How to generate graded spinal cord injuries in swine - tools and procedures.
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ABSTRACT:
SUBMITTER: Zuchner M
PROVIDER: S-EPMC8419714 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Spinal cord injury (SCI) is a highly debilitating neurological disease, which still lacks effective treatment strategies, causing significant financial burden and distress to the affected families. Nevertheless, nanotechnology and regenerative medicine strategies holding promise for the development of novel therapies that would reach from bench to bedside to serve the SCI patients. There has already been significant progress in the field of cell-based therapies, with the clinical application for SCI, currently in phase II of the clinical trial. Stem cells (e.g., induced pluripotent stem cells, fetal stem cells, human embryonic stem cells, and olfactory ensheathing cells) are certainly not to be considered the panacea for neural repair but, especially when combined with rehabilitation or other combinatorial approaches using the help of nanotechnology, they seem to be the source of some of the most promising and clinical translatable cell-based therapies that could help solving impactful problems on neural repair.
| S-EPMC5840986 | biostudies-literature
Project description:Methylprednisolone sodium succinate (MPSS) for treatment of acute spinal cord injury (SCI) has been associated with both benefits and adverse events. MPSS administration was the standard of care for acute SCI until recently when its use has become controversial. Patients with SCI have had little input in the debate, thus we sought to learn their opinions regarding administration of MPSS. A summary of the published literature to date on MPSS use for acute SCI was created and adjudicated by 28 SCI experts. This summary was then emailed to 384 chronic SCI patients along with a survey that interrogated the patients' neurological deficits, communication with physicians and their views on MPSS administration. 77 out of 384 patients completed the survey. 28 respondents indicated being able to speak early after injury and of these 24 reported arriving at the hospital within 8 hours of injury. One recalled a physician speaking to them about MPSS and one patient reported choosing whether or not to receive MPSS. 59.4% felt that the small neurological benefits associated with MPSS were 'very important' to them (p<0.0001). Patients had 'little concern' for potential side-effects of MPSS (p = 0.001). Only 1.4% felt that MPSS should not be given to SCI patients regardless of degree of injury (p<0.0001). This is the first study to report SCI patients' preferences regarding MPSS treatment for acute SCI. Patients favor the administration of MPSS for acute SCI, however few had input into whether or not it was administered. Conscious patients should be given greater opportunity to decide their treatment. These results also provide some guidance regarding MPSS administration in patients unable to communicate.
| S-EPMC4720442 | biostudies-literature
Project description:A bioengineered spinal cord is fabricated via extrusion-based multi-material 3D bioprinting, in which clusters of induced pluripotent stem cell (iPSC)-derived spinal neuronal progenitor cells (sNPCs) and oligodendrocyte progenitor cells (OPCs) are placed in precise positions within 3D printed biocompatible scaffolds during assembly. The location of a cluster of cells, of a single type or multiple types, is controlled using a point-dispensing printing method with a 200 μm center-to-center spacing within 150 μm wide channels. The bioprinted sNPCs differentiate and extend axons throughout microscale scaffold channels, and the activity of these neuronal networks is confirmed by physiological spontaneous calcium flux studies. Successful bioprinting of OPCs in combination with sNPCs demonstrates a multicellular neural tissue engineering approach, where the ability to direct the patterning and combination of transplanted neuronal and glial cells can be beneficial in rebuilding functional axonal connections across areas of central nervous system (CNS) tissue damage. This platform can be used to prepare novel biomimetic, hydrogel-based scaffolds modeling complex CNS tissue architecture in vitro and harnessed to develop new clinical approaches to treat neurological diseases, including spinal cord injury.
| S-EPMC7319181 | biostudies-literature
Project description:The environment within the spinal cord after injury, which changes in the progression from the acute to chronic stages, limits the extent of regeneration. The delivery of inductive factors to promote regeneration following spinal cord injury has been promising, yet, few strategies are versatile to allow delivery during acute or chronic injury that would facilitate screening of candidate therapies. This report investigates the intrathecal delivery of lentiviruses for long-term expression of regenerative factors. Lentivirus-filled sponges were inserted into the intrathecal space surrounding the spinal cord, with transgene expression observed within multiple cell types that persists for 12 weeks for both intact and injured spinal cord, without any apparent damage to the spinal cord tissue. Sponges loaded with lentivirus encoding for Sonic hedgehog (Shh) were investigated for acute (delivered at 0 weeks) and chronic (at 4 weeks) injuries, and for multiple locations relative to the injury. In an acute model, sponges placed directly above the injury increased oligodendrocyte and decreased astrocyte presence. Sponges placed caudal to the injury had reduced impact on oligodendrocytes and astrocytes in the injury. In a chronic model, sponges increased oligodendrocyte and decreased astrocyte presence. Furthermore, the effect of Shh was shown to be mediated in part by reduction of Bmp signaling, monitored with an Msx2-sensitive reporter vector. The implantation of lentivirus-loaded biomaterials intrathecally provides the opportunity to induce the expression of a factor at a specified time without entering the spinal cord, and has the potential to promote gene delivery within the spinal cord, which can influence the extent of regeneration.
| S-EPMC4385414 | biostudies-literature
Project description:ObjectiveDescribe perceptions of persons with SCI on their receipt of holistic care and relational empathy during health care encounters.DesignMailed survey.Participants/settingIndividuals with SCI who received care from the largest suppliers of SCI care and rehabilitation (Veterans Health Administration and SCI Model Systems).Outcome measuresUsing a survey and administrative databases, we collected demographic and injury characteristics, health status, health conditions, and the main outcome: Consultation and Relational Empathy (CARE) measure.ResultsThe sample included 450 individuals with SCI (124 Veterans and 326 civilians). Response rate was 39% (450/1160). Analyses were conducted on patients with complete data (n = 389). Veterans and civilians with SCI differed across many demographic characteristics, age at injury, and etiology, but mean CARE scores were equivalent. Fewer than half of the full SCI cohort had CARE scores above the normative value of 43. Having a recent pressure ulcer showed a trend for lower odds of having a normative or higher CARE score. Odds of having an above-normative CARE score were nearly 2 times greater for individuals with tetraplegia, and odds were higher for those with higher physical and mental health status.ConclusionsHigher physical and mental health status and tetraplegia were each independently associated with greater perceptions of holistic care and empathy in the therapeutic patient-provider relationship. Limited empathy, communication, and holistic care may arise when providers focus on disease/disease management, rather than on patients as individuals. Frequent health care use and secondary conditions may affect empathy and holistic care in encounters, making it essential to understand and employ efforts to improve the therapeutic relationship between patients with SCI and their providers.
| S-EPMC5376142 | biostudies-literature
Project description:BackgroundCombined injuries to the spinal cord and brachial plexus present challenges in the detection of both injuries as well as to subsequent treatment. The purpose of this study is to describe the epidemiology and clinical factors of concomitant spinal cord injuries in patients with a known brachial plexus injury.MethodsA retrospective review was performed on all patients who were evaluated for a brachial plexus injury in a tertiary, multidisciplinary brachial plexus clinic from January 2000 to December 2008. Patients with clinical and/or imaging findings for a coexistent spinal cord injury were identified and underwent further analysis.ResultsA total of 255 adult patients were evaluated for a traumatic traction injury to the brachial plexus. We identified thirty-one patients with a combined brachial plexus and spinal cord injury, for a prevalence of 12.2%. A preganglionic brachial plexus injury had been sustained in all cases. The combined injury group had a statistically greater likelihood of having a supraclavicular vascular injury (odds ratio [OR] = 22.5; 95% confidence interval [CI] = 1.9, 271.9) and a cervical spine fracture (OR = 3.44; 95% CI = 1.6, 7.5). These patients were also more likely to exhibit a Horner sign (OR = 3.2; 95% CI = 1.5, 7.2) and phrenic nerve dysfunction (OR = 2.5; 95% CI = 1.0, 5.8) compared with the group with only a brachial plexus injury.ConclusionHeightened awareness for a combined spinal cord and brachial plexus injury and the presence of various associated clinical and imaging findings may aid in the early recognition of these relatively uncommon injuries.
| S-EPMC3234346 | biostudies-literature
Project description:Study designAcute experimental study.ObjectivesCold-induced vasodilation is a local mechanism of protection against frostbite in non-injured persons. We assessed whether an increase in skin blood flow (SkBF) during local cooling (LC) was observed in individuals with spinal cord injuries (SCIs) and if the response patterns differed between region levels or sites.SettingLaboratory of Wakayama Medical University and the affiliated clinics, Japan.MethodsA local cooler device (diameter 4 cm) was placed on the chest (sensate) and right thigh (non-sensate) in persons with cervical (SCIC; n = 9) and thoracolumbar SCIs (SCITL; n = 9). After the surface temperature under the device was controlled at 33 °C for 10 min (baseline), LC (-0.045 °C/s) was applied and the skin temperature was maintained at 15 and 8 °C for 15 min of each stage. SkBF (laser Doppler flowmetry) was monitored using a 1-mm needle-type probe inserted into its center.ResultsThe percent change in SkBF (%ΔSkBF) on the chest remained unchanged until the end of 15 °C stage; thereafter, it increased to a level at least 70% greater than the baseline during the 8 °C stage in both groups. The %ΔSkBF on the thigh in both SCIC and SCITL notably increased from 8 and 6 min respectively, during the 8°C stage, compared to 1 min before the stage; however, it did not exceed the baseline level.ConclusionsAn increase in SkBF during LC was observed both in the sensate and non-sensate areas in SCIs, although the magnitude was larger in the sensate area.
| S-EPMC11003866 | biostudies-literature
Project description:BackgroundGiven the indispensable role of animal models in preclinical studies of spinal cord injury (SCI) and the current state of available impactors, we designed a modified impactor for establishing contusion SCI in rats. The major improvement is the replacement of the impactor rod with a weight and an impactor tip.MethodsPreoperatively, radiographs of 8-week-old female Wistar rats were taken to establish a protocol for locating the target spinal segment. A total of 72 rats were randomly divided into 4 groups: the sham, 12.5-, 25- and 50-mm groups. Within 35 days postinjury (dpi), the Basso, Beattie, and Bresnahan locomotor rating scale (BBB) was used to evaluate the hindlimb motor function of the rats. At 7 dpi, the rats were sacrificed, and the spinal cord tissue was fixed. Hematoxylin-eosin (HE) staining was used to assess histological changes. Subsequently, immunofluorescence staining was performed to visualize the expression and distribution of GFAP, CD68, MBP, and NeuN. Additionally, rats were sacrificed, and their tissues were extracted for relevant protein assays. At 3 and 7 dpi, electrophysiological function was evaluated by measuring motor evoked potentials (MEPs) and sensory evoked potentials (SEPs).ResultsThe behavioral results revealed that higher strike heights were associated with lower BBB scores. Over time, the BBB scores of the SCI rats exhibited an improving trend. Quantitative analysis of the lesions indicated that as the impact height increased, the area of histological destruction, GFAP-negative area, CD68-positive cell count, and MBP-positive destruction area increased, and the number of NeuN-positive cells decreased. Western blot analysis further verified relevant protein changes. Electrophysiology confirmed that the MEP and SEP amplitudes decreased as the strike height increased.ConclusionsThus, these results confirm that this modified impactor can be used to establish a graded SCI model in rats. The model is clinically relevant, reproducible, stable, accessible, and affordable, providing a practical tool with which to elucidate the pathophysiological mechanisms and potential therapies for contusive SCI.
| S-EPMC9096392 | biostudies-literature
Project description:BackgroundAcute, severe traumatic spinal cord injury often causes fecal incontinence. Currently, there are no treatments to improve anal function after traumatic spinal cord injury. Our study aims to determine whether, after traumatic spinal cord injury, anal function can be improved by interventions in the neuro-intensive care unit to alter the spinal cord perfusion pressure at the injury site.MethodsWe recruited a cohort of patients with acute, severe traumatic spinal cord injuries (American Spinal Injury Association Impairment Scale grades A-C). They underwent surgical fixation within 72 h of the injury and insertion of an intrathecal pressure probe at the injury site to monitor intraspinal pressure and compute spinal cord perfusion pressure as mean arterial pressure minus intraspinal pressure. Injury-site monitoring was performed at the neuro-intensive care unit for up to a week after injury. During monitoring, anorectal manometry was also conducted over a range of spinal cord perfusion pressures.ResultsData were collected from 14 patients with consecutive traumatic spinal cord injury aged 22-67 years. The mean resting anal pressure was 44 cmH2O, which is considerably lower than the average for healthy patients, previously reported at 99 cmH2O. Mean resting anal pressure versus spinal cord perfusion pressure had an inverted U-shaped relation (Ȓ2 = 0.82), with the highest resting anal pressures being at a spinal cord perfusion pressure of approximately 100 mmHg. The recto-anal inhibitory reflex (transient relaxation of the internal anal sphincter during rectal distension), which is important for maintaining fecal continence, was present in 90% of attempts at high (90 mmHg) spinal cord perfusion pressure versus 70% of attempts at low (60 mmHg) spinal cord perfusion pressure (P < 0.05). During cough, the rise in anal pressure from baseline was 51 cmH2O at high (86 mmHg) spinal cord perfusion pressure versus 37 cmH2O at low (62 mmHg) spinal cord perfusion pressure (P < 0.0001). During anal squeeze, higher spinal cord perfusion pressure was associated with longer endurance time and spinal cord perfusion pressure of 70-90 mmHg was associated with stronger squeeze. There were no complications associated with anorectal manometry.ConclusionsOur data indicate that spinal cord injury causes severe disruption of anal sphincter function. Several key components of anal continence (resting anal pressure, recto-anal inhibitory reflex, and anal pressure during cough and squeeze) markedly improve at higher spinal cord perfusion pressure. Maintaining too high of spinal cord perfusion pressure may worsen anal continence.
| S-EPMC8692299 | biostudies-literature
Project description:BACKGROUND:Pregnant women with congenital or acquired spinal cord injury face challenges due to compromised neurologic function and mobility, factors that may also affect fetal/infant health. Few studies have examined pregnancy course and longer-term outcomes in this population. OBJECTIVE:To assess pregnancy outcomes among women with spinal cord injury, paralysis, or spina bifida using population-based data. DESIGN:Retrospective cohort study. SETTING:Washington state linked birth-hospital discharge records. PARTICIPANTS:All women (N = 529) with spinal cord injury, paralysis, or spina bifida with singleton live birth deliveries 1987-2012, and a comparison group of women without disabilities (N = 5282). METHODS:Diagnosis codes were screened to identify cases and a 10:1 random sample of comparison women. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated overall and separately for each condition using multivariable regression. Subsequent hospitalizations or death were identified via linkage to hospital discharge/death records for 2 years after delivery. MAIN OUTCOME MEASUREMENTS:Pregnancy course (weight gain, gestational diabetes, preeclampsia, infection, venous thromboembolism), delivery/labor characteristics, infant characteristics (birthweight/size, gestational age), and longer-term outcomes (occurrence/reasons for maternal/infant rehospitalization, mortality). RESULTS:Women with these spinal conditions had increased adjusted risks of prenatal urinary tract infection/pyelonephritis (RR 26.43, 95% CI 13.97-49.99), venous thromboembolism (RR 9.16, 95% CI 2.17-38.60), preterm rupture of membranes (RR 2.15, 95% CI 1.18-3.90), and cesarean delivery (RR 1.88, 95% CI 1.70-2.09). They had longer hospitalizations and increased rehospitalization (RR 1.54, 95% CI 1.28-1.87), including for postpartum depression (RR 8.15, 4.29-15.48) or injury (RR 13.05, 95% CI 6.60-25.81). Their infants were more often small for gestational age (RR 1.65, 95% CI 1.33-2.06), but had no increased risk of rehospitalization or death. CONCLUSIONS:We observed no increased long-term morbidity among infants of women with these conditions. Possible increased maternal morbidities during the first postpartum years indicate areas for intervention. LEVEL OF EVIDENCE:III.
| S-EPMC6675642 | biostudies-literature