Emerging Repair, Regeneration, and Translational Research Advances for Spinal Cord Injury

Kwon, Brian K.; Sekhon, Lali H.S.; Fehlings, Michael G.

doi:10.1097/brs.0b013e3181f3286d

Cited by 82 publications

(54 citation statements)

References 82 publications

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“…[1][2][3][4] SCI induces the mechanical destruction of the blood vessels, thereby generating a parenchymal hemorrhage (PH), which contributes to the primary injury. 5 Subsequently, the vascular damage continues to extend along the rostrocaudal axis of the spinal cord because of progressive ischemia, vasospasm, and disruption of the blood spinal cord barrier (BSCB).…”

Section: Introductionmentioning

confidence: 99%

“…Hence, there is a clear need for a safe high resolution technique to assess the vascular disruption after SCI that can be applied serially and in real time without compromising the spinal cord or necessitating animal sacrifice. 1 Various studies in clinical and experimental settings have shown that ultrasound (US) imaging can be used to visualize the PH subsequent to SCI. [15][16][17][18][19][20][21] In experimental studies, the highest frequencies used were 10-12 MHz, [18][19][20][21] but the small diameter of the rat spinal cord (3-4 mm) limited the resolution of imaging.…”

Section: Introductionmentioning

confidence: 99%

“…We have therefore developed a protocol to image the rat spinal cord with VHRUS, and the present study was performed to achieve the following three objectives: (1) to characterize the anatomical features of the intact spinal cord; (2) to characterize and quantify the vascular changes in the spinal cord during the acute and subacute phases of SCI (respectively defined as 90 min and 24 h post-SCI in our study) ; and (3) to validate VHRUS readings against several other techniques including histology and spectrophotometric analysis of hemorrhage (using Drabkin reagent) and vascular permeability (using Evans blue dye).…”

Section: Introductionmentioning

confidence: 99%

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Very High Resolution Ultrasound Imaging for Real-Time Quantitative Visualization of Vascular Disruption after Spinal Cord Injury

Soubeyrand

Badner

Vawda

et al. 2014

Journal of Neurotrauma

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Spinal cord injury (SCI) is characterized by vascular disruption with intramedullary hemorrhage, alterations in bloodspinal cord barrier integrity, and perilesional ischemia. A safe and easily applied imaging technique to quantify evolving intraspinal vascular changes after SCI is lacking. We evaluated the utility of very high resolution ultrasound (VHRUS) imaging to assess SCI-induced vascular disruption in a clinically relevant rodent model. The spinal cords of Wistar rats were lesioned at the 11th thoracic vertebra (Th11) by a 35 g 1-minute clip compression. Three-dimensional quantification of intraspinal hemorrhage using VHRUS (at an acute 90-min and subacute 24-h time point post-SCI) was compared with lesional hemoglobin and extravasated Evans blue dye measured spectrophotometrically. The anatomy of hemorrhage was comparatively assessed using VHRUS and histology. Time-lapse videos demonstrated the evolution of parenchymal hemorrhage. VHRUS accurately depicted the structural (gray and white matter) and vascular anatomy of the spinal cord (after laminectomy) and was safely repeated in the same animal. After SCI, a hyperechoic signal extended from the lesion epicenter. Significant correlations were found between VHRUS signal and hemorrhage in the acute (r = 0.88, p < 0.0001) and subacute (r = 0.85, p < 0.0001) phases and extravasated Evans blue (a measure of vascular disruption) in the subacute phase (r = 0.94, p < 0.0001). Time-lapse videos demonstrated that the expanding parenchymal hemorrhage is preceded by new perilesional hemorrhagic foci. VHRUS enables real-time quantitative live anatomical imaging of acute and subacute vascular disruption after SCI in rats. This technique has important scientific and clinical translational applications.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Very High Resolution Ultrasound Imaging for Real-Time Quantitative Visualization of Vascular Disruption after Spinal Cord Injury

Soubeyrand

Badner

Vawda

et al. 2014

Journal of Neurotrauma

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“…At the same time, it must be acknowledged that the ongoing effort to translate promising approaches from the laboratory to the bedside has not produced an FDA-approved treatment for improving neurological function, nor has a consensus standard of care been achieved. 1,2 The path to translation, the process of taking a good idea from the laboratory to a proven effective and safe treatment, has not reached its goal. This has led some to question whether we are at a critical juncture similar to that faced by stroke researchers in the 1990s, which prompted the Stroke Therapy Academic Industry Roundtable initiative to make recommendations for improving preclinical studies, 3 as well as clinical trial methodologies on the basis of analyses of the shortcomings of prior research efforts.…”

Section: Introductionmentioning

confidence: 99%

Clinical trials in spinal cord injury: lessons learned on the path to translation. The 2011 International Spinal Cord Society Sir Ludwig Guttmann Lecture

Lammertse

2012

Spinal Cord

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After three decades of clinical research on interventions to improve neurological outcomes in persons with spinal cord injury (SCI), the promise of preclinical discovery has yet to be translated into a consensus standard of care treatment. Nonetheless, SCI researchers remain hopeful that advances in preclinical discovery coupled with improved clinical trial performance will yield effective restorative treatment. This historical review of key studies in SCI over the past 30 years illustrates the progress that has been achieved in establishing a high standard in the conduct of clinical research while providing important lessons for improving trial design, conduct and reporting. Through application of these lessons, the performance of SCI trials can be improved, thereby shortening the pathway to successful translation and the development of effective therapies.

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“…A number of strategies are being investigated, and some are approaching the clinic (Kwon et al 1 for an overview). In any clinical trial treatment safety is the most important concern.…”

Section: Introductionmentioning

confidence: 99%

Neurophysiological evaluation of segmental motor neuron function of the thoracic cord in chronic SCI

et al. 2011

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Study design: Pilot study. Objectives: The aim of the study was to develop a neurophysiological method to diagnose the cranial as well as the caudal level of a complete thoracic spinal cord injury (SCI) with higher precision than today's protocols. Setting: SCI unit Karolinska University Hospital, Stockholm, Sweden. Methods: Bipolar needle electromyography was recorded in intercostal spaces of five patients with chronic, complete thoracic SCI. Tests were performed during rest, during voluntary activation and during activation of lower body spasticity. Magnetic resonance imaging (MRI) was performed in each patient according to a protocol optimized for imaging near metal implants. Results: Three distinct patterns were found in each patient. Above the lesion we found voluntary activated, normal motor unit potentials (MUPs). At the neurological level and a varying number of segments below, denervated intercostal segments with fibrillation potentials and positive sharp waves appeared. Below the neurological level, normal MUP activated in concert with lower body spasticity was found. The number of denervated segments showed a significant correlation to the length of spinal cord discontinuity on MRI (r¼0.97, Po0.05). Conclusion: Intercostal neurophysiology in combination with MRI optimized for imaging near metal implants can be used to determine the extent of a chronic complete thoracic SCI, both anatomically and functionally. The described method increases the sensitivity to detect delicate neurological changes related to the dynamic of the pathology that follows SCI and may be useful in analyzing outcome in clinical trials.

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Emerging Repair, Regeneration, and Translational Research Advances for Spinal Cord Injury

Cited by 82 publications

References 82 publications

Very High Resolution Ultrasound Imaging for Real-Time Quantitative Visualization of Vascular Disruption after Spinal Cord Injury

Very High Resolution Ultrasound Imaging for Real-Time Quantitative Visualization of Vascular Disruption after Spinal Cord Injury

Clinical trials in spinal cord injury: lessons learned on the path to translation. The 2011 International Spinal Cord Society Sir Ludwig Guttmann Lecture

Neurophysiological evaluation of segmental motor neuron function of the thoracic cord in chronic SCI

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