The Effect of Flash Freezing on Variability in Spinal Cord Compression Behavior

The compression behavior of spinal cord tissue is important for understanding spinal cord injury mechanics but has not yet been established. Characterizing compression behavior assumes precise specimen geometry; however, preparing test specimens of spinal cord tissue is complicated by the extreme compliance of the tissue. The objectives of this study were to determine the effect of flash freezing on both specimen preparation and mechanical response and to quantify the effect of small deviations in specimen geometry on mechanical behavior. Specimens of porcine spinal cord white matter were harvested immediately following sacrifice. The tissue was divided into two groups: partially frozen specimens were flash frozen (60 s at −80°C) prior to cutting, while fresh specimens were kept at room temperature. Specimens were tested in unconfined compression at strain rates of 0.05 s−1 and 5.0 s−1 to 40% strain. Parametric finite element analyses were used to investigate the effect of specimen face angle, cross section, and interface friction on the mechanical response. Flash freezing did not affect the mean mechanical behavior of the tissue but did reduce the variability in the response across specimens (p<0.05). Freezing also reduced variability in the specimen geometry. Variations in specimen face angle (0–10 deg) resulted in a 34% coefficient of variation and a 60% underestimation of peak stress. The effect of geometry on variation and error was greater than that of interface friction. Taken together, these findings demonstrate the advantages of flash freezing in biomechanical studies of spine cord tissue.

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Spinal Cord Repair: From Cells and Tissue Engineering to Extracellular Vesicles

Cells ◽

10.3390/cells10081872 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1872

Author(s):

Shaowei Guo ◽

Idan Redenski ◽

Shulamit Levenberg

Keyword(s):

Spinal Cord ◽

Tissue Engineering ◽

Extracellular Vesicles ◽

Functional Recovery ◽

Three Dimensional ◽

Therapeutic Modality ◽

Spinal Cord Tissue ◽

New Paradigm ◽

Cord Injury ◽

Severe Motor

Spinal cord injury (SCI) is a debilitating condition, often leading to severe motor, sensory, or autonomic nervous dysfunction. As the holy grail of regenerative medicine, promoting spinal cord tissue regeneration and functional recovery are the fundamental goals. Yet, effective regeneration of injured spinal cord tissues and promotion of functional recovery remain unmet clinical challenges, largely due to the complex pathophysiology of the condition. The transplantation of various cells, either alone or in combination with three-dimensional matrices, has been intensively investigated in preclinical SCI models and clinical trials, holding translational promise. More recently, a new paradigm shift has emerged from cell therapy towards extracellular vesicles as an exciting “cell-free” therapeutic modality. The current review recapitulates recent advances, challenges, and future perspectives of cell-based spinal cord tissue engineering and regeneration strategies.

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The Role of IL-17 Promotes Spinal Cord Neuroinflammation via Activation of the Transcription Factor STAT3 after Spinal Cord Injury in the Rat

Mediators of Inflammation ◽

10.1155/2014/786947 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 24

Author(s):

Shaohui Zong ◽

Gaofeng Zeng ◽

Ye Fang ◽

Jinzhen Peng ◽

Yong Tao ◽

...

Keyword(s):

Spinal Cord ◽

Hind Limb ◽

Rating Scale ◽

Serum Levels ◽

Spinal Cord Tissue ◽

Expression Levels ◽

Stat3 Signaling ◽

Cord Injury ◽

Disease Stages

Study Design.In this study, we investigated the role of IL-17 via activation of STAT3 in the pathophysiology of SCI.Objective.The purpose of the experiments is to study the expression of IL-17 and related cytokines via STAT3 signaling pathways, which is caused by the acute inflammatory response following SCI in different periods via establishing an acute SCI model in rat.Methods.Basso, Beattie, and Bresnahan hind limb locomotor rating scale was used to assess the rat hind limb motor function. Immunohistochemistry was used to determine the expression levels of IL-17 and p-STAT3 in spinal cord tissues. Western blotting analysis was used to determine the protein expression of p-STAT3 in spinal cord tissue. RT-PCR was used to analyze the mRNA expression of IL-17 and IL-23p19 in the spleen tissue. ELISA was used to determine the peripheral blood serum levels of IL-6, IL-21, and IL-23.Results.Compared to the sham-operated group, the expression levels of IL-17, p-STAT3, IL-6, IL-21, and IL-23 were significantly increased and peaked at 24 h after SCI. The increased levels of cytokines were correlated with the SCI disease stages.Conclusion.IL-17 may play an important role in promoting spinal cord neuroinflammation after SCI via activation of STAT3.

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Spinal Cord Tissue Bridges Validation Study: Predictive Relationships With Sensory Scores Following Cervical Spinal Cord Injury

Topics in Spinal Cord Injury Rehabilitation ◽

10.46292/sci21-00018 ◽

2021 ◽

Author(s):

Andrew C. Smith ◽

Denise R. O’Dell ◽

Wesley A. Thornton ◽

David Dungan ◽

Eli Robinson ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

External Validation ◽

Inpatient Rehabilitation ◽

Spinal Cord Tissue ◽

Light Touch ◽

Post Injury ◽

Data Set ◽

Cord Injury ◽

Predictive Relationships

Background: Using magnetic resonance imaging (MRI), widths of ventral tissue bridges demonstrated significant predictive relationships with future pinprick sensory scores, and widths of dorsal tissue bridges demonstrated significant predictive relationships with future light touch sensory scores, following spinal cord injury (SCI). These studies involved smaller participant numbers, and external validation of their findings is warranted. Objectives: The purpose of this study was to validate these previous findings using a larger independent data set. Methods: Widths of ventral and dorsal tissue bridges were quantified using MRI in persons post cervical level SCI (average 3.7 weeks post injury), and pinprick and light touch sensory scores were acquired at discharge from inpatient rehabilitation (average 14.3 weeks post injury). Pearson product-moments were calculated and linear regression models were created from these data. Results: Wider ventral tissue bridges were significantly correlated with pinprick scores (r = 0.31, p < 0.001, N = 136) and wider dorsal tissue bridges were significantly correlated with light touch scores (r = 0.31, p < 0.001, N = 136) at discharge from inpatient rehabilitation. Conclusion: This retrospective study’s results provide external validation of previous findings, using a larger sample size. Following SCI, ventral tissue bridges hold significant predictive relationships with future pinprick sensory scores and dorsal tissue bridges hold significant predictive relationships with future light touch sensory scores.

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Mechanisms leading to restoration of muscle size with exercise and transplantation after spinal cord injury

AJP Cell Physiology ◽

10.1152/ajpcell.2000.279.6.c1677 ◽

2000 ◽

Vol 279 (6) ◽

pp. C1677-C1684 ◽

Cited By ~ 59

Author(s):

Esther E. Dupont-Versteegden ◽

René J. L. Murphy ◽

John D. Houlé ◽

Cathy M. Gurley ◽

Charlotte A. Peterson

Keyword(s):

Spinal Cord ◽

Satellite Cell ◽

Fiber Type ◽

Cell Activity ◽

Muscle Size ◽

Spinal Cord Tissue ◽

Cellular Mechanisms ◽

Cross Sectional ◽

Cord Injury ◽

Nuclear Number

We have shown that cycling exercise combined with fetal spinal cord transplantation restored muscle mass reduced as a result of complete transection of the spinal cord. In this study, mechanisms whereby this combined intervention increased the size of atrophied soleus and plantaris muscles were investigated. Rats were divided into five groups ( n = 4, per group): control, nontransected; spinal cord transected at T10 for 8 wk (Tx); spinal cord transected for 8 wk and exercised for the last 4 wk (TxEx); spinal cord transected for 8 wk with transplantation of fetal spinal cord tissue into the lesion site 4 wk prior to death (TxTp); and spinal cord transected for 8 wk, exercised for the last 4 wk combined with transplantation 4 wk prior to death (TxExTp). Tx soleus and plantaris muscles were decreased in size compared with control. Exercise and transplantation alone did not restore muscle size in soleus, but exercise alone minimized atrophy in plantaris. However, the combination of exercise and transplantation resulted in a significant increase in muscle size in soleus and plantaris compared with transection alone. Furthermore, myofiber nuclear number of soleus was decreased by 40% in Tx and was not affected in TxEx or TxTp but was restored in TxExTp. A strong correlation ( r = 0.85) between myofiber cross-sectional area and myofiber nuclear number was observed in soleus, but not in plantaris muscle, in which myonuclear number did not change with any of the experimental manipulations. 5′-Bromo-2′-deoxyuridine-positive nuclei inside the myofiber membrane were observed in TxExTp soleus muscles, indicating that satellite cells had divided and subsequently fused into myofibers, contributing to the increase in myonuclear number. The increase in satellite cell activity did not appear to be controlled by the insulin-like growth factors (IGF), as IGF-I and IGF-II mRNA abundance was decreased in Tx soleus and plantaris, and was not restored with the interventions. These results indicate that, following a relatively long postinjury interval, exercise and transplantation combined restore muscle size. Satellite cell fusion and restoration of myofiber nuclear number contributed to increased muscle size in the soleus, but not in plantaris, suggesting that cellular mechanisms regulating muscle size differ between muscles with different fiber type composition.

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METHODS OF PHYSIOTHERAPY FOR STUDY IN A SPINAL INSULT

Knowledge International Journal ◽

10.35120/kij29082565d ◽

2018 ◽

Vol 28 (7) ◽

pp. 2565-2566

Author(s):

Daniela Popova ◽

Mariela Filipova

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Back Pain ◽

Young People ◽

Hemorrhagic Stroke ◽

Muscle Spasm ◽

Spinal Cord Tissue ◽

Blood Diseases ◽

Cord Injury ◽

Ischemic Spinal Cord Injury

Spinal stroke is a disease that is rare in neurological practice. Affects young people, mostly at the age of 30 years [2]. It may be ischemic or haemorrhagic. Etiological, ischemic spinal stroke is caused by atherosclerosis of the aorta and blood vessels of the spinal cord, muscle spasm, vasculitis, pregnancy, hemangioma or hernia [3, 4]. Hemorrhagic stroke is caused by dysplasia, tumors and blood diseases involving increased bleeding [1]. Spinal infarction most commonly develops in the basal spinal artery pool, which is responsible for the blood supply of the anterior 2/3 of the spinal cord tissue. Often, the disease starts with a sudden back pain with an enigmatic nature (in the area of the thoracic segment - Th 8), a gradually occurring weakness in the limbs and hypestesia, pelvic-tangle disorders [5]. The gait is very difficult to impossible.Purpose of the study: To test neurological tests in patients with spinal ischemic spinal cord injury. Assess their accessibility and reliability.

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Genistein Loaded Nanofibers Protect Spinal Cord Tissue Following Experimental Injury in Rats

10.20944/preprints201809.0424.v1 ◽

2018 ◽

Author(s):

Mohamed Ismail ◽

Sara Ibrahim ◽

Azza Elamir ◽

Amira M. Elrafei ◽

Nageh Allam ◽

...

Keyword(s):

Drug Delivery ◽

Spinal Cord ◽

Drug Delivery System ◽

Delivery System ◽

Enhanced Recovery ◽

Therapeutic Drug ◽

Control Group ◽

Spinal Cord Tissue ◽

Injured Spinal Cord ◽

Cord Injury

Implantable drug-delivery systems provide new means for achieving therapeutic drug concentration over a prolonged time to achieve better tissue protection and enhanced recovery. The hypothesis of the current study was to test the antioxidant and anti-inflammatory effects of genistein and nanofibers on the spinal cord tissue following experimental spinal cord injury (SCI). Rats were treated post SCI with genistein loaded on chitosan/polyvinyl alcohol (CS/PVA) nanofibers as an implantable drug-delivery system. SCI caused marked oxidative damage and inflammation as evident by the reduction in the super oxide dismutase (SOD) activity and the level of interleukin-10 (IL-10) in injured spinal cord tissue, as well as, the significant increase in the levels of nitric oxide (NO), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α). Treatment of rats post SCI with genistein and CS/PVA nanofibers improved most of the above mentioned biochemical parameters and shifted them toward the control group values. Genistein induced an increase in the activity of SOD and the level of IL-10, while causing a decrease in the levels of NO, MDA and TNF-α in injured spinal cord tissue. Genistein and CS/PVA nanofibers provide a novel combination for treating inflammatory nervous tissue conditions, especially when combined as an implantable drug-delivery system.

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Inhibition of x-irradiation–enhanced locomotor recovery after spinal cord injury by hyperbaric oxygen or the antioxidant nitroxide tempol

Journal of Neurosurgery Spine ◽

10.3171/spi.2007.6.4.9 ◽

2007 ◽

Vol 6 (4) ◽

pp. 337-343 ◽

Cited By ~ 7

Author(s):

Virany H. Hillard ◽

Hong Peng ◽

Kaushik Das ◽

Raj Murali ◽

Chitti R. Moorthy ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Hyperbaric Oxygen ◽

Spinal Cord Tissue ◽

Irradiation Site ◽

Injury Site ◽

Locomotor Recovery ◽

Locomotor Function ◽

Cord Injury ◽

X Irradiation

Object Hyperbaric oxygen (HBO), the nitroxide antioxidant tempol, and x-irradiation have been used to promote locomotor recovery in experimental models of spinal cord injury. The authors used x-irradiation of the injury site together with either HBO or tempol to determine whether combined therapy offers greater benefit to rats. Methods Contusion injury was produced with a weight-drop device in rats at the T-10 level, and recovery was determined using the 21-point Basso-Beattie-Bresnahan (BBB) locomotor scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater after x-irradiation (20 Gy) of the injury site or treatment with tempol (275 mg/kg intraperitoneally) than in untreated rats (final BBB Scores 10.6 [x-irradiation treated] and 9.1 [tempol treated] compared with 6.4 [untreated], p < 0.05). Recovery was not significantly improved by HBO (2 atm for 1 hour [BBB Score 8.2, p > 0.05]). Interestingly, the improved recovery of locomotor function after x-irradiation, in contrast with antiproliferative radiotherapy for neoplasia, was inhibited when used together with either HBO or tempol (BBB Scores 8.2 and 8.3, respectively). The ability of tempol to block enhanced locomotor recovery by x-irradiation was accompanied by prevention of alopecia at the irradiation site. The extent of locomotor recovery following treatment with tempol, HBO, and x-irradiation correlated with measurements of spared spinal cord tissue at the contusion epicenter. Conclusions These results suggest that these treatments, when used alone, can activate neuroprotective mechanisms but, in combination, may result in neurotoxicity.

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Resveratrol on the Inflammatory Environment of Rat Bone Marrow Mesenchymal Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2749 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1932-1939

Author(s):

Shaofeng Tang ◽

Nvzhao Yao ◽

Dahai Qin

Keyword(s):

Spinal Cord ◽

Sham Group ◽

Inflammatory Factors ◽

Sham Operation ◽

Spinal Cord Tissue ◽

Sham Operation Group ◽

Western Blot Method ◽

Cord Injury ◽

Operation Group ◽

Bone Marrow Mesenchymal Cells

Our study assesses the mechanism of Sirt-1 signaling pathway and inflammation changes after spinal cord injury (SCI). SD rats were assigned into Sham group and SCI group. The Sham group only received bites off the corresponding vertebral lamina without the blow operation. The Western Blot method was used to detect Sirt-1 level, ELISA analyzed IL-1β and IL-6 level in the spinal cord tissues along with measuring Sirt-1 and TNF-α level by immunofluorescence staining. Sirt-1 changed with the time after SCI and was significantly higher than sham operation group at 1 day after injury, reaching the highest level at 3 days followed by a decrease. IL-1β and IL-6 after SCI was significantly higher than sham operation group at 1 day after injury. Immunofluorescence double staining showed that Sirt-1 and TNF-α expression in spinal cord tissue after injury were upregulated. The expression of Sirt-1 changed with time after SCI, and was consistent with the trend of changes in inflammatory factors. In conclusion, Sirt-1 is related to the changes of inflammatory factors after SCI, indicating that Sirt-1 may be involved in inflammation after SCI.

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Numbers of Axons in Spared Neural Tissue Bridges But Not Their Widths or Areas Correlate With Functional Recovery in Spinal Cord-Injured Rats

Journal of Neuropathology & Experimental Neurology ◽

10.1093/jnen/nlaa050 ◽

2020 ◽

Vol 79 (11) ◽

pp. 1203-1217

Author(s):

Svenja Rink ◽

Stoyan Pavlov ◽

Aliona Wöhler ◽

Habib Bendella ◽

Marilena Manthou ◽

...

Keyword(s):

Spinal Cord ◽

Functional Recovery ◽

Neural Tissue ◽

Cord Compression ◽

Cresyl Violet ◽

Spinal Cord Tissue ◽

Class Iii ◽

Morphological Findings ◽

Cord Injury ◽

Magnetic Resonance Imaging Mri

Abstract The relationships between various parameters of tissue damage and subsequent functional recovery after spinal cord injury (SCI) are not well understood. Patients may regain micturition control and walking despite large postinjury medullar cavities. The objective of this study was to establish possible correlations between morphological findings and degree of functional recovery after spinal cord compression at vertebra Th8 in rats. Recovery of motor (Basso, Beattie, Bresnahan, foot-stepping angle, rump-height index, and ladder climbing), sensory (withdrawal latency), and bladder functions was analyzed at 1, 3, 6, 9, and 12 weeks post-SCI. Following perfusion fixation, spinal cord tissue encompassing the injury site was cut in longitudinal frontal sections. Lesion lengths, lesion volumes, and areas of perilesional neural tissue bridges were determined after staining with cresyl violet. The numbers of axons in these bridges were quantified after staining for class III β-tubulin. We found that it was not the area of the spared tissue bridges, which is routinely determined by magnetic resonance imaging (MRI), but the numbers of axons in them that correlated with functional recovery after SCI (Spearman’s ρ > 0.8; p < 0.001). We conclude that prognostic statements based only on MRI measurements should be considered with caution.

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Cerebrospinal fluid lactate and electrolyte levels following experimental spinal cord injury

Journal of Neurosurgery ◽

10.3171/jns.1976.44.6.0715 ◽

1976 ◽

Vol 44 (6) ◽

pp. 715-722 ◽

Cited By ~ 50

Author(s):

Douglas K. Anderson ◽

Leon D. Prockop ◽

Eugene D. Means ◽

Lawrence E. Hartley

Keyword(s):

Spinal Cord ◽

Cerebrospinal Fluid ◽

Spinal Cord Compression ◽

Cord Compression ◽

Spinal Cord Tissue ◽

Post Injury ◽

Content Type ◽

Protein Levels ◽

Cord Injury ◽

Csf Lactate

✓ Cerebrospinal fluid (CSF) lactate, sodium (Na+), potassium (K+), calcium (Ca++), magnesium (Mg++), and chloride (Cl−) levels were determined for 17 to 21 days following experimental spinal cord compression in cats. Laminectomies were performed at L-2 under general anesthesia with aseptic techniques. Paraplegia was produced by applying a 170-gm weight transdurally for 5 minutes. Significant increases in CSF lactate levels were observed on the first through ninth days post injury with peak levels (50% above normal) occurring at Day 5. The only significant postinjury CSF electrolyte changes were elevation in Ca++ concentration on Days 3, 9, 11, 13, and 15, elevation in K+ concentration on Days 9 and 11 and decline in Cl− levels on the first day. The CSF K+ increase probably reflected cellular loss of K+ from damaged tissue whereas the Ca++ rise may have resulted from increased CSF protein levels. The prolonged elevation of CSF lactate indicates that tissue hypoxia plays a role in spinal cord compression paralysis, and that there is a continuing hypoxia of metabolically active spinal cord tissue for several days post injury.

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