scholarly journals Combinatorial Tissue Engineering Partially Restores Function after Spinal Cord Injury

2018 ◽  
Author(s):  
Jeffrey S. Hakim ◽  
Brian R. Rodysill ◽  
Bingkun K. Chen ◽  
Ann M. Schmeichel ◽  
Michael J. Yaszemski ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Vessel Diameter ◽  
Hydrogel Scaffolds ◽  
3 Dimensional ◽  
Cord Injury ◽  
Basement Membrane Collagen ◽  
Retrograde Axonal Tracing ◽  
Improved Function ◽  
Dose Dependent ◽  
Positively Charged

AbstractHydrogel scaffolds provide a beneficial microenvironment in transected rat spinal cord. A combinatorial biomaterials based strategy provided a microenvironment that facilitated regeneration while reducing foreign body reaction to the 3-dimensional spinal cord construct. We used poly lactic-co-glycolic acid microspheres to provide sustained release of rapamycin from Schwann cell (SC)-loaded, positively charged oligo-polyethylene glycol fumarate scaffolds. Three dose formulations of rapamycin were compared to controls in 53 rats. We observed a dose-dependent reduction in the fibrotic reaction to the scaffold and improved functional recovery over 6 weeks. Recovery was replicated in a second cohort of 28 animals that included retransection injury. Immunohistochemical and stereological analysis demonstrated that blood vessel number, surface area, vessel diameter, basement membrane collagen, and microvessel phenotype within the regenerated tissue was dependent on the presence of SCs and rapamycin. TRITC-dextran injection demonstrated enhanced perfusion into scaffold channels. Rapamycin also increased the number of descending regenerated axons, as assessed by Fast Blue retrograde axonal tracing. These results demonstrate that normalization of the neovasculature was associated with enhanced axonal regeneration and improved function after spinal cord transection.

Positively Charged Oligo[Poly(Ethylene Glycol) Fumarate] Scaffold Implantation Results in a Permissive Lesion Environment after Spinal Cord Injury in Rat

2015 ◽  
pp. 150617132638005 ◽  
Author(s):  
Jeffrey S. Hakim ◽  
Melika Esmaeili Rad ◽  
Peter J. Grahn ◽  
Bingkun K. Chen ◽  
Andrew M. Knight ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Ethylene Glycol ◽  
Poly Ethylene Glycol ◽  
Cord Injury ◽  
Poly Ethylene ◽  
Positively Charged

Dose-dependent beneficial and detrimental effects of ROCK inhibitor Y27632 on axonal sprouting and functional recovery after rat spinal cord injury

2005 ◽  
Vol 196 (2) ◽  
pp. 352-364 ◽  
Author(s):  
Carmen C.M. Chan ◽  
Kourosh Khodarahmi ◽  
Jie Liu ◽  
Darren Sutherland ◽  
Loren W. Oschipok ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Axonal Sprouting ◽  
Rat Spinal Cord ◽  
Rock Inhibitor ◽  
Cord Injury ◽  
Dose Dependent

Acute and delayed implantation of positively charged 2-hydroxyethyl methacrylate scaffolds in spinal cord injury in the rat

2008 ◽  
Vol 8 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Ales Hejcl ◽  
Lucie Urdzikova ◽  
Jiri Sedy ◽  
Petr Lesny ◽  
Martin Pradny ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treatment Group ◽  
Spinal Cord Transection ◽  
Histological Evaluation ◽  
High Water Content ◽  
Spinal Cord Tissue ◽  
Hydroxyethyl Methacrylate ◽  
Delayed Implantation ◽  
Cord Injury ◽  
Positively Charged

Object Hydrogels are nontoxic, chemically inert synthetic polymers with a high water content and large surface area that provide mechanical support for cells and axons when implanted into spinal cord tissue. Methods Macroporous hydrogels based on 2-hydroxyethyl methacrylate (HEMA) were prepared by radical copolymerization of monomers in the presence of fractionated NaCl particles. Male Wistar rats underwent complete spinal cord transection at the T-9 level. To bridge the lesion, positively charged HEMA hydrogels were implanted either immediately or 1 week after spinal cord transection; control animals were left untreated. Histological evaluation was performed 3 months after spinal cord transection to measure the volume of the pseudocyst cavities and the ingrowth of tissue elements into the hydrogels. Results The hydrogel implants adhered well to the spinal cord tissue. Histological evaluation showed ingrowth of connective tissue elements, blood vessels, neurofilaments, and Schwann cells into the hydrogels. Morphometric analysis of lesions showed a statistically significant reduction in pseudocyst volume in the treated animals compared with controls and in the delayed treatment group compared with the immediate treatment group (p < 0.001 and p < 0.05, respectively). Conclusions Positively charged HEMA hydrogels can bridge a posttraumatic spinal cord cavity and provide a scaffold for the ingrowth of regenerating axons. The results indicate that delayed implantation can be more effective than immediate reconstructive surgery.

scholarly journals Development of a decerebrate model for investigating mechanisms mediating viscero-sympathetic reflexes in the spinalized rat

2019 ◽  
Vol 316 (6) ◽  
pp. H1332-H1340 ◽  
Author(s):  
Christian A. Reynolds ◽  
Donal S. O’Leary ◽  
Cheng Ly ◽  
Scott A. Smith ◽  
Zeljka Minic
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Reflex ◽  
Autonomic Dysreflexia ◽  
Uncontrolled Hypertension ◽  
Sprague Dawley ◽  
Anesthetic Agents ◽  
Cord Injury ◽  
Sympathetic Responses ◽  
Dose Dependent

Autonomic dysreflexia (AD) often occurs in individuals living with spinal cord injury (SCI) and is characterized by uncontrolled hypertension in response to otherwise innocuous stimuli originating below the level of the spinal lesion. Visceral stimulation is a predominant cause of AD in humans and effectively replicates the phenotype in rodent models of SCI. Direct assessment of sympathetic responses to viscerosensory stimulation in spinalized animals is challenging and requires invasive surgical procedures necessitating the use of anesthesia. However, administration of anesthesia markedly affects viscerosensory reactivity, and the effects are exacerbated following spinal cord injury (SCI). Therefore, the major goal of the present study was to develop a decerebrate rodent preparation to facilitate quantification of sympathetic responses to visceral stimulation in the spinalized rat. Such a preparation enables the confounding effect of anesthesia to be eliminated. Sprague-Dawley rats were subjected to SCI at the fourth thoracic segment. Four weeks later, renal sympathetic nerve activity (RSNA) responses to visceral stimuli were quantified in urethane/chloralose-anesthetized and decerebrate preparations. Visceral stimulation was elicited via colorectal distension (CRD) for 1 min. In the decerebrate preparation, CRD produced dose-dependent increases in mean arterial pressure (MAP) and RSNA and dose-dependent decreases in heart rate (HR). These responses were significantly greater in magnitude among decerebrate animals when compared with urethane/chloralose-anesthetized controls and were markedly attenuated by the administration of urethane/chloralose anesthesia after decerebration. We conclude that the decerebrate preparation enables high-fidelity quantification of neuronal reactivity to visceral stimulation in spinalized rats. NEW & NOTEWORTHY In animal models commonly used to study spinal cord injury, quantification of sympathetic responses is particularly challenging due to the increased susceptibility of spinal reflex circuits to the anesthetic agents generally required for experimentation. This constitutes a major limitation to understanding the mechanisms mediating regionally specific neuronal responses to visceral activation in chronically spinalized animals. In the present study, we describe a spinalized, decerebrate rodent preparation that facilitates quantification of sympathetic reactivity in response to visceral stimuli following spinal cord injury. This preparation enables reliable and reproducible quantification of viscero-sympathetic reflex responses resembling those elicited in conscious animals and may provide added utility for preclinical evaluation of neuropharmacological agents for the management of autonomic dysreflexia.

RECENT ADVANCES IN PATHOPHYSIOLOGY AND TREATMENT OF SPINAL CORD INJURY

2002 ◽  
Vol 26 (4) ◽  
pp. 238-255 ◽  
Author(s):  
Claire E. Hulsebosch
Keyword(s):  
Spinal Cord ◽  
At Risk ◽  
Spinal Cord Injury ◽  
Research Effort ◽  
Basic Research ◽  
Neurite Growth ◽  
Populations At Risk ◽  
Cord Injury ◽  
Patient Will ◽  
Improved Function

Thirty years ago, patients with spinal cord injury (SCI) and their families were told “nothing can be done” to improve function. Since the SCI patient population is reaching normal life expectancy through better health care, it has become an obviously worthwhile enterprise to devote considerable research effort to SCI. Targets for intervention in SCI toward improved function have been identified using basic research approaches and can be simplified into a list: 1) reduction of edema and free-radical production, 2) rescue of neural tissue at risk of dying in secondary processes such as abnormally high extracellular glutamate concentrations, 3) control of inflammation, 4) rescue of neuronal/glial populations at risk of continued apoptosis, 5) repair of demyelination and conduction deficits, 6) promotion of neurite growth through improved extracellular environment, 7) cell replacement therapies, 8) efforts to bridge the gap with transplantation approaches, 9) efforts to retrain and relearn motor tasks, 10) restoration of lost function by electrical stimulation, and 11) relief of chronic pain syndromes. Currently, over 70 clinical trials are in progress worldwide. Consequently, in this millennium, unlike in the last, no SCI patient will have to hear “nothing can be done.”

scholarly journals Focusing on the Efficacy of Tizanidine in the Multiple Sclerosis Clinic

2001 ◽  
Vol 3 (1) ◽  
pp. 29-31
Author(s):  
Thomas F. Scott
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cerebrovascular Disease ◽  
Daily Living ◽  
Cord Injury ◽  
Improved Function ◽  
The Impact

ABSTRACT The use of tizanidine is well established in spasticity due to multiple sclerosis (MS), spinal cord injury, and cerebrovascular disease. Refinement of the use oftizanidine in these areas is ongoing. To date, most large studies have focused primarily on measurement of changes in abnormalities of tone and spasm frequency rather than changes related to improved function. More detailed studies may help to better elucidate the impact of tizanidine and other spasticity treatments on activities of daily living and overall quality of life of MS patients. (Int J MS Care. 2001; 3(1): 29–31)

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