Adult rat forelimb dysfunction after dorsal cervical spinal cord injury

Onifer, Stephen M.; Burke, Darlene A.; Brooks, Donna L.; Decker, Julie A.; McClure, Natasha J.; Floyd, Andrea; Hall, Jacob; Proffitt, Bryan L.; Shields, Christopher B.; Magnuson, David S.K.

doi:10.1016/j.expneurol.2004.10.016

Cited by 65 publications

(64 citation statements)

References 35 publications

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“…These dorsal column nuclei neurons then transmit this information to thalamic neurons where it is relayed to somatosensory cortical neurons. We previously reported that adult rat upper limb SSEPS can be persistently abolished by complete cervical spinal cord dorsal columns injury (Onifer et al, 2005). Based on these findings, we hypothesized that recovery of upper limb SSEPs after incomplete cervical SCI involves neural transmission between spared cervical spinal cord dorsal column primary afferents and cuneate nuclei neurons.…”

Section: Introductionmentioning

confidence: 92%

“…As previously described (Onifer et al, 2005), 0.25mm diameter silver wires, each with a 1cm long and 0.31mm in diameter gold-plated pin soldered to one end, were wrapped around the top of sterile stainless steel self-tapping screws (#00 × 1/8). Each rat was anesthetized with a mixture of ketamine hydrochloride (50mg/kg), xylazine (5mg/kg), and acepromazine maleate (2.4mg/kg) injected intramuscularly.…”

Section: Ssepsmentioning

confidence: 99%

“…An incision was made in the skin and the median nerve of each rat was exposed. A hole was made in the epineurium, the needle of a Hamilton syringe was inserted through the hole, and 10μl of 1% unconjugated CTB (List Biological Laboratories, Inc., Campbell, CA) in 0.01M sodium phosphate buffer, pH 7.5, was slowly injected (Baker and Hagg, 2005;Onifer et al, 2005;Massey et al, 2006Massey et al, , 2007.…”

Section: Neuroanatomical Tracingmentioning

confidence: 99%

“…The brainstem sections were stained with 0.03% cytochrome C (Sigma, St. Louis, MO) and 0.05% 3,3'-diamidinobenzidine tetrahydrochloride (Sigma) as described (Wong-Riley, 1979;Crockett et al, 1993) to see the electrode tracks in the dorsal column nuclei. The spinal cord sections were stained with 0.5% cresyl violet (Sigma) and 25% eosin y (Sigma) solutions as described (Onifer et al, 2005) to view the morphology of the injury site. Brainstem sections and C8 spinal cord sections also were immunostained for CTB as described (Massey et al, 2006(Massey et al, , 2007 to view primary afferent terminals within the cuneate nuclei and the dorsal horn, so as to determine the success of the neuroanatomical tracing procedure.…”

Section: Histology and Microscopymentioning

confidence: 99%

“…Damage to the adult human cervical spinal cord dorsal columns leads to sensory dysfunctions of the upper limbs as evidenced by transient exaggeration or abolishment of the cutaneous sensations of fine touch, vibration, and proprioception (for a review, see York, 1985;Nathan et al, 1986). Similarly (Metz et al, 2000;Norenberg et al, 2004), transient and persistent upper limb cutaneous sensation dysfunctions occur in adult rats with damage to their cervical spinal cord dorsal columns (Schrimsher and Reier, 1993;McKenna and Whishaw, 1999;Ballerman et al, 2001a,b;Onifer et al, 2005;Kanagal and Muir, 2007). Abolished upper limb somatosensory evoked potentials (SSEPs) also can recover spontaneously in persons with incomplete cervical SCI (Curt and Dietz, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

Onifer

Nunn

Decker

et al. 2007

Experimental Neurology

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Varying degrees of neurologic function spontaneously recovers in humans and animals during the days and months after spinal cord injury (SCI). For example, abolished upper limb somatosensory potentials (SSEPS) and cutaneous sensations can recover in persons post-contusive cervical SCI. To maximize recovery and the development/evaluation of repair strategies, a better understanding of the anatomical locations and physiological processes underlying spontaneous recovery after SCI is needed. As an initial step, the present study examined whether recovery of upper limb SSEPs after contusive cervical SCI was due to the integrity of some spared dorsal column primary afferents that terminate within the cuneate nucleus and not one of several alternate routes. C5-C6 contusions were performed on male adult rats. Electrophysiological techniques were used in the same rat to determine forelimb evoked neuronal responses in both cortex (SSEPS) and the cuneate nucleus (terminal extracellular recordings). SSEPs were not evoked 2 days post-SCI but were found at 7 days and beyond, with an observed change in latencies between 7 and 14 days (suggestive of spared axon remyelination). Forelimb evoked activity in the cuneate nucleus at 15 but not 3 days post-injury occurred despite dorsal column damage throughout the cervical injury (as seen histologically). Neuroanatomical tracing (using 1% unconjugated cholera toxin B subunit) confirmed that upper limb primary afferent terminals remained within the cuneate nuclei. Taken together, these results indicate 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. NIH Public Access

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Section: Introductionmentioning

confidence: 92%

Section: Ssepsmentioning

confidence: 99%

Section: Neuroanatomical Tracingmentioning

confidence: 99%

Section: Histology and Microscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

Onifer

Nunn

Decker

et al. 2007

Experimental Neurology

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The Dorsal Column Lesion Model of Spinal Cord Injury and Its Use in Deciphering the Neuron‐Intrinsic Injury Response

Attwell

Zwieten

Verhaagen

et al. 2018

Developmental Neurobiology

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The neuron‐intrinsic response to axonal injury differs markedly between neurons of the peripheral and central nervous system. Following a peripheral lesion, a robust axonal growth program is initiated, whereas neurons of the central nervous system do not mount an effective regenerative response. Increasing the neuron‐intrinsic regenerative response would therefore be one way to promote axonal regeneration in the injured central nervous system. The large‐diameter sensory neurons located in the dorsal root ganglia are pseudo‐unipolar neurons that project one axon branch into the spinal cord, and, via the dorsal column to the brain stem, and a peripheral process to the muscles and skin. Dorsal root ganglion neurons are ideally suited to study the neuron‐intrinsic injury response because they exhibit a successful growth response following peripheral axotomy, while they fail to do so after a lesion of the central branch in the dorsal column. The dorsal column injury model allows the neuron‐intrinsic regeneration response to be studied in the context of a spinal cord injury. Here we will discuss the advantages and disadvantages of this model. We describe the surgical methods used to implement a lesion of the ascending fibers, the anatomy of the sensory afferent pathways and anatomical, electrophysiological, and behavioral techniques to quantify regeneration and functional recovery. Subsequently we review the results of experimental interventions in the dorsal column lesion model, with an emphasis on the molecular mechanisms that govern the neuron‐intrinsic injury response and manipulations of these after central axotomy. Finally, we highlight a number of recent advances that will have an impact on the design of future studies in this spinal cord injury model, including the continued development of adeno‐associated viral vectors likely to improve the genetic manipulation of dorsal root ganglion neurons and the use of tissue clearing techniques enabling 3D reconstruction of regenerating axon tracts. © 2018 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 00: 000–000, 2018

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Experimental Laceration Spinal Cord Injury Model

Shields

2009

Springer Protocols Handbooks

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Adult rat forelimb dysfunction after dorsal cervical spinal cord injury

Cited by 65 publications

References 35 publications

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

The Dorsal Column Lesion Model of Spinal Cord Injury and Its Use in Deciphering the Neuron‐Intrinsic Injury Response

Experimental Laceration Spinal Cord Injury Model

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