Evaluation of in situ gelling chitosan-PEG copolymer for use in the spinal cord

2018 ◽  
Vol 33 (3) ◽  
pp. 435-446 ◽  
Author(s):  
Ashley E Mohrman ◽  
Mahmoud Farrag ◽  
Rachel K Grimm ◽  
Nic D Leipzig
Keyword(s):  
Spinal Cord ◽  
Polyethylene Glycol ◽  
Spinal Cord Injuries ◽  
Similar Response ◽  
Cellular Delivery ◽  
Thiolated Chitosan ◽  
Cord Injury ◽  
In Situ Gelling

The goal of the present work was to characterize a hydrogel material for localized spinal cord delivery. To address spinal cord injuries, an injectable in situ gelling system was tested utilizing a simple, effective, and rapid cross-linking method via Michael addition. Thiolated chitosan material and maleimide-terminated polyethylene glycol material were mixed to form a hydrogel and evaluated in vitro and in vivo. Three distinct thiolated chitosan precursors were made by varying reaction conditions; a modification of chitosan with Traut’s reagent (2-iminothiolane) displayed the most attractive hydrogel properties once mixed with polyethylene glycol. The final hydrogel chosen for animal testing had a swelling ratio (Q) of 57.5 ± 3.4 and elastic modulus of 378 ± 72 Pa. After confirming low cellular toxicity in vitro, the hydrogel was injected into the spinal cord of rats for 1 and 2 weeks to assess host reaction. The rats displayed no overt functional deficits due to injection following initial surgical recovery and throughout the 2-week period after for both the saline-injected sham group and hydrogel-injected group. The saline and hydrogel-injected animals both showed a similar response from ED1+ microglia and GFAP overexpression. No significant differences were found between saline-injected and hydrogel-injected groups for any of the measures studied, but there was a trend toward decreased affected area size from 1 to 2 weeks in both groups. Access to the central nervous system is limited by the blood–brain barrier for noninvasive therapies; further development of the current system for localized drug or cellular delivery has the potential to shape treatments of spinal cord injury.

Behavioral recovery from spinal cord injury following delayed application of polyethylene glycol

2002 ◽  
Vol 205 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Richard B. Borgens ◽  
Riyi Shi ◽  
Debra Bohnert
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Polyethylene Glycol ◽  
Guinea Pig ◽  
Topical Application ◽  
Spinal Cord Injuries ◽  
Thoracic Vertebrae ◽  
Behavioral Recovery ◽  
Thoracic Spinal Cord ◽  
Cord Injury

SUMMARY Topical application of the hydrophilic polymer polyethylene glycol (PEG) to isolated adult guinea pig spinal cord injuries has been shown to lead to the recovery of both the anatomical integrity of the tissue and the conduction of nerve impulses through the lesion. Furthermore, a brief (2 min) application of the fusogen (Mr 1800, 50 % w/v aqueous solution) to the exposed spinal cord injury in vivo can also cause rapid recovery of nerve impulse conduction through the lesion in association with functional recovery. Behavioral recovery was demonstrated using a long-tract, spinal-cord-dependent behavior in rodents known as the cutaneus trunci muscle (CTM) reflex. This reflex is observed as a contraction of the skin of the back in response to tactile stimulation. Here, we confirm and extend these preliminary observations. A severe compression/contusion injury to the exposed thoracic spinal cord of the guinea pig was performed between thoracic vertebrae 10 and 11. Approximately 7 h later, a topical application of PEG was made to the injury (dura removed) for 2 min in 15 experimental animals, and levels of recovery were compared with those of 13 vehicle-treated control animals. In PEG-treated animals, 93 % recovered variable levels of CTM functioning and all recovered some level of conduction through the lesion, as measured by evoked potential techniques. The recovered reflex was relatively normal compared with the quantitative characteristics of the reflex prior to injury with respect to the direction, distance and velocity of skin contraction. Only 23 % of the control population showed any spontaneous CTM recovery (P=0.0003) and none recovered conduction through the lesion during the 1 month period of observation (P=0.0001). These results suggest that repair of nerve membranes by polymeric sealing can provide a novel means for the rapid restoration of function following spinal cord injury.

scholarly journals A Sensitive and Fast Fiber Bragg Grating-Based Investigation of the Biomechanical Dynamics of In Vitro Spinal Cord Injuries

Sensors ◽  
2021 ◽  
Vol 21 (5) ◽  
pp. 1671
Author(s):  
Satyendra Kumar Mishra ◽  
Jean-Marc Mac-Thiong ◽  
Éric Wagnac ◽  
Yvan Petit ◽  
Bora Ung
Keyword(s):  
Spinal Cord ◽  
Fiber Bragg Grating ◽  
Real Time ◽  
Soft Tissues ◽  
Spinal Cord Injuries ◽  
Bragg Grating ◽  
Transverse Compression ◽  
Spatiotemporal Resolution ◽  
Cord Injury

To better understand the real-time biomechanics of soft tissues under sudden mechanical loads such as traumatic spinal cord injury (SCI), it is important to improve in vitro models. During a traumatic SCI, the spinal cord suffers high-velocity compression. The evaluation of spinal canal occlusion with a sensor is required in order to investigate the degree of spinal compression and the fast biomechanical processes involved. Unfortunately, available techniques suffer with drawbacks such as the inability to measure transverse compression and impractically large response times. In this work, an optical pressure sensing scheme based on a fiber Bragg grating and a narrow-band filter was designed to detect and demonstrate the transverse compression inside a spinal cord surrogate in real-time. The response time of the proposed scheme was 20 microseconds; a five orders of magnitude enhancement over comparable schemes that depend on costly and slower optical spectral analyzers. We further showed that this improvement in speed comes with a negligible loss in sensitivity. This study is another step towards better understanding the complex biomechanics involved during a traumatic SCI, using a method capable of probing the related internal strains with high-spatiotemporal resolution.

An In Situ Gelling Drug Delivery System for Improved Recovery after Spinal Cord Injury

2016 ◽  
Vol 5 (12) ◽  
pp. 1513-1521 ◽  
Author(s):  
Dongfei Liu ◽  
Tao Jiang ◽  
Weihua Cai ◽  
Jian Chen ◽  
Hongbo Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Drug Delivery System ◽  
Delivery System ◽  
Cord Injury ◽  
In Situ Gelling

scholarly journals Magnetic resonance imaging in lumbar gunshot wounds: an absolute contraindication?

2014 ◽  
Vol 37 (1) ◽  
pp. E13 ◽  
Author(s):  
Eduardo Martinez-del-Campo ◽  
Leonardo Rangel-Castilla ◽  
Hector Soriano-Baron ◽  
Nicholas Theodore
Keyword(s):  
Spinal Cord ◽  
Mr Imaging ◽  
Spinal Canal ◽  
English Language ◽  
Spinal Cord Injuries ◽  
Gunshot Wounds ◽  
Neurological Deficits ◽  
Neurological Improvement ◽  
Cord Injury

Object Performance of MR imaging in patients with gunshot wounds at or near the lumbar spinal canal is controversial. The authors reviewed the literature on the use of MR imaging in gunshot wounds to the spine. They discuss the results from in vitro and clinical studies, analyze the physical properties of common projectiles, and evaluate the safety and indications for MR imaging when metallic fragments are located near the spinal canal. Methods A review of the English-language literature was performed. Data from 25 articles were analyzed, including 5 in vitro studies of the interaction between 95 projectiles and the MR system's magnetic fields, and the clinical outcomes in 22 patients with metallic fragments at or near the spinal canal who underwent MR imaging. Results Properties of 95 civilian and military projectiles were analyzed at a magnet strength of 1, 1.5, 3, and 7 T. The most common projectiles were bullets with a core of lead, either with a copper jacket or unjacketed (73 [76.8%] of 95). Steel-containing (core or jacket) projectiles comprised 14.7%. No field interaction was evident in 78 (96.3%) of the 81 nonsteel projectiles. All steel projectiles showed at least positive deflection forces, longitudinal migration, or rotation. Heating of the projectiles was clinically insignificant. Image artifact was significant in all 9 steel bullets tested, but was not significant in 39 (88.6%) of the 44 nonsteel bullets tested. Overall, 22 patients with complete (82%) and incomplete (14%) spinal cord injury secondary to a projectile lodged inside the spinal canal underwent MR imaging. Discomfort and further physical or neurological deficits were not reported by any patient. Two patients with spinal cord injuries underwent MR imaging studies before surgical decompression and had subsequent, significant neurological improvement. Conclusions Metallic implants near or at the spinal canal are a relative contraindication for MR imaging. However, safe MR imaging might be feasible when a projectile's properties and a patient's individualized clinical presentation are considered.

scholarly journals Use of Autologous Mesenchymal Stem Cells Derived from Bone Marrow for the Treatment of Naturally Injured Spinal Cord in Dogs

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Euler Moraes Penha ◽  
Cássio Santana Meira ◽  
Elisalva Teixeira Guimarães ◽  
Marcus Vinícius Pinheiro Mendonça ◽  
Faye Alice Gravely ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Magnetic Resonance ◽  
Spinal Cord Injuries ◽  
Autologous Bone Marrow ◽  
Therapeutic Effects ◽  
Cord Injury

The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were culturedin vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury.

scholarly journals Wild Bitter Melon Exerts Anti-Inflammatory Effects by Upregulating Injury-Attenuated CISD2 Expression following Spinal Cord Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Woon-Man Kung ◽  
Chai-Ching Lin ◽  
Chan-Yen Kuo ◽  
Yu-Ching Juin ◽  
Po-Ching Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Signaling Pathway ◽  
Spinal Cord Injuries ◽  
Inflammatory Responses ◽  
Peroxisome Proliferator ◽  
Neural Cells ◽  
Bitter Melon ◽  
Cord Injury ◽  
Anti Inflammatory

Background. Spinal cord injuries (SCIs) induce secondary neuroinflammation through astrocyte reactivation, which adversely affects neuronal survival and eventually causes long-term disability. CDGSH iron sulfur domain 2 (CISD2), which has been reported to be involved in mediating the anti-inflammatory responses, can serve as a target in SCI therapy. Wild bitter melon (WBM; Momordica charantia Linn. var. abbreviata Ser.) contains an anti-inflammatory agent called alpha-eleostearic acid (α-ESA), a peroxisome proliferator-activated receptor-β (PPAR-β) ligand. Activated PPAR-β inhibits the nuclear factor κB (NF-κB) signaling pathway via the inhibition of IκB (inhibitor of NF-κB) degradation. The role of astrocyte deactivation and CISD2 in anti-inflammatory mechanisms of WBM in acute SCIs is unknown. Materials and Methods. A mouse model of SCI was generated via spinal cord hemisection. The SCI mice were administered WBM intraperitoneally (500 mg/kg bodyweight). Lipopolysaccharide- (LPS-) stimulated ALT cells (astrocytes) were used as an in vitro model for studying astrocyte-mediated inflammation post-SCI. The roles of CISD2 and PPAR-β in inflammatory signaling were examined using LPS-stimulated SH-SY5Y cells transfected with si-CISD2 or scramble RNA. Results. WBM mitigated the SCI-induced downregulation of CISD2, PPAR-β, and IκB and upregulation of glial fibrillary acidic protein (GFAP; marker of astrocyte reactivation) in the spinal cord of SCI mice. Additionally, WBM (1 μg/mL) mitigated LPS-induced CISD2 downregulation. Furthermore, SH-SY5Y neural cells with CISD2 knockdown exhibited decreased PPAR-β expression and augmented NF-κB signaling. Conclusion. To the best of our knowledge, this is the first study to report that CISD2 is an upstream modulator of the PPAR-β/NF-κB proinflammatory signaling pathway in neural cells, and that WBM can mitigate the injury-induced downregulation of CISD2 in SCI mice and LPS-stimulated ALT astrocytes.

In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury

Biomaterials ◽  
2006 ◽  
Vol 27 (3) ◽  
pp. 497-504 ◽  
Author(s):  
Anjana Jain ◽  
Young-Tae Kim ◽  
Robert J. McKeon ◽  
Ravi V. Bellamkonda
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Local Delivery ◽  
Cord Injury ◽  
In Situ Gelling

Impairment Rating and Spinal Cord Injuries: Revisiting the Guides

2010 ◽  
Vol 15 (3) ◽  
pp. 1-7
Author(s):  
Richard T. Katz
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Functional Independence ◽  
Outcome Data ◽  
Multiple Organ ◽  
Loss Of Function ◽  
Sixth Edition ◽  
Organ Systems ◽  
Cord Injury ◽  
Impairment Ratings

Abstract This article addresses some criticisms of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) by comparing previously published outcome data from a group of complete spinal cord injury (SCI) persons with impairment ratings for a corresponding level of injury calculated using the AMA Guides, Sixth Edition. Results of the comparison show that impairment ratings using the sixth edition scale poorly with the level of impairments of activities of daily living (ADL) in SCI patients as assessed by the Functional Independence Measure (FIM) motor scale and the extended FIM motor scale. Because of the combinations of multiple impairments, the AMA Guides potentially overrates the impairment of paraplegics compared with that of quadriplegics. The use and applicability of the Combined Values formula should be further investigated, and complete loss of function of two upper extremities seems consistent with levels of quadriplegia using the SCI model. Some aspects of the AMA Guides contain inconsistencies. The concept of diminishing impairment values is not easily translated between specific losses of function per organ system and “overall” loss of ADLs involving multiple organ systems, and the notion of “catastrophic thresholds” involving multiple organ systems may support the understanding that variations in rating may exist in higher rating cases such as those that involve an SCI.

scholarly journals Dietary Supplementation for Para-Athletes: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2016
Author(s):  
Keely A. Shaw ◽  
Gordon A. Zello ◽  
Brian Bandy ◽  
Jongbum Ko ◽  
Leandy Bertrand ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dietary Supplements ◽  
Sports Medicine ◽  
Spinal Cord Injuries ◽  
Sport Performance ◽  
Future Research ◽  
Inclusion Criteria ◽  
Supplement Use ◽  
Sport Supplements ◽  
Cord Injury

The use of dietary supplements is high among athletes and non-athletes alike, as well as able-bodied individuals and those with impairments. However, evidence is lacking in the use of dietary supplements for sport performance in a para-athlete population (e.g., those training for the Paralympics or similar competition). Our objective was to examine the literature regarding evidence for various sport supplements in a para-athlete population. A comprehensive literature search was conducted using PubMed, SPORTDiscus, MedLine, and Rehabilitation and Sports Medicine Source. Fifteen studies met our inclusion criteria and were included in our review. Seven varieties of supplements were investigated in the studies reviewed, including caffeine, creatine, buffering agents, fish oil, leucine, and vitamin D. The evidence for each of these supplements remains inconclusive, with varying results between studies. Limitations of research in this area include the heterogeneity of the subjects within the population regarding functionality and impairment. Very few studies included individuals with impairments other than spinal cord injury. Overall, more research is needed to strengthen the evidence for or against supplement use in para-athletes. Future research is also recommended on performance in para-athlete populations with classifiable impairments other than spinal cord injuries.

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