Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat

Cao, Qilin; Zhang, Yi Ping; Iannotti, Christopher A.; DeVries, William H.; Xu, Xiao–Ming; Shields, Christopher B.; Whittemore, Scott R.

doi:10.1016/j.expneurol.2004.08.026

Cited by 158 publications

(135 citation statements)

References 58 publications

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“…Previously, we found that infusion of a recombinant sialidase to the site of a peripheral nerve graft enhanced outgrowth of CNS axons into the graft (19). Here, we report that sialidase enhances motor and autonomic functional recovery and stimulates axon outgrowth after spinal cord contusion injury in the rat, an animal model of the most common type of spinal cord injury in humans (20).…”

mentioning

confidence: 84%

“…A laminectomy was performed at T9 to accommodate the tip of an Infinite Horizon impactor (Precision Systems). The spine was stabilized with clamps at the T8 and T10 vertebrae, and a 175-kdyn contusion was delivered at T9 (20). Sialidase solution (50 μL) or carrier was delivered to the injury site via the intrathecal catheter and the proximal end of the catheter was connected to an s.c. osmotic pump (200 μL, 0.5 μL/h, 14 d; Alzet/Durect) prefilled with the same solution.…”

Section: Methodsmentioning

confidence: 99%

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Sialidase enhances recovery from spinal cord contusion injury

Mountney¹,

Zahner

Lorenzini³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Axons fail to regenerate in the injured spinal cord, limiting motor and autonomic recovery and contributing to long-term morbidity. Endogenous inhibitors, including those on residual myelin, contribute to regeneration failure. One inhibitor, myelin-associated glycoprotein (MAG), binds to sialoglycans and other receptors on axons. MAG inhibition of axon outgrowth in some neurons is reversed by treatment with sialidase, an enzyme that hydrolyzes sialic acids and eliminates MAG-sialoglycan binding. We delivered recombinant sialidase intrathecally to rats following a spinal cord contusive injury. Sialidase (or saline solution) was infused to the injury site continuously for 2 wk and then motor behavior, autonomic physiology, and anatomic outcomes were determined 3 wk later. Sialidase treatment significantly enhanced hindlimb motor function, improved bulbospinally mediated autonomic reflexes, and increased axon sprouting. These findings validate sialoglycans as therapeutic targets and sialidase as a candidate therapy for spinal cord injury.axon regeneration | ganglioside | myelin-associated glycoprotein | serotonergic axons | sialoglycan

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mentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Sialidase enhances recovery from spinal cord contusion injury

Mountney¹,

Zahner

Lorenzini³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition to potassium channel blockers, cell transplantation with the purpose of remyelinating fibers has been one of the main therapeutic approaches to improve function after SCI (Li et al, 1997;Akiyama et al, 2002;Cao et al, 2005;Cummings et al, 2005;Lepore and Fischer, 2005). Remyelination by transplanted cells of different kinds is readily observable, but only if such transplants are delivered early, namely before 3 weeks after SCI Karimi-Abdolrezaee et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Rodent models of SCI reveal electrophysiological and morphological signs of demyelinated axons (Gledhill et al, 1973;Blakemore, 1974;Gledhill and McDonald, 1977;Blight, 1985;Gensert and Goldman, 1997;Cao et al, 2005). Initial demyelination is thought to be caused by necrosis of oligodendrocytes; however, it is not exactly clear what causes prolonged oligodendrocyte death weeks and months after injury (Blight, 1985;Crowe et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…Experimental strategies such as cell transplantation designed to preserve myelin or to induce remyelination have lead to successful improvements in function after spinal cord injury (SCI) if administered in acute or subacute phases after SCI (Li et al, 1997;Akiyama et al, 2002;Cao et al, 2005;Cummings et al, 2005;Keirstead et al, 2005;Lepore and Fischer, 2005). However, remyelination strategies fails if transplants are delivered chronically after SCI Karimi-Abdolrezaee et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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No Evidence for Chronic Demyelination in Spared Axons after Spinal Cord Injury in a Mouse

Lašienė¹,

Shupe²,

Perlmutter³

et al. 2008

J. Neurosci.

125

137

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The pattern of remyelination after traumatic spinal cord injury remains elusive, with animal and human studies reporting partial to complete demyelination followed by incomplete remyelination. In the present study, we found that spared rubrospinal tract (RST) axons of passage traced with actively transported dextrans and examined caudally to the lesion 12 weeks after mouse spinal cord contusion injury were fully remyelinated. Spared axons exhibited a marginally reduced myelin thickness and significantly shorter internodes. CASPR (contactin-associated protein) and K v 1.2 channels were used to identify internodes and paranodal protein distribution properties were used as an index of myelin integrity. This is the first time the CNS myelin internode length was measured in a mouse. To better understand the significance of shortened internodes and thinner myelin in spared axons, we modeled conduction properties using McIntyre's et al. model of myelinated axons. Mathematical modeling predicted a 21% decrease in the conduction velocity of remyelinated RST axons attributable to shortened internodes. To determine whether demyelination could be present on axons exhibiting a pathological transport system, we used the retroviral reporter system. Virally delivered green fluorescent protein unveiled a small population of dystrophic RST axons that persist chronically with evident demyelination or abnormal remyelination. Collectively, these data show that lasting demyelination in spared axons is rare and that remyelination of axons of passage occurs in the chronically injured mouse spinal cord.

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Correlation between electrophysiological properties, morphological maturation, and olig gene changes during postnatal motor tract development

Cai

Shields

Zhang

et al. 2013

Developmental Neurobiology

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Background Functional maturation of the nervous system in postnatal (PN) animals is a progressive process that may be assessed using evoked potentials of the auditory, visual, or somatosensory systems. This study investigated electrophysiological and histological changes as well as alterations of myelin relevant proteins of descending motor tracts in rat pups. MEP responses were recorded bi-weekly from postnatal (PN) week-1 to week-9 (adult). Results MEP latencies in PN week-1 rats averaged 23.7 milliseconds and became shorter during early maturation, stabilizing at 6.6 milliseconds at PN week-4. During maturation there was a rapid increase in the conduction velocity (CV). The CV increased from 2.8 ± 0.2 at PN week-1 to 35.2 ± 3.1 mm/ms at PN week-8 which represented functional maturation. Histology of the spinal cord and sciatic nerves revealed progressive axonal myelination. Expression of the oligodendrocyte precursor markers PDGFRα and NG2 were gradually down-regulated in spinal cords, and myelin-relevant proteins such as GalC, CNP, and MBP were increased during maturation. Oligodendrocyte-lineage markers Olig2 and MOG, specifically expressed in myelinated oligodendrocytes, peaked at approximately PN week-3 and were down-regulated thereafter. A similar expression pattern was also observed in neurofilament M/H subunits (NF-M/H). Noticeably, NF-M/H was extensively phosphorylated in adult spinal cords but not in neonatal spinal cords, suggesting an increase in axon diameter and myelin formation. Ultra-structural morphology of axon and myelin sheaths in the ventrolateral funiculus (VLF) showed axon myelination of the VLF axons (99.3%) at PN week-2, while only 44.6% were sheathed at PN week-1. Furthermore, increased axon diameter and myelin thickness in both the VLF and sciatic nerves were highly correlated to the CV (rs>0.95). Conclusions Results from this study indicate that MEPs may be a predicator for the morphological maturity and integrity of myelinated axons in descending motor tracts.

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Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat

Cited by 158 publications

References 58 publications

Sialidase enhances recovery from spinal cord contusion injury

Sialidase enhances recovery from spinal cord contusion injury

No Evidence for Chronic Demyelination in Spared Axons after Spinal Cord Injury in a Mouse

Correlation between electrophysiological properties, morphological maturation, and olig gene changes during postnatal motor tract development

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