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1.
Sci Adv ; 10(19): eadl1230, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38718109

ABSTRACT

The spinal cord is crucial for transmitting motor and sensory information between the brain and peripheral systems. Spinal cord injuries can lead to severe consequences, including paralysis and autonomic dysfunction. We introduce thin-film, flexible electronics for circumferential interfacing with the spinal cord. This method enables simultaneous recording and stimulation of dorsal, lateral, and ventral tracts with a single device. Our findings include successful motor and sensory signal capture and elicitation in anesthetized rats, a proof-of-concept closed-loop system for bridging complete spinal cord injuries, and device safety verification in freely moving rodents. Moreover, we demonstrate potential for human application through a cadaver model. This method sees a clear route to the clinic by using materials and surgical practices that mitigate risk during implantation and preserve cord integrity.


Subject(s)
Spinal Cord Injuries , Spinal Cord , Animals , Spinal Cord/physiology , Rats , Spinal Cord Injuries/therapy , Spinal Cord Injuries/physiopathology , Humans , Electric Stimulation/methods , Electrodes, Implanted
2.
Int J Nanomedicine ; 19: 4081-4101, 2024.
Article in English | MEDLINE | ID: mdl-38736654

ABSTRACT

Purpose: Spinal cord injury (SCI) is an incurable and disabling event that is accompanied by complex inflammation-related pathological processes, such as the production of excessive reactive oxygen species (ROS) by infiltrating inflammatory immune cells and their release into the extracellular microenvironment, resulting in extensive apoptosis of endogenous neural stem cells. In this study, we noticed the neuroregeneration-promoting effect as well as the ability of the innovative treatment method of FTY720-CDs@GelMA paired with NSCs to increase motor function recovery in a rat spinal cord injury model. Methods: Carbon dots (CDs) and fingolimod (FTY720) were added to a hydrogel created by chemical cross-linking GelMA (FTY720-CDs@GelMA). The basic properties of FTY720-CDs@GelMA hydrogels were investigated using TEM, SEM, XPS, and FTIR. The swelling and degradation rates of FTY720-CDs@GelMA hydrogels were measured, and each group's ability to scavenge reactive oxygen species was investigated. The in vitro biocompatibility of FTY720-CDs@GelMA hydrogels was assessed using neural stem cells. The regeneration of the spinal cord and recovery of motor function in rats were studied following co-treatment of spinal cord injury using FTY720-CDs@GelMA hydrogel in combination with NSCs, utilising rats with spinal cord injuries as a model. Histological and immunofluorescence labelling were used to determine the regeneration of axons and neurons. The recovery of motor function in rats was assessed using the BBB score. Results: The hydrogel boosted neurogenesis and axonal regeneration by eliminating excess ROS and restoring the regenerative environment. The hydrogel efficiently contained brain stem cells and demonstrated strong neuroprotective effects in vivo by lowering endogenous ROS generation and mitigating ROS-mediated oxidative stress. In a follow-up investigation, we discovered that FTY720-CDs@GelMA hydrogel could dramatically boost NSC proliferation while also promoting neuronal regeneration and synaptic formation, hence lowering cavity area. Conclusion: Our findings suggest that the innovative treatment of FTY720-CDs@GelMA paired with NSCs can effectively improve functional recovery in SCI patients, making it a promising therapeutic alternative for SCI.


Subject(s)
Fingolimod Hydrochloride , Hydrogels , Neural Stem Cells , Rats, Sprague-Dawley , Spinal Cord Injuries , Animals , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/therapy , Fingolimod Hydrochloride/pharmacology , Fingolimod Hydrochloride/chemistry , Fingolimod Hydrochloride/administration & dosage , Neural Stem Cells/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/administration & dosage , Rats , Recovery of Function/drug effects , Reactive Oxygen Species/metabolism , Quantum Dots/chemistry , Disease Models, Animal , Female , Spinal Cord/drug effects
3.
Drug Des Devel Ther ; 18: 1399-1414, 2024.
Article in English | MEDLINE | ID: mdl-38707612

ABSTRACT

Hydrogen, which is a novel biomedical molecule, is currently the subject of extensive research involving animal experiments and in vitro cell experiments, and it is gradually being applied in clinical settings. Hydrogen has been proven to possess anti-inflammatory, selective antioxidant, and antiapoptotic effects, thus exhibiting considerable protective effects in various diseases. In recent years, several studies have provided preliminary evidence for the protective effects of hydrogen on spinal cord injury (SCI). This paper provides a comprehensive review of the potential molecular biology mechanisms of hydrogen therapy and its application in treating SCI, with an aim to better explore the medical value of hydrogen and provide new avenues for the adjuvant treatment of SCI.


Subject(s)
Hydrogen , Spinal Cord Injuries , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/metabolism , Hydrogen/pharmacology , Hydrogen/chemistry , Humans , Animals , Antioxidants/pharmacology , Antioxidants/chemistry , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Apoptosis/drug effects , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry
4.
Pain ; 165(6): 1336-1347, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38739766

ABSTRACT

ABSTRACT: Evidence from previous studies supports the concept that spinal cord injury (SCI)-induced neuropathic pain (NP) has its neural roots in the peripheral nervous system. There is uncertainty about how and to which degree mechanoreceptors contribute. Sensorimotor activation-based interventions (eg, treadmill training) have been shown to reduce NP after experimental SCI, suggesting transmission of pain-alleviating signals through mechanoreceptors. The aim of the present study was to understand the contribution of mechanoreceptors with respect to mechanical allodynia in a moderate mouse contusion SCI model. After genetic ablation of tropomyosin receptor kinase B expressing mechanoreceptors before SCI, mechanical allodynia was reduced. The identical genetic ablation after SCI did not yield any change in pain behavior. Peptidergic nociceptor sprouting into lamina III/IV below injury level as a consequence of SCI was not altered by either mechanoreceptor ablation. However, skin-nerve preparations of contusion SCI mice 7 days after injury yielded hyperexcitability in nociceptors, not in mechanoreceptors, which makes a substantial direct contribution of mechanoreceptors to NP maintenance unlikely. Complementing animal data, quantitative sensory testing in human SCI subjects indicated reduced mechanical pain thresholds, whereas the mechanical detection threshold was not altered. Taken together, early mechanoreceptor ablation modulates pain behavior, most likely through indirect mechanisms. Hyperexcitable nociceptors seem to be the main drivers of SCI-induced NP. Future studies need to focus on injury-derived factors triggering early-onset nociceptor hyperexcitability, which could serve as targets for more effective therapeutic interventions.


Subject(s)
Disease Models, Animal , Hyperalgesia , Mechanoreceptors , Mice, Inbred C57BL , Spinal Cord Injuries , Animals , Spinal Cord Injuries/complications , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/physiopathology , Mice , Hyperalgesia/physiopathology , Hyperalgesia/etiology , Hyperalgesia/metabolism , Mechanoreceptors/metabolism , Mechanoreceptors/physiology , Male , Humans , Pain Threshold/physiology , Female , Pain Measurement , Mice, Transgenic , Neuralgia/etiology , Neuralgia/metabolism , Neuralgia/physiopathology
5.
J Rehabil Med ; 56: jrm34732, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698655

ABSTRACT

OBJECTIVE: To investigate (i) psychometric properties of the Danish version of the Caregiver Burden Scale, (ii) predictors of burden in caregivers of persons with stroke, spinal cord injury, or traumatic brain injury, and (iii) severity of caregiver burden, and compare level of severity of burden in caregivers of persons with stroke, spinal cord injury, or traumatic brain injury. DESIGN: Cross-sectional study. PARTICIPANTS: Pooled sample of 122 caregivers. METHODS: Psychometric properties including internal consistency, floor and ceiling effects, inter-item and item-total correlation were investigated using the Caregiver Burden Scale. Severity of burden was compared using Fisher's exact test and ANOVA, and predictors of burden were investigated using multiple linear regression models. RESULTS: The total burden score exhibited good internal consistency (α = 0.93), with no floor or ceiling effects. Longer time as a caregiver was a significant predictor of higher total score. The majority (52.2%) reported a low level of caregiver burden (below cut-off of 2.00). Mean scores on the Caregiver Burden Scale were not significantly different among caregivers across diagnostic groups. Differences were found when comparing spinal cord injury caregivers with brain injury caregivers (traumatic brain injury and stroke, collectively), χ2(2) = 6.38, p = 0.04, as spinal cord injury caregivers were more likely to report low levels of burden. CONCLUSION: Good psychometric properties were reported, and most caregivers reported a low level of burden, and longer time as a caregiver was associated with higher burden. Consequently, the Caregiver Burden Scale is a valid measure to use when measuring burden in caregivers of stroke, spinal cord injury, and traumatic brain injury patients.


Subject(s)
Brain Injuries, Traumatic , Caregiver Burden , Caregivers , Psychometrics , Spinal Cord Injuries , Stroke , Humans , Spinal Cord Injuries/psychology , Spinal Cord Injuries/rehabilitation , Female , Male , Cross-Sectional Studies , Middle Aged , Brain Injuries, Traumatic/psychology , Stroke/psychology , Adult , Caregivers/psychology , Caregiver Burden/psychology , Denmark , Surveys and Questionnaires , Aged , Cost of Illness , Reproducibility of Results
6.
Cells ; 13(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38727295

ABSTRACT

Strain differences have been reported for motor behaviors, and only a subset of spinal cord injury (SCI) patients develop neuropathic pain, implicating genetic or genomic contribution to this condition. Here, we evaluated neuropsychiatric behaviors in A/J, BALB/c, and C57BL/6 male mice and tested genetic or genomic alterations following SCI. A/J and BALB/c naive mice showed significantly less locomotor activity and greater anxiety-like behavior than C57BL/6 mice. Although SCI elicited locomotor dysfunction, C57BL/6 and A/J mice showed the best and the worst post-traumatic recovery, respectively. Mild (m)-SCI mice showed deficits in gait dynamics. All moderate/severe SCI mice exhibited similar degrees of anxiety/depression. mSCI in BALB/c and A/J mice resulted in depression, whereas C57BL/6 mice did not exhibit depression. mSCI mice had significantly lower mechanical thresholds than their controls, indicating high cutaneous hypersensitivity. C57BL/6, but not A/J and BLAB/c mice, showed significantly lower heat thresholds than their controls. C57BL/6 mice exhibited spontaneous pain. RNAseq showed that genes in immune responses and wound healing were upregulated, although A/J mice showed the largest increase. The cell cycle and the truncated isoform of trkB genes were robustly elevated in SCI mice. Thus, different genomics are associated with post-traumatic recovery, underscoring the likely importance of genetic factors in SCI.


Subject(s)
Depression , Hyperalgesia , Locomotion , Spinal Cord Injuries , Animals , Spinal Cord Injuries/genetics , Spinal Cord Injuries/physiopathology , Hyperalgesia/genetics , Locomotion/genetics , Mice , Depression/genetics , Depression/physiopathology , Male , Mice, Inbred C57BL , Disease Models, Animal , Species Specificity
7.
Article in English | MEDLINE | ID: mdl-38739520

ABSTRACT

Robotic systems, such as Lokomat® have shown promising results in people with severe motor impairments, who suffered a stroke or other neurological damage. Robotic devices have also been used by people with more challenging damages, such as Spinal Cord Injury (SCI), using feedback strategies that provide information about the brain activity in real-time. This study proposes a novel Motor Imagery (MI)-based Electroencephalogram (EEG) Visual Neurofeedback (VNFB) system for Lokomat® to teach individuals how to modulate their own µ (8-12 Hz) and ß (15-20 Hz) rhythms during passive walking. Two individuals with complete SCI tested our VNFB system completing a total of 12 sessions, each on different days. For evaluation, clinical outcomes before and after the intervention and brain connectivity were analyzed. As findings, the sensitivity related to light touch and painful discrimination increased for both individuals. Furthermore, an improvement in neurogenic bladder and bowel functions was observed according to the American Spinal Injury Association Impairment Scale, Neurogenic Bladder Symptom Score, and Gastrointestinal Symptom Rating Scale. Moreover, brain connectivity between different EEG locations significantly ( [Formula: see text]) increased, mainly in the motor cortex. As other highlight, both SCI individuals enhanced their µ rhythm, suggesting motor learning. These results indicate that our gait training approach may have substantial clinical benefits in complete SCI individuals.


Subject(s)
Electroencephalography , Gait , Neurofeedback , Spinal Cord Injuries , Humans , Spinal Cord Injuries/rehabilitation , Spinal Cord Injuries/physiopathology , Neurofeedback/methods , Electroencephalography/methods , Male , Adult , Gait/physiology , Robotics , Imagination/physiology , Female , Gait Disorders, Neurologic/rehabilitation , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Treatment Outcome , Middle Aged , Exoskeleton Device , Walking/physiology , Beta Rhythm , Imagery, Psychotherapy/methods
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(4): 636-643, 2024 Apr 20.
Article in Chinese | MEDLINE | ID: mdl-38708495

ABSTRACT

OBJECTIVE: To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. METHODS: Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. RESULTS: The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. CONCLUSION: Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.


Subject(s)
Astrocytes , Pyruvate Kinase , Rats, Sprague-Dawley , Signal Transduction , Spinal Cord Injuries , YAP-Signaling Proteins , Animals , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/drug therapy , Rats , Astrocytes/metabolism , Astrocytes/drug effects , Signal Transduction/drug effects , Thyroid Hormone-Binding Proteins , Thyroid Hormones/metabolism , Carrier Proteins/metabolism , Drugs, Chinese Herbal/pharmacology , Disease Models, Animal , Membrane Proteins/metabolism
9.
WMJ ; 123(2): 88-94, 2024 May.
Article in English | MEDLINE | ID: mdl-38718235

ABSTRACT

INTRODUCTION: Traumatic spinal cord injury (tSCI) is a devastating event that can cause permanent loss of function or disability. Time to surgical decompression of the spinal cord affects outcomes and is a critical principle in management of tSCI. One of the major determinants of time to decompression is transport time. To date, no study has compared the neurological outcomes of tSCI patients transported via ground/ambulance versus air/helicopter. OBJECTIVE: This retrospective cohort study sought to assess the association of the mode of transport on the neurological outcomes of tSCI patients. METHODS: Data from 46 ground transport and 29 air transport patients with tSCI requiring surgical decompression were collected. Outcomes were assessed by the change in American Spinal Injury Association Impairment Scale (AIS) grade from admission to discharge. Additionally, the utilization of air versus ground transport was assessed based on the distance from the admitting institution. RESULTS: Among the transport groups, there were no significant differences (PP < 0.05) in patient demographics. Helicopter transport patients demonstrated higher rates of AIS grade improvement (P = 0.004), especially among AIS grade A/grade B patients (P = 0.02; P = 0.02, respectively), compared to the ambulance transport group. Additionally, within the cohort of patients undergoing decompression within 0 to 12 hours, helicopter transport was associated with higher AIS grade improvement (P = 0.04) versus the ambulance transport group. Helicopter transport was used more frequently at distances greater than 80 miles from the admitting institution (P = 0.01). CONCLUSIONS: This study suggests that helicopter transport of tSCI patients requiring surgical decompression was associated with improved neurological outcomes compared to patients transported via ambulance.


Subject(s)
Air Ambulances , Ambulances , Decompression, Surgical , Spinal Cord Injuries , Humans , Spinal Cord Injuries/therapy , Female , Male , Retrospective Studies , Middle Aged , Adult , Treatment Outcome , Wisconsin/epidemiology
10.
J Neuroeng Rehabil ; 21(1): 73, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38705999

ABSTRACT

BACKGROUND: Exoskeletons are increasingly applied during overground gait and balance rehabilitation following neurological impairment, although optimal parameters for specific indications are yet to be established. OBJECTIVE: This systematic review aimed to identify dose and dosage of exoskeleton-based therapy protocols for overground locomotor training in spinal cord injury/disease. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items Systematic Reviews and Meta-Analyses guidelines. A literature search was performed using the CINAHL Complete, Embase, Emcare Nursing, Medline ALL, and Web of Science databases. Studies in adults with subacute and/or chronic spinal cord injury/disease were included if they reported (1) dose (e.g., single session duration and total number of sessions) and dosage (e.g., frequency of sessions/week and total duration of intervention) parameters, and (2) at least one gait and/or balance outcome measure. RESULTS: Of 2,108 studies identified, after removing duplicates and filtering for inclusion, 19 were selected and dose, dosage and efficacy were abstracted. Data revealed a great heterogeneity in dose, dosage, and indications, with overall recommendation of 60-min sessions delivered 3 times a week, for 9 weeks in 27 sessions. Specific protocols were also identified for functional restoration (60-min, 3 times a week, for 8 weeks/24 sessions) and cardiorespiratory rehabilitation (60-min, 3 times a week, for 12 weeks/36 sessions). CONCLUSION: This review provides evidence-based best practice recommendations for overground exoskeleton training among individuals with spinal cord injury/disease based on individual therapeutic goals - functional restoration or cardiorespiratory rehabilitation. There is a need for structured exoskeleton clinical translation studies based on standardized methods and common therapeutic outcomes.


Subject(s)
Exercise Therapy , Exoskeleton Device , Postural Balance , Spinal Cord Injuries , Spinal Cord Injuries/rehabilitation , Humans , Postural Balance/physiology , Exercise Therapy/methods , Exercise Therapy/instrumentation , Gait/physiology , Gait Disorders, Neurologic/rehabilitation , Gait Disorders, Neurologic/etiology
11.
PLoS One ; 19(5): e0303235, 2024.
Article in English | MEDLINE | ID: mdl-38728287

ABSTRACT

Excitotoxicity represents the primary cause of neuronal death following spinal cord injury (SCI). While autophagy plays a critical and intricate role in SCI, the specific mechanism underlying the relationship between excitotoxicity and autophagy in SCI has been largely overlooked. In this study, we isolated primary spinal cord neurons from neonatal rats and induced excitotoxic neuronal injury by high concentrations of glutamic acid, mimicking an excitotoxic injury model. Subsequently, we performed transcriptome sequencing. Leveraging machine learning algorithms, including weighted correlation network analysis (WGCNA), random forest analysis (RF), and least absolute shrinkage and selection operator analysis (LASSO), we conducted a comprehensive investigation into key genes associated with spinal cord neuron injury. We also utilized protein-protein interaction network (PPI) analysis to identify pivotal proteins regulating key gene expression and analyzed key genes from public datasets (GSE2599, GSE20907, GSE45006, and GSE174549). Our findings revealed that six genes-Anxa2, S100a10, Ccng1, Timp1, Hspb1, and Lgals3-were significantly upregulated not only in vitro in neurons subjected to excitotoxic injury but also in rats with subacute SCI. Furthermore, Hspb1 and Lgals3 were closely linked to neuronal autophagy induced by excitotoxicity. Our findings contribute to a better understanding of excitotoxicity and autophagy, offering potential targets and a theoretical foundation for SCI diagnosis and treatment.


Subject(s)
Autophagy , Galectin 3 , Machine Learning , Neurons , Animals , Neurons/metabolism , Rats , Galectin 3/metabolism , Galectin 3/genetics , Rats, Sprague-Dawley , Molecular Chaperones/genetics , Molecular Chaperones/metabolism , Spinal Cord/metabolism , Spinal Cord/pathology , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/pathology , Spinal Cord Injuries/genetics , Protein Interaction Maps , Glutamic Acid/metabolism , Heat-Shock Proteins/metabolism , Heat-Shock Proteins/genetics
12.
PLoS One ; 19(5): e0303342, 2024.
Article in English | MEDLINE | ID: mdl-38728306

ABSTRACT

This study protocol aims to investigate how localised cooling influences the skin's microvascular, inflammatory, structural, and perceptual tolerance to sustained mechanical loading at the sacrum, evaluating factors such as morphology, physiology, and perceptual responses. The protocol will be tested on individuals of different age, sex, skin tone and clinical status, using a repeated-measure design with three participants cohorts: i) young healthy (n = 35); ii) older healthy (n = 35); iii) spinal cord injured (SCI, n = 35). Participants will complete three testing sessions during which their sacrum will be mechanically loaded (60 mmHg; 45 min) and unloaded (20 min) with a custom-built thermal probe, causing pressure-induced ischemia and post-occlusive reactive hyperaemia. Testing sessions will differ by the probe's temperature, which will be set to either 38°C (no cooling), 24°C (mild cooling), or 16°C (strong cooling). We will measure skin blood flow (via Laser Doppler Flowmetry; 40 Hz); pro- and anti-inflammatory biomarkers in skin sebum (Sebutape); structural skin properties (Optical Coherence Tomography); and ratings of thermal sensation, comfort, and acceptance (Likert Scales); throughout the loading and unloading phases. Changes in post-occlusive reactive hyperaemia will be considered as the primary outcome and data will be analysed for the independent and interactive effects of stimuli's temperature and of participant group on within- and between-subject mean differences (and 95% Confidence Intervals) in peak hyperaemia, by means of a 2-way mixed model ANOVA (or Friedman). Regression models will also be developed to assess the relationship between absolute cooling temperatures and peak hyperaemia. Secondary outcomes will be within- and between-subject mean changes in biomarkers' expression, skin structural and perceptual responses. This analysis will help identifying physiological and perceptual thresholds for the protective effects of cooling from mechanically induced damage underlying the development of pressure ulcers in individuals varying in age and clinical status.


Subject(s)
Sacrum , Skin , Humans , Skin/blood supply , Adult , Male , Female , Middle Aged , Young Adult , Inflammation , Spinal Cord Injuries/physiopathology , Cold Temperature , Aged , Microvessels/physiopathology , Weight-Bearing , Skin Temperature
13.
Spinal Cord Ser Cases ; 10(1): 34, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714676

ABSTRACT

Professor Robert Lipschitz, MB, ChB, PhD(Med), FRCS(Edin) was a pioneer who established the Spinal Cord Injury Unit, at Chris Hani Baragwanath Hospital, Soweto, Johannesburg, South Africa. A brief description of his academic and clinical accomplishments is given.


Subject(s)
Spinal Cord Injuries , South Africa , Spinal Cord Injuries/history , Spinal Cord Injuries/therapy , Humans , History, 20th Century , History, 21st Century
14.
Cells ; 13(10)2024 May 10.
Article in English | MEDLINE | ID: mdl-38786039

ABSTRACT

Spinal cord injury (SCI) can result in the permanent loss of mobility, sensation, and autonomic function. Secondary degeneration after SCI both initiates and propagates a hostile microenvironment that is resistant to natural repair mechanisms. Consequently, exogenous stem cells have been investigated as a potential therapy for repairing and recovering damaged cells after SCI and other CNS disorders. This focused review highlights the contributions of mesenchymal (MSCs) and dental stem cells (DSCs) in attenuating various secondary injury sequelae through paracrine and cell-to-cell communication mechanisms following SCI and other types of neurotrauma. These mechanistic events include vascular dysfunction, oxidative stress, excitotoxicity, apoptosis and cell loss, neuroinflammation, and structural deficits. The review of studies that directly compare MSC and DSC capabilities also reveals the superior capabilities of DSC in reducing the effects of secondary injury and promoting a favorable microenvironment conducive to repair and regeneration. This review concludes with a discussion of the current limitations and proposes improvements in the future assessment of stem cell therapy through the reporting of the effects of DSC viability and DSC efficacy in attenuating secondary damage after SCI.


Subject(s)
Spinal Cord Injuries , Spinal Cord Injuries/therapy , Spinal Cord Injuries/pathology , Spinal Cord Injuries/complications , Humans , Animals , Stem Cells , Stem Cell Transplantation , Mesenchymal Stem Cells
15.
Nat Med ; 30(5): 1276-1283, 2024 May.
Article in English | MEDLINE | ID: mdl-38769431

ABSTRACT

Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARCEX Therapy to improve arm and hand functions in people with chronic SCI. ARCEX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARCEX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARCEX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARCEX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472 .


Subject(s)
Arm , Hand , Quadriplegia , Spinal Cord Injuries , Humans , Quadriplegia/therapy , Quadriplegia/physiopathology , Male , Hand/physiopathology , Female , Middle Aged , Adult , Arm/physiopathology , Spinal Cord Injuries/therapy , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/rehabilitation , Spinal Cord Stimulation/methods , Treatment Outcome , Quality of Life , Prospective Studies , Chronic Disease , Aged , Electric Stimulation Therapy/methods , Electric Stimulation Therapy/adverse effects
16.
Nat Commun ; 15(1): 4331, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773121

ABSTRACT

The adult zebrafish spinal cord displays an impressive innate ability to regenerate after traumatic insults, yet the underlying adaptive cellular mechanisms remain elusive. Here, we show that while the cellular and tissue responses after injury are largely conserved among vertebrates, the large-size fast spinal zebrafish motoneurons are remarkably resilient by remaining viable and functional. We also reveal the dynamic changes in motoneuron glutamatergic input, excitability, and calcium signaling, and we underscore the critical role of calretinin (CR) in binding and buffering the intracellular calcium after injury. Importantly, we demonstrate the presence and the dynamics of a neuron-to-neuron bystander neuroprotective biochemical cooperation mediated through gap junction channels. Our findings support a model in which the intimate and dynamic interplay between glutamate signaling, calcium buffering, gap junction channels, and intercellular cooperation upholds cell survival and promotes the initiation of regeneration.


Subject(s)
Gap Junctions , Motor Neurons , Spinal Cord Injuries , Spinal Cord , Zebrafish , Animals , Spinal Cord Injuries/metabolism , Spinal Cord/metabolism , Gap Junctions/metabolism , Motor Neurons/metabolism , Calcium/metabolism , Calcium Signaling , Calbindin 2/metabolism , Zebrafish Proteins/metabolism , Zebrafish Proteins/genetics , Glutamic Acid/metabolism , Cell Survival
17.
J Colloid Interface Sci ; 668: 646-657, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38696992

ABSTRACT

Severe spinal cord injury (SCI) leads to dysregulated neuroinflammation and cell apoptosis, resulting in axonal die-back and the loss of neuroelectric signal transmission. While biocompatible hydrogels are commonly used in SCI repair, they lack the capacity to support neuroelectric transmission. To overcome this limitation, we developed an injectable silk fibroin/ionic liquid (SFMA@IL) conductive hydrogel to assist neuroelectric signal transmission after SCI in this study. The hydrogel can form rapidly in situ under ultraviolet (UV) light. The mechanical supporting and neuro-regenerating properties are provided by silk fibroin (SF), while the conductive capability is provided by the designed ionic liquid (IL). SFMA@IL showed attractive features for SCI repair, such as anti-swelling, conductivity, and injectability. In vivo, SFMA@IL hydrogel used in rats with complete transection injuries was found to remodel the microenvironment, reduce inflammation, and facilitate neuro-fiber outgrowth. The hydrogel also led to a notable decrease in cell apoptosis and the achievement of scar-free wound healing, which saved 45.6 ± 10.8 % of spinal cord tissue in SFMA@IL grafting. Electrophysiological studies in rats with complete transection SCI confirmed SFMA@IL's ability to support sensory neuroelectric transmission, providing strong evidence for its signal transmission function. These findings provide new insights for the development of effective SCI treatments.


Subject(s)
Electric Conductivity , Fibroins , Hydrogels , Rats, Sprague-Dawley , Spinal Cord Injuries , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/pathology , Animals , Rats , Hydrogels/chemistry , Hydrogels/pharmacology , Fibroins/chemistry , Fibroins/pharmacology , Injections , Apoptosis/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Particle Size
18.
World Neurosurg ; 185: e99-e142, 2024 May.
Article in English | MEDLINE | ID: mdl-38741332

ABSTRACT

OBJECTIVE: Neurotrauma is a significant cause of morbidity and mortality in Nigeria. We conducted this systematic review to generate nationally generalizable reference data for the country. METHODS: Four research databases and gray literature sources were electronically searched. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies of Interventions and Cochrane's risk of bias tools. Descriptive analysis, narrative synthesis, and statistical analysis (via paired t-tests and χ2 independence tests) were performed on relevant article metrics (α = 0.05). RESULTS: We identified a cohort of 45,763 patients from 254 articles. The overall risk of bias was moderate to high. Most articles employed retrospective cohort study designs (37.4%) and were published during the last 2 decades (81.89%). The cohort's average age was 32.5 years (standard deviation, 20.2) with a gender split of ∼3 males per female. Almost 90% of subjects were diagnosed with traumatic brain injury, with road traffic accidents (68.6%) being the greatest cause. Altered consciousness (48.4%) was the most commonly reported clinical feature. Computed tomography (53.5%) was the most commonly used imaging modality, with skull (25.7%) and vertebral fracture (14.1%) being the most common radiological findings for traumatic brain injury and traumatic spinal injury, respectively. Two-thirds of patients were treated nonoperatively. Outcomes were favorable in 63.7% of traumatic brain injury patients, but in only 20.9% of traumatic spinal injury patients. Pressure sores, infection, and motor deficits were the most commonly reported complications in the latter. CONCLUSIONS: This systematic review and pooled analysis demonstrate the significant burden of neurotrauma across Nigeria.


Subject(s)
Brain Injuries, Traumatic , Humans , Nigeria/epidemiology , Brain Injuries, Traumatic/epidemiology , Brain Injuries, Traumatic/therapy , Female , Male , Adult , Accidents, Traffic/statistics & numerical data , Spinal Cord Injuries/epidemiology , Spinal Cord Injuries/therapy
19.
Article in English | MEDLINE | ID: mdl-38780270

ABSTRACT

Spinal cord injury is associated with spinal vascular disruptions that result in spinal ischemia and tissue hypoxia. This study evaluated the therapeutic efficacy of normobaric hyperoxia on spinal cord oxygenation and circulatory function at the acute stage of cervical spinal cord injury. Adult male Sprague Dawley rats underwent dorsal cervical laminectomy or cervical spinal cord contusion. At 1-2 days after spinal surgery, spinal cord oxygenation was monitored in anesthetized and spontaneously breathing rats through optical recording of oxygen sensor foils placed on the cervical spinal cord and pulse oximetry. The arterial blood pressure, heart rate, blood gases, and peripheral oxyhemoglobin saturation were also measured under hyperoxic (50% O2) and normoxic (21% O2) conditions. The results showed that contused animals had significantly lower spinal cord oxygenation levels than uninjured animals during normoxia. Peripheral oxyhemoglobin saturation, arterial oxygen partial pressure, and mean arterial blood pressure are significantly reduced following cervical spinal cord contusion. Notably, spinal oxygenation of contused rats could be improved to a level comparable to uninjured animals under hyperoxia. Furthermore, acute hyperoxia elevated blood pressure, arterial oxygen partial pressure, and peripheral oxyhemoglobin saturation. These results suggest that normobaric hyperoxia can significantly improve spinal cord oxygenation and circulatory function in the acute phase after cervical spinal cord injury. We propose that adjuvant normobaric hyperoxia combined with other hemodynamic optimization strategies may prevent secondary damage after spinal cord injury and improve functional recovery.


Subject(s)
Hyperoxia , Rats, Sprague-Dawley , Spinal Cord Injuries , Animals , Spinal Cord Injuries/therapy , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/metabolism , Male , Hyperoxia/physiopathology , Hyperoxia/blood , Rats , Oxygen/blood , Oxygen/metabolism , Spinal Cord/metabolism , Spinal Cord/blood supply , Spinal Cord/physiopathology , Cervical Cord/injuries , Cervical Cord/metabolism , Blood Pressure/physiology , Oxyhemoglobins/metabolism , Heart Rate/physiology
20.
J Electromyogr Kinesiol ; 76: 102885, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723398

ABSTRACT

Spinal cord injury (SCI) resulting in complex neuromuscular pathology is not sufficiently well understood. To better quantify neuromuscular changes after SCI, this study uses a clustering index (CI) method for surface electromyography (sEMG) clustering representation to investigate the relation between sEMG and torque in SCI survivors. The sEMG signals were recorded from 13 subjects with SCI and 13 gender-age matched able-bodied subjects during isometric contraction of the biceps brachii muscle at different torque levels using a linear electrode array. Two torque representations, maximum voluntary contraction (MVC%) and absolute torque, were used. CI values were calculated for sEMG. Regression analyses were performed on CI values and torque levels of elbow flexion, revealing a strong linear relationship. The slopes of regressions between SCI survivors and control subjects were compared. The findings indicated that the range of distribution of CI values and slopes was greater in subjects with SCI than in control subjects (p < 0.05). The increase or decrease in slope was also observed at the individual level. This suggests that the CI and its sEMG clustering-torque relation may serve as valuable quantitative indicators for determining neuromuscular lesions after SCI, contributing to the development of effective rehabilitation strategies for improving motor performance.


Subject(s)
Electromyography , Muscle, Skeletal , Spinal Cord Injuries , Humans , Spinal Cord Injuries/physiopathology , Electromyography/methods , Male , Female , Adult , Muscle, Skeletal/physiopathology , Cluster Analysis , Torque , Isometric Contraction/physiology , Middle Aged
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