after spinal cord injury [64,65] . Exogenous L1CAM is beneficial in promoting axon growth and functional recovery after spinal cord injury [66] and optic nerve lesion [67] and is involved in the regenerative growth of Purkinje cell axons in vivo [68] .…”

Section: Cell Adhesion Moleculesmentioning

confidence: 99%

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

Zhang

Guo

2013

Neurosci. Bull.

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Multiple sclerosis (MS) is a chronic and devastating autoimmune demyelinating disease of the central nervous system. With the increased understanding of the pathophysiology of this disease in the past two decades, many disease-modifying therapies that primarily target adaptive immunity have been shown to prevent exacerbations and new lesions in patients with relapsing-remitting MS. However, these therapies only have limited efficacy on the progression of disability. Increasing evidence has pointed to innate immunity, axonal damage and neuronal loss as important contributors to disease progression. Remyelination of denuded axons is considered an effective way to protect neurons from damage and to restore neuronal function. The identification of several key molecules and pathways controlling the differentiation of oligodendrocyte progenitor cells and myelination has yielded clues for the development of drug candidates that directly target remyelination and neuroprotection. The long-term efficacy of this strategy remains to be evaluated in clinical trials. Here, we provide an overview of current and emerging therapeutic concepts, with a focus on the opportunities and challenges for the remyelination approach to the treatment of MS.

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“…L1 is expressed on sprouting primary afferents after dorsal rhizotomy in rats (Runyan et al, 2005) and is implicated as a possible factor for axonal growth following injury to the nervous system (Styren et al, 1995;Aubert et al, 1998;Brook et al, 2000;Roonprapunt et al, 2003;Kubasak et al, 2005;Chen et al, 2007). If L1 is necessary for primary afferent sprouting, we would expect to see little or no sprouting in its absence.…”

Section: L1 Is Not Required For Cgrp-positive Afferent Sproutingmentioning

confidence: 99%

“…L1 is among several growth-associated genes that are upregulated by neurons after nervous system injury (Daniloff, et al, 1986;Chaisuksunt et al, 2000;Kubasak et al, 2005), however its effects are contradictory. Some studies suggest that L1 CAM reiterates its developmental role following injury, as it is upregulated on sprouting and regenerating axons in many models (Daniloff et al, 1986;Martini and Schachner, 1988;Miragall et al, 1989;Styren et al, 1995;Chalmers et al, 1996;Brook et al, 2000;Kubasak et al, 2005;Chen et al, 2007). However, other studies conclude that L1 is not essential for axonal growth into the injury site (Jakeman et al, 2006) and that nerve growth factor-induced sprouting is even reduced by co-expression of L1 (Chaudhry et al, 2006).…”

mentioning

confidence: 99%

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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L1 CAM expression is increased surrounding the lesion site in rats with complete spinal cord transection as neonates

Cited by 26 publications

References 55 publications

Differential Effects of Low versus High Amounts of Weight Supported Treadmill Training in Spinally Transected Rats

Differential Effects of Low versus High Amounts of Weight Supported Treadmill Training in Spinally Transected Rats

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

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

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