Effectiveness of respiratory proprioceptive neuromuscular facilitation technique on pulmonary function in spinal cord injury patients: a randomized controlled trial

Background: Spinal cord injury (SCI) often leads to respiratory complications due to impaired neuromuscular control. Proprioceptive neuromuscular facilitation (PNF) techniques have shown promise in improving respiratory function in various populations, but their effectiveness in SCI patients remains underexplored. This study aimed to investigate the effectiveness of respiratory PNF techniques on pulmonary function in individuals with SCI. Methods: A randomized controlled trial was conducted involving SCI patients with respiratory impairment. A total of 43 participants were included in this study. The study duration was 4 years with an intervention period of 4 weeks and the outcome measures were pulmonary functions and chest expansion using inch tape. Results: There was a significant improvement in pulmonary functions in the control group and a highly significant improvement in pulmonary functions in the experimental group after 4 weeks of interventions and chest expansion was significantly improved in the experimental group. Conclusions: The respiratory PNF techniques demonstrated a clinically meaningful enhancement in pulmonary function and chest mobility among SCI patients. Respiratory PNF techniques represent a valuable adjunct therapy for improving pulmonary function and chest mobility in individuals with SCI.

Unexpected clinical and functional recovery in patients with chronic traumatic chronic spinal cord injury: a case series

Motor recovery in traumatic spinal cord injury (tSCI) is reported to reach its plateau by 1 year and maximum recovery period is reported to be 2 years. Acute rehabilitation is very well documented in literature with patients reporting for functional rehabilitation immediately after shock period is over. However, the scenario being a bit different in rural areas with comparatively less awareness about role of physiotherapy, patients with tSCI reports at later stages. Reported here is a series of chronic tSCI cases who showed remarkable clinical and functional recovery in short time. Aim of this study is to report recovery in patients with chronic tSCI and to compare the patient outcomes with expected outcomes. Conventional physiotherapy was given 5 days a week with minimum 45 mins treatment. Baseline assessment at admission and at discharge was recoded. Improvement was recorded with spinal cord independence at different time points. Nine patients below 40 years of age, average duration of injury 6.2 years were treated for average of 8 months. NLI did not change in 3 patients whereas in 6 patients NLI moved 2 segments down. Mean change in SCIM score was 10 between admission and discharge. Functional status was compared with expected parameters and was found to be improved by 70%, suggesting had they come at early stage, expected recovery could have been achieved. Clinical and functional recovery in patients with tSCI may occur even after 2 years post injury.

Influences of Glabridin Treatment on Motor Function Recovery after Spinal Cord Injury / Influencia del Tratamiento con Glabridina en la Recuperación de la Función Motora después de una Lesión de la Médula Espinal

SUMMARY: Spinal cord injury (SCI) usually arises from compression due to traffic accidents and falls, resulting in varying degrees of movement, sensory loss, and possible paralysis. Glabridin (Gla) is a natural compound derived from licorice. It significantly affects drug development and medicine because of its anti-inflammatory, anti-oxidative, anti-tumoral, antibacterial, bone protective, cardiovascular protective, neuroprotective, liver protective, anti-obesity, and anti-diabetic properties. Various methods were employed to administer Gla to SCI mice in order to investigate its impact on the recovery of motor function. The mice were allocated into four cohorts using a randomization procedure. In the sham cohort, solely the lamina of vertebral arch was surgically exposed without causing any harm to the spinal cord tissue. Conversely, the injury cohort was subjected to spinal cord tissue damage and received no treatment thereafter. The mice in the remaining two cohorts received a dosage of 40 mg/kg Gla every two days via either intraperitoneal or intrathecal injection for a duration of 42 d following spinal cord injury. We conducted behavioral tests utilizing the Basso Mouse Scale score and gait analysis techniques. Magnetic resonance imaging and hematoxylin and eosin were employed to evaluate scar tissue formation. Systemic inflammation in mice was evaluated by employing an enzyme-linked immunosorbent assay. Gla promoted motor function recovery in mice following SCI and improved the pathological environment in the damaged area. These alterations were more evident in mice subjected to the intrathecal injection method. Intraperitoneal injections appear to be more beneficial for controlling systemic inflammatory responses. Although more intensive studies are required, Gla exhibits promising clinical potential as a cost-effective dietary phytochemical.

La lesión de la médula espinal (LME) generalmente surge de la compresión producto de caídas y accidentes de tránsito, lo que resulta en alteraciones del movimiento, pérdida sensorial y posible parálisis. La Glabridina (Gla) es un compuesto natural derivado del regaliz, constituyéndose en un aporte significativo para el desarrollo de fármacos y la medicina debido a sus propiedades antiinflamatorias, antioxidantes, antitumorales, antibacterianas, osteoprotectoras, cardioprotectoras, neuroprotectoras, hepatoprotectoras, antidiabéticas y contra la obesidad. En el presente trabajo se emplearon varios métodos para administrar Gla a ratones con lesión medular con el fin de investigar su impacto en la recuperación de la función motora. Los ratones fueron distribuidos en cuatro grupos mediante un procedimiento de aleatorización. En el grupo simulado, únicamente se expuso quirúrgicamente la lámina del arco vertebral sin causar ningún daño al tejido de la médula espinal. Por el contrario, el grupo lesionado fue sometido a daño del tejido de la médula espinal, sin recibir tratamiento posterior. Los ratones de los dos grupos restantes recibieron una dosis de 40 mg/kg de Gla cada dos días mediante inyección intraperitoneal o intratecal durante 42 días después de la lesión de la médula espinal. Fueron realizadas pruebas de comportamiento utilizando la puntuación de la escala Basso Mouse y técnicas de análisis de la marcha. Se emplearon imágenes por resonancia magnética y se aplicaron tinciones histológicas (Hematoxilina & Eosina) en muestras para evaluar la formación de tejido cicatricial. La inflamación sistémica en ratones se evaluó mediante el empleo de un ensayo inmunoabsorbente ligado a enzimas. Gla promovió la recuperación de la función motora en ratones después de una lesión medular y mejoró el entorno patológico en el área dañada. Estas alteraciones fueron más evidentes en ratones sometidos al método de inyección intratecal. Las inyecciones intraperitoneales parecen ser más beneficiosas para controlar las respuestas inflamatorias sistémicas. Aunque se requieren estudios más intensivos, Gla exhibe un potencial clínico prometedor como fitoquímico dietético rentable.

Habilidades nas transferências para desempenho das atividades cotidianas de pessoas com lesão da medula espinal / Skills in transfers to perform the daily activities of people with spinal cord injury / Habilidades en transferencias para realizar las actividades diarias de personas con lesión médula espinal

Objetivo: refletir sobre a importância do trabalho das equipes de reabilitação, orientando e habilitando os cadeirantes para o desempenho seguro das transferências diárias, fundamentais na realização das atividades cotidianas e inclusão social. Métodos: trata-se de estudo teórico-reflexivo fundamentado na teoria do déficit de autocuidado, com a utilização integrada dos diagnósticos de enfermagem, da classificação internacional das práticas de enfermagem e do instrumento de avaliação das transferências, adequados às necessidades de pessoas com lesão medular, atendidas nos ambientes institucionais de cuidados, visando o preparo para o desempenho das atividades cotidianas. Resultados: cabe aos enfermeiros assumir liderança nas equipes de reabilitação física, norteando suas intervenções no treinamento dessas pessoas e seus cuidadores para o desempenho e ajuda segura nas transferências para cuidar de si. Conclusão: considerando a lesão medular entre os maiores problemas da saúde coletiva que afeta a humanidade contemporânea, tanto pelos comprometimentos na qualidade de vida das pessoas, quanto no aumento das despesas hospitalares e reabilitação requeridos, a adoção de estratégias de cuidados preventivos de complicações musculoesqueléticas é sempre bem-vinda. Essas pessoas, quando não orientadas, executam movimentos repetitivos para se deslocar em transferências de uma superfície para outra, correndo elevados riscos de contrair lesões nas articulações, pele e mucosas. (AU)

Objective: to reflect on the importance of the work of rehabilitation teams, guiding and enabling wheelchair users to safely perform daily transfers, essential for carrying out daily activities and social inclusion. Methods: this is a theoretical-reflective study based on the theory of self-care deficit, with the integrated use of nursing diagnoses, the international classification of nursing practices and the transfer assessment instrument, adapted to the needs of people with spinal cord injury, attended in institutional care environments, aiming to prepare for the performance of daily activities. Results: it is up to nurses to assume leadership in physical rehabilitation teams, guiding their interventions in the training of these people and their caregivers for performance and safe help in transfers to take care of themselves. Conclusion: considering spinal cord injury among the biggest collective health problems that affect contemporary humanity, both because of the compromises in people's quality of life, as well as the increase in hospital and rehabilitation expenses required, the adoption of preventive care strategies for musculoskeletal complications is always welcome. These people, when not guided, perform repetitive movements to move in transfers from one surface to another, running high risks of contracting injuries to the joints, skin and mucous membranes. (AU)

Objetivo: reflexionar sobre la importancia del trabajo de los equipos de rehabilitación, orientando y capacitando a los usuarios de silla de ruedas para realizar con seguridad las tranferencias cotidianas, indispensables para el desarrollo de las actividades cotidianas y la inclusión social. Métodos: se trata de un estudio teórico-reflexivo basado en la teoría del déficit de autocuidado, con el uso integrado de los diagnósticos de enfermería, la clasificación internacional de prácticas de enfermería y el instrumento de evaluación de la transferencia, adaptado a las necesidades de las personas con lesión medular. asistidos en ambientes de atención institucional, con el objetivo de preparar para el desempeño de las actividades diárias. Resultados: corresponde a los enfermeros asumir el liderazgo en los equipos de rehabilitación física, orientando sus intervenciones en la formación de esas personas y sus cuidadores para el desempeño y ayuda segura en las transferencias para cuidarse. Conclusion: considerando la lesión medular entre los mayores problemas de salud colectiva que afectan a la humanidad contemporánea, tanto por los compromisos en la calidad de vida de las personas, como por el aumento de los gastos hospitalarios y de rehabilitación requeridos, la adopción de estrategias de atención preventiva de las complicaciones musculoesqueléticas siempre es bienvenido Estas personas, cuando no están guiadas, realizan movimientos repetitivos para moverse en transferencias de una superficie a otra, corriendo un alto riesgo de contraer lesiones en las articulaciones, piel y mucosas. (AU)

Impact of COVID-19 on socio-behavioural, health and oral health-related aspects on spinal cord injury patients: a cross-sectional study

Background: Spinal cord injury (SCI) is a damaging, life-altering injury, which is estimated to have an annual global incidence of 40 to 80 cases per million population and is two to five times more possible to die prematurely. This study aims to evaluate the impact of COVID-19 on socio-behavioural, health, and oral health-related aspects of spinal cord injury patients. Methods: This cross-sectional study was conducted among 50 spinal cord injury patients in the rehabilitation center in Chennai, Tamil Nadu, which was conducted between May and June 2022. Results: The comparison of mean distribution scores based on DMFT showed that complete injury patients had a lower DMFT score of 6.40 when compared to incomplete injury (8.41). The periodontal status assessment revealed that SCI with complete injury had a lower mean number of teeth with gingival bleeding and periodontal pocket (3.81 and 2.31 respectively) when compared to incomplete injury (7.12 and 4.49). Moreover, the impact of COVID-19 on the socio-behavior and health status was found to be higher in complete injury than that in incomplete injury patients. Conclusions: Therefore, this pandemic highlights the need to advocate the development of a nationwide SCI registry or surveillance system is fundamental to an understanding of the epidemiology and, hence, the prevention of this emerging health burden.

Clinical Study of Modified Shenqi Pill （肾气丸） Plus Tongdu Tiaoshen Acupuncture （通督调神针刺） for Neurogenic Bladder After Spinal Cord Injury of Kidney-Yang Deficiency Syndrome / 中医杂志

ObjectiveTo observe the clinical efficacy of modified Shenqi Pill （肾气丸） plus Tongdu Tiaoshen Acupuncture （通督调神针刺） in the treatment of neurogenic bladder after spinal cord injury of kidney-yang deficiency syndrome. MethodsForty-six patients were randomly divided into 23 cases each in the control group and the treatment group. Both groups were given conventional treatment， i.e. oral methylcobalamin tablets （0.5 mg each time， 3 times a day） and paraplegic conventional acupuncture （once a day， 6 consecutive days a week）. The control group was given simple bladder function rehabilitation training on the basis of the conventional treatment； and the treatment group was given modified Shenqi Pill orally （1 dose a day， 150 ml each time， taken warmly in morning and evening） and Tongdu Tiaoshen Acupuncture （once a day， 6 consecutive days per week） in addition to what were given to the control group. The treatment course lasted for 4 weeks. The 24 h urination frequency， 24 h urine leakage frequency， 24 h single urine volume， bladder residual urine volume， international lower urinary tract symptom （LUTS） score， traditional Chinese medicine （TCM） syndrome score were compared between the two groups， and clinical effectiveness and TCM syndrome effectiveness were compared between the two groups after treatment. ResultsTwenty patients in each group were finally analyzed in this study. The number of 24 h urination， the number of 24 h urine leakage， bladder residual urine volume， LUTS score， and the TCM syndrome scores decreased after treatment in both groups， and the 24 h single urine volume increased （P＜0.01）； and much more improvement was found of each index in the treatment group than in the control group （P＜0.05 or P＜0.01）. The total clinical effectiveness and TCM syndrome effectiveness in the treatment group was 85.00% （17/20） respectively， which were statistically significantly higher than 45.00% （the total clinical effectiveness， 9/20） and 60.00% （TCM syndrome effectiveness， 12/20） in the control group （P＜0.01）. ConclusionModified Shenqi Pill plus Tongdu Tiaoshen Acupuncture can signi-ficantly improve the clinical symptoms of neurogenic bladder patients after spinal cord injury of kidney-yang deficiency syndrome， having better effectiveness than simple bladder function rehabilitation training， and its mechanism may be related to the improvement of the injured nerve function innervating the bladder.

Long-term efficacy and complications of implantable diaphragm pacer in children with high cervical spinal cord injury: case report and literature review / 中华实用儿科临床杂志

The long-term efficacy and complications of implantable diaphragm pacer (IDP) in a child with cervical spinal cord injury (CSCI) in the Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center in September 2022 were retrospective analyzed.A male child had quadriplegia without an obvious cause at the age of 12 years, and he was then lived completely with the assistance of mechanical ventilation.At the age of 14 years, he could wean off the ventilator in unilateral diaphragmatic pacing mode.However, mechanical ventilation was re-given for months after 5 years due to pneumonia, and then the IDP was re-given with the self-felt decreased pacing effect.After hospitalization, the patient was examined with mild diaphragmatic atrophy, secondary flat chest, and mild scoliosis.After optimization of the transdiaphragmatic pacing threshold and rehabilitation, his respiratory function improved.IDP can be used in CSCI for long time, while flat chest and scoliosis that limited the expansion of the lungs should be considered.At the meantime, the increased abdominal spasm affected the abdominal compliance, leading to the decrease in the efficiency of the diaphragm.

Human umbilical cord mesenchymal stem cell-derived exosomes reduce the permeability of blood-spinal cord barrier after spinal cord injury / 中国组织工程研究

BACKGROUND:Endothelin has been found to be involved in the breakdown of the blood-spinal cord barrier after spinal cord injury,and stem cell-derived exosomes can reduce the permeability of the blood-spinal cord barrier and repair spinal cord injury. OBJECTIVE:To investigate whether exosomes produced by human umbilical cord mesenchymal stem cells can reduce the permeability of the blood-spinal cord barrier by inhibiting endothelin-1 expression,thus repairing spinal cord injury. METHODS:Exosomes were extracted from the cultured supernatant by the hyperspeed centrifugation method.The morphology of exosomes was observed by transmission electron microscope.The expression levels of tsg101 and CD63 were detected by western blot assay.Eighty SD rats were randomly divided into sham operation group,model group,exosome group,and endothelin-1 group(n=20).The modified Allen's method was used to create the rat model of spinal cord injury.In the endothelin-1 group,10 μL(1 μg/mL)endothelin-1 was injected directly into the injured area with a microsyringe.Immediately,1 day,2 days after operation,sham operation group and model group were injected with 200 μL PBS solution through the tail vein;the exosome group and endothelin-1 group were injected with 200 μL exosome(200 μg/mL)solution through the tail vein,respectively.Hind limb motor function scores were performed on days 1,3,7,14 and 21 after spinal cord injury.The blood-spinal cord barrier permeability was observed by Evans blue staining on day 7 after injury.The expression levels of tight junction proteins β-Catenin,ZO-1,Occludin and endothelin-1 in the spinal cord were detected by western blot assay. RESULTS AND CONCLUSION:(1)Basso-Beattie-Bresnahan score in the exosome group was significantly higher than that in the model group at 3-21 days after injury(P<0.05).Hematoxylin-eosin staining showed that spinal cord injury was greatly reduced in the exosome group compared with the model group.Basso-Beattie-Bresnahan score in the endothelin-1 group was significantly decreased compared with the exosome group(P<0.05).Spinal cord injury was more severe in the endothelin-1 group than that in the exosome group.(2)The expression of endothelin-1 in the model group was significantly increased compared with the sham operation group(P<0.05),and the expression of endothelin-1 in the exosome group was significantly decreased compared with the model group(P<0.05).(3)The blood-spinal cord barrier Evans blue exudate in the exosome group was significantly decreased compared with the model group(P<0.05).The expression levels of the tight junction proteins β-Catenin,Occludin and ZO-1 in the exosome group were increased(P<0.05);the Evans blue exudate in the endothelin-1 group was significantly increased compared with the exosome group(P<0.05).The expression level of tight junction protein was significantly decreased compared with the exosome group(P<0.05).(4)The results show that human umbilical cord mesenchymal cell-derived exosomes protect the permeability of the blood-spinal cord barrier by down-regulating the expression of endothelin-1 and play a role in the repair of spinal cord injury.

Single-cell RNA sequencing reveals the heterogeneity of astrocytes / 中国组织工程研究

BACKGROUND:Astrocytes are the most abundant cells in the central nervous system,and various subsets of astrocytes are heterogeneous,performing a variety of special functions.Single-cell RNA sequencing(scRNA-seq)technology developed in recent years has extended our understanding of astrocyte heterogeneity from the perspective of transcriptome profiling. OBJECTIVE:To summarize the heterogeneity of scRNA-seq technology in different time and space,and pathological states and expand our knowledge of astrocyte heterogeneity on both molecular and functional levels. METHODS:The relevant articles on astrocyte heterogeneity and scRNA-seq were searched on PubMed,Elsevier,and CNKI databases.The search terms were"astrocytes,scRNA-seq,heterogeneity,Alzheimer disease,spinal cord injury,multiple sclerosis"in Chinese and English.Finally,74 articles were selected for viewing after screening according to inclusion criteria. RESULTS AND CONCLUSION:scRNA-seq studies related to the heterogeneity of astrocytes have shown that astrocyte is significantly heterogeneous across four aspects:species,developmental stage,central nervous system region,and pathological state.(1)Unique expression of certain genes occurs in astrocytes of different species,and the discovery of species-specific genes is beneficial for the translation of clinical studies.(2)During astrocyte development,differential gene expression emerged in the cellular subtypes identified at each stage,which further refined the cellular lineage of astrocytes and laid the foundation for the study of astrocyte developmental trajectories and mechanisms.(3)The discovery of differential gene expression allows regional localization of different astrocyte subpopulations and assists in the diagnosis and treatment of neurological diseases.(4)Astrocyte heterogeneity revealed by scRNA-seq can provide specific markers at the time of disease diagnosis and identify potential therapeutic targets.(5)The heterogeneity of astrocytes exists in many aspects,interacts with each other and is complex.The mechanisms of its generation,maintenance and transformation remain unclear.At present,molecular research on the single-cell level is still lacking.Linking transcriptionally defined astrocyte subpopulations to cellular activity,behavior and disease markers in real time remains one of the great challenges in the field.

Tauroursodeoxycholic acid treats spinal cord injury by reducing apoptosis of spinal cord neurons under glucose and oxygen deprivation / 中国组织工程研究

BACKGROUND:Tauroursodeoxycholic acid is a hydrophilic bile acid derivative that has neuroprotective effects in a variety of neurological disease models.However,there are few reports on the effects of tauroursodeoxycholic acid on spinal cord injury. OBJECTIVE:To investigate the effect of tauroursodeoxycholic acid on apoptosis of spinal cord neurons under hypoglycemic and hypoxic conditions,as well as the effect on recovery of motor function in mice after spinal cord injury. METHODS:(1)In vitro experiment:Primary spinal cord neurons were isolated from C57 BL/6 mouse embryos at 13.5 days of gestation.After 72 hours of culture,the cells were divided into three groups.In the normal group,cells were cultured in Neurobasal complete medium that was incubated in a CO2 incubator(5%CO2 + 95%air)for 24 hours.In the oxyglucose-deprived group,sugar-free Neurobasal medium was added and incubated in a triple-gas incubator(94%N2+5%CO2+1%O2)for 12 hours,and then the medium was replaced with Neurobasal complete medium and incubated in a CO2 incubator for 12 hours.In the experimental group,the treatment procedure was approximately the same as that in the oxyglucose-deprived group,except that taurodeoxycholic acid was added along with the sugar-free Neurobasal medium.TUNEL staining was used to detect apoptosis,cell counting kit-8 assay was applied to detect cell activity,and immunofluorescence staining was performed to detect cellular β-microtubule protein expression.(2)Animal experiment:Sixty C57 BL/6 mice were randomly divided into sham-operated group,spinal cord injury group and experimental group,with 20 mice in each group.Animal models of T9-T10 spinal cord injury were established using Allen's percussion method in the spinal cord injury group and the experimental group.Starting from the 1st day after modeling,taurodeoxycholic acid solution was given by gavage in the experimental group and normal saline was given by gavage in the sham-operated and spinal cord injury groups once a day for 14 consecutive days.Spinal cord tissue repair was assessed using behavioral and histological methods. RESULTS AND CONCLUSION:In vitro experiment:TUNEL staining,cell counting kit-8 and immunofluorescence staining showed that compared with the normal group,the number of apoptotic cells was higher(P＜0.01),while cell activity and β-microtubule protein expression were lower in the oxyglucose-deprived group(P＜0.01);compared with the oxyglucose-deprived group,the number of apoptotic cells was lower(P＜0.01),while cell activity and β-microtubule protein expression were higher in the experimental group(P＜0.01).Animal experiment:The Basso-Beattie-Bresnahan scores in the open field test and hind limb footprint experiments showed that the mice in the experimental group had better recovery of walking and motor functions than those in the spinal cord injury group.Hematoxylin-eosin staining showed that significant deformities and cavities were observed at the site of spinal cord injury and the number of nerve cells was significantly reduced in the spinal cord injury group.Compared with the spinal cord injury group,the experimental group showed a significant reduction in the area of spinal cord injury,less spinal cord deformity,fewer cavities,and an increase in the number of nerve cells.Immunofluorescence staining showed that the number of neuronal nucleus-labeled neuronal cells in the spinal cord injury group was less than that in the sham-operated group(P＜0.01),and the number of neuronal nucleus-labeled neuronal cells in the experimental group was higher than that in the spinal cord injury group(P＜0.01).To conclude,tauroursodeoxycholic acid could effectively reduce glucose/oxygen deprivation-induced apoptosis of spinal cord neurons and axonal loss,and promote the recovery of motor function in mice with spinal cord injury.

Efficient strategies for microglia replacement in spinal cord injury models / 中国组织工程研究

BACKGROUND:As the incidence of spinal cord injury increases with the years and axon regeneration after spinal cord injury was very difficult.How to promote the recovery from spinal cord injury and improve the transplantation efficiency of stem cells and other therapeutic cells after spinal cord injury has been the focus of clinical and scientific research. OBJECTIVE:To establish the efficient transplantation and replacement of mouse spinal cord microglia in the spinal cord injury model. METHODS:CX3CR1 creER-/+::LSL-BDNF-/+-tdTomato mice,CX3CR1+/GFP mice,β-actin GFP mice and C57 BL/6J wild-type mice at 8-10 weeks of age were selected.According to the requirements of the experiment,they were randomly divided into six groups.(1)Sham operation group:eight C57 BL/6J wild-type mice were used when only the lamina was removed without injury.(2)Spinal cord contusion injury group:eight C57 BL/6J wild-type mice were used.(3)Spinal cord crush injury group:eight C57 BL/6J wild-type mice were used.(4)Conjoined symbiotic spinal cord strike injury group:β-actin GFP mice with green fluorescent blood were surgically stitched together with C57 BL/6J wild-type mice,using eight β-actin GFP mice and eight C57 BL/6J wild-type mice.(5)Mr BMT-X Ray group(using PLX5622 to eliminate the spinal microglia and bone marrow transplantation with X-ray radiation):Bone marrow cells from four CX3CR1 creER-/+::LSL-BDNF-/+-tdTomato mice were extracted and transplanted into eight C57 BL/6J wild-type mice for spinal cord injury modeling.(6)Mr BMT-Busulfan group(using PLX5622 to eliminate the spinal microglia and bone marrow transplantation with Busulfan):Bone marrow cells from four CX3CR1+/GFP mice were transplanted into eight C57 BL/6J wild-type mice.The percentage of cell transplantation replacement in this group was observed,and the spinal cord injury model was not established in this group.The sham operation group,spinal cord contusion injury group and spinal cord crush injury group were sampled by perfusion on day 14 after spinal cord injury.The conjoined symbiotic spinal cord strike injury group was sampled by perfusion on day 7 after spinal cord injury.Mr BMT-X Ray group was sampled by perfusion on day 28 after spinal cord injury.Mr BMT-Busulfan group was sampled by perfusion on day 28 after transplantation.The sampling site was a 1.2 cm long spinal cord with the T10 segment as the center.In the Mr BMT-X Ray group and Mr BMT-Busulfan group,additional mouse brain tissue was retained to see if it would lead to brain transplantation and replacement.The number and proportion of transplanted and replaced cells in the damaged area were measured using transgenic mice,symbiosis and immunofluorescence. RESULTS AND CONCLUSION:Compared with the traditional peripheral blood transplantation(9.8%)of mice in the conjoined symbiotic spinal cord strike injury group,the new transplantation methods,Mr BMT-X Ray and Mr BMT-Busulfan,could greatly improve the proportion of spinal microglia transplantation and replacement,which could reach 84.8%and 95.6%,respectively.The difference was significant(P<0.05).The results showed that Mr BMT-X Ray and Mr BMT-Busulfan could achieve efficient replacement of spinal microglia cells,and could improve the problems of low cell transplantation efficiency,few survival numbers and unclear differentiation of the traditional cell transplantation methods.In addition,Mr BMT-X Ray can only replace the microglia in the spinal cord,while Mr BMT-Busulfan could avoid brain inflammation and injury caused by X-ray radiation transplantation.

Riluzole interferes with the activation of NLRP3 inflammasome in microglia of rats with spinal cord injury / 中国组织工程研究

BACKGROUND:Previous animal studies have shown that riluzole can inhibit neuroinflammatory response after spinal cord injury and promote functional recovery in injured rats,but the study on whether it can regulate the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome in the acute stage is lacking. OBJECTIVE:To observe whether riluzole can reduce microglial pyroptosis and promote functional recovery after spinal cord injury by modulating NLRP3 inflammasome through animal experiments,histological experiments and molecular biology experiments. METHODS:Female SD rats were divided into sham operation,model and riluzole groups,with 12 rats in each group.In addition to the sham operation group,T10 spinal cord injury was conducted in rats.The model group was treated with intraperitoneal administration of riluzole with solvent cyclodextrin.The riluzole group was treated with a 4 mg/kg dose of riluzole injection.The effect of riluzole on motor function recovery was assessed using the BBB score and inclined plane test.The recovery of sensory-evoked potential and motor-evoked potential was measured by electrophysiology.Hematoxylin-eosin staining was used to evaluate spinal cord tissue repair.The regulatory effects of riluzole on NLRP3,Caspase-1 and gasdermin D protein expression in spinal cord tissues were detected by western blot assay.ELISA was utilized to detect the expression levels of inflammatory factors interleukin-1β and interleukin-18.The effects of riluzole on the expression of NLRP3,Caspase-1,gasdermin D and interleukin-1β in microglial cells of the injured spinal cord were determined by immunofluorescence staining. RESULTS AND CONCLUSION:(1)At 35 days after spinal cord injury,BBB score and inclined plane test score in the riluzole group were higher than those in the model group(P<0.05).(2)At 3 days after spinal cord injury,the protein expressions of NLRP3,cleaved Caspase-1,gasdermin D-N(N-terminal domain),interleukin-1β,and interleukin-18 in the spinal cord homogenate of the riluzole group were significantly lower than those of the model group(P<0.05).(3)At 3 days after spinal cord injury,the fluorescence intensity of NLRP3,Caspase-1,gasdermin D and interleukin-1β in the riluzole group was significantly lower than that in the model group(P<0.05).(4)At day 35 after spinal cord injury,hematoxylin-eosin staining showed that the area of spinal cord injury in the riluzole group was smaller than that in the model group.Electrophysiological tests showed that the latency periods of sensory-evoked potential and motor-evoked potential in the riluzole group were shorter than those in the model group,and the latency period of wave amplitude in the riluzole group was higher than that in the model group.(5)These results suggest that riluzole can promote the repair of injured spinal cord tissue,promote the repair of nerve conduction function,and further promote the recovery of motor function in rats with spinal cord injury,which may be achieved through the regulation of NLRP3 inflammasome and the reduction of microglial pyroptosis.

Effects of Periplaneta americana powder on motor function and autophagic protein Beclin-1 in rats undergoing spinal cord hemisection / 中国组织工程研究

BACKGROUND:Spinal cord injury involves mechanisms such as oxidative stress,inflammation,apoptosis and autophagy.Activation of autophagy can improve neuromotor function after spinal cord injury and play a protective role in the spinal cord. OBJECTIVE:To investigate the effects of Periplaneta americana powder on hindlimb motor function and the autophagy protein Beclin-1 in the injured site of rats after spinal cord hemisection. METHODS:Thirty Sprague-Dawley rats,6-8 weeks of age,were randomly divided into three groups(n=10 per group).In the sham-operated group,the lamina was just opened to exposure the spinal cord followed by suturing.Normal saline group and Periplaneta americana powder group both underwent left hemisection of the spinal cord to prepare animal models of spinal cord hemisection.The normal saline group was continuously gavaged with normal saline for 14 days,and the Periplaneta americana powder group was continuously gavaged with Periplaneta americana powder for 14 days.The Basso Beattie Bresnahan scale score was performed at the 6th hour,1st day,3rd day,7th day and 14th day after operation to observe the hindlimb motor function.After 14 days of administration,the rats were sacrificed and sampled.Immunohistochemistry,western blot and immunofluorescence were used to detect the expression of Beclin-1 in the injured site of the spinal cord after hemisection. RESULTS AND CONCLUSION:After operation,the Basso Beattie Bresnahan scale scores were gradually increased in the normal saline group and Periplaneta americana powder group.Compared with the sham-operated group,the Basso Beattie Bresnahan scale scores were significantly reduced in the normal saline group and Periplaneta americana powder group at the 6th hour,1st day,3rd day,7th day and 14th day after operation(P<0.05).The Basso Beattie Bresnahan scale scores in the Periplaneta americana powder group were significantly higher than those in the normal saline group at the 7th and 14th days after operation(P<0.05).Immunohistochemical staining showed that Beclin-1 was weakly positive in the sham-operated group,mainly expressed in the cytoplasm;in the normal saline group,Beclin-1 was mainly expressed in the cytoplasm and partially expressed in the nuclear membrane;in the Periplaneta americana powder group,Beclin-1 was mainly expressed in the cytoplasm and partially expressed in the nuclear membrane.The proportion of Beclin-1 positive cells was higher in the normal saline and Periplaneta americana powder groups than in the sham-operated group(P<0.05),while the proportion of Beclin-1 positive cells was higher in the Periplaneta americana powder group than in the normal saline group(P<0.05).Western blot assay and immunofluorescence staining showed that the Beclin-1 protein expression was higher in the normal saline and Periplaneta americana powder groups than in the sham-operated group(P<0.05),and moreover,the Beclin-1 protein expression was higher in the Periplaneta americana powder group than in the normal saline group(P<0.05).To conclude,Periplaneta americana powder could improve the hindlimb motor function of rats with spinal cord hemisection injury,and the mechanism may be that polysaccharides in the Periplaneta americana powder increase the expression of Beclin-1.

Characterization and repair effect of supramolecular conducting hydrogel carrying ligustrazine on spinal cord injury in rats / 中国组织工程研究

BACKGROUND:Based on the concept of the combination of medicine and industry and the advantages of traditional Chinese medicine treatment,the construction of a new composite material loaded with the effective active ingredient of traditional Chinese medicine is a hot research spot in the repair of spinal cord injury,and is expected to become an effective means to solve this problem. OBJECTIVE:To observe the effect of supramolecular conducting hydrogel carrying ligustrazine in repairing spinal cord injury in rats. METHODS:The supramolecular conducting hydrogel carrying ligustrazine was prepared and its microstructure,conductivity,rheology,swelling rate and in vitro release performance were characterized.45 SD rats were divided into 3 groups by random number table method,with 15 rats in each group:no spinal cord injury in the sham operation group;spinal cord injury model was established in the model group;and supramolecular conducting hydrogel carrying ligustrazine was injected into the spinal cord injury area after model establishment in hydrogel group.BBB score was used to evaluate the recovery of hind limb motor function of each group before and 1,7,14,21 and 28 days after modeling,respectively.28 days after the model establishment,the spinal cord tissues were collected and analyzed by hematoxylin-eosin staining,immunohistochemical staining and western blot assay. RESULTS AND CONCLUSION:(1)Under scanning electron microscopy,the supramolecular conducting hydrogel with ligustrazine displayed a three-dimensional micrometer-scale porous network structure with high porosity and a pore size of approximately 100 μm.The conductivity of the hydrogel was 7.66 S/m;the swelling rate was 3 764.42%,and it had certain mechanical stability and injection property.In vitro sustained release experiments demonstrated that the supramolecular conducting hydrogel with ligustrazine sustainably released ligustrazine for more than 800 hours.With the extension of time,the cumulative release of ligustrazine exhibited an increasing trend.(2)With the extension of modeling time,the hind limb motor function gradually recovered in the model group and the hydrogel group,and the hind limb motor function of the hydrogel group was better than that of the model group on 14,21,and 28 days after modeling(P<0.05).Hematoxylin-eosin staining demonstrated that the spinal cord tissue of the model group had cavities and a large number of inflammatory cells could be seen at the stump.In the hydrogel group,some inflammatory cells were infiltrated in the injured area of the spinal cord;the void area of the injured area was reduced;neuron cells appeared in the junction area,and the tissue arrangement was relatively neat.Immunohistochemical staining and western blot assay exhibited that the expression of tumor necrosis factor α and interleukin-6 protein in the rat spinal cord of the hydrogel group was lower than that in the model group(P<0.05),and the expression of neuronal nuclear antigen protein was higher than that in the model group(P<0.05).(3)These findings confirm that the supramolecular conducting hydrogel carrying ligustrazine can promote the repair of spinal cord injury.

Repetitive magnetic stimulation of S3 nerve root and M1 area for treating urinary retention after spinal cord injury / 中国组织工程研究

BACKGROUND:Repetitive magnetic stimulation of either S3 nerve root or M1 area can improve the urination function of patients with urinary retention after spinal cord injury,but there are few reports on the repetitive magnetic stimulation of both sites in patients with urinary retention after spinal cord injury. OBJECTIVE:To observe the effect of repetitive magnetic stimulation of both S3 nerve root and M1 area on urinary retention after spinal cord injury. METHODS:Forty patients with urinary retention after spinal cord injury were enrolled and were randomly divided into two groups(n=20 per group):group A(repetitive magnetic stimulation in both S3 nerve root and M1 area)and group B(repetitive magnetic stimulation in the S3 nerve root and sham stimulation in the M1 area).Patients in both groups were given 4-week repetitive magnetic stimulation based on conventional bladder function intervention.The stimulation time and duration of treatment were same in both groups,with a treatment time of 21 minutes daily,5 days per week,for 4 weeks in total.The urination diary and urodynamics were compared between two groups. RESULTS AND CONCLUSION:Before treatment,there were no statistically significant differences in the average daily catheterization times,average daily catheterization volume,average single urinary volume,urinary storage period(maximum bladder volume,bladder pressure),and urinary voiding period(detrusor pressure,residual urine volume)between the two groups(P>0.05).After 4 weeks of treatment,the average daily catheterization times in group A were lower than before treatment(P<0.05),while the average single urination volume in group A was higher than that before treatment(P<0.05);and the average daily catheterization times in group B were lower than before treatment(P<0.05).After 4 weeks of treatment,the average daily catheterization times in group A were lower than those in group B,and the average single urination volume was higher than that in group B(P<0.05).After 4 weeks of treatment,the maximum bladder volume and detrusor pressure during urination were increased in both groups compared with before treatment(P<0.05),while the bladder pressure and residual urine volume at the maximum volume of the two groups were decreased compared with those before treatment(P<0.05).Compared with group B,the maximum bladder volume and detrusor pressure during urination were higher in group A,while the bladder pressure and residual urine volume at maximum volume were lower in group A(P<0.05).To conclude,two treatments can both improve the urination function of patients with urinary retention after spinal cord injury,and repetitive magnetic stimulation of both S3 nerve root and M1 area is superior to repetitive magnetic stimulation of S3 nerve root alone.Repetitive magnetic stimulation of both S3 nerve root and M1 area can effectively improve the urination function of patients with urinary retention after spinal cord injury.

Regulatory mechanisms and therapeutic strategies for pyroptosis after spinal cord injury / 中国组织工程研究

BACKGROUND:Cell death and neuroinflammation are two important targets in the treatment of spinal cord injury.Pyroptosis is a programmed cell death closely related to neuroinflammation and targeted inhibition of pyroptosis after spinal cord injury is a promising therapeutic strategy. OBJECTIVE:To summarize the molecular mechanism,positive and negative regulatory factors and therapeutic strategies of pyroptosis in spinal cord injury. METHODS:The search terms were"spinal cord injury,pyroptosis,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),Caspase,Gasdermin D(GSDMD),IL-1β,IL-18"and 93 English literatures included in PubMed and Web of Science were finally selected for review. RESULTS AND CONCLUSION:As a newly discovered programmed cell death,pyroptosis has been shown to play an important role in the secondary injury stage after spinal cord injury.Among the regulatory factors of pyroptosis after spinal cord injury,CD73,NRF2,GDF-11,dopamine,FANCC and miR-423-5P could inhibit pyroptosis,while TLR4 and Aopps could promote pyroptosis.In terms of treatment,the active ingredients of traditional Chinese medicine(paeonol,tripterine,betulinic acid,piperine,kaempferol,and camptothecin),exosomes of various cell origins,and some drugs(metformin,topotecan,lithium,zinc,and carbon monoxide-releasing molecule 3)can effectively inhibit pyroptosis and reduce secondary spinal cord injury,but the toxicity and specific dose of these drugs need to be further studied.The specific molecular mechanism by which pyroptosis aggravates spinal cord injury is still poorly understood.The role of non-classical pathways and other inflammasomes is worth further exploration.At present,the research on pyroptosis after spinal cord injury only stays at the animal experiment stage.There are no related clinical studies and no approved targeted therapeutic drugs.(6)The application of pyroptosis after spinal cord injury has great potential,and its specific regulatory mechanism should be further studied in the future to provide a new target for the treatment of spinal cord injury.

Application and prospect of reconstructing bladder micturition reflex in neurogenic bladder after spinal cord injury / 中国组织工程研究

BACKGROUND:The dysfunction of bladder function caused by spinal cord injury is a difficult point in clinical treatment and a hot spot in research.Repairing the injured spinal cord and remodeling the bladder micturition reflex pathway are the fundamental treatment methods. OBJECTIVE:To summarize the reconstruction of the bladder innervation pathway after spinal cord transection injury and its related influencing factors. METHODS:The relevant literature concerning the reconstruction of bladder micturition reflex,neurogenic bladder and urinary reflex and spinal cord repair was retrieved on CNKI,WanFang Data,PubMed and Web of Science.Chinese and English search terms were"neurogenic bladder;spinal cord injury;micturition reflex;spinal cord repair". RESULTS AND CONCLUSION:In the process of reconstructing the bladder micturition reflex,there are many factors involved,including the repair and reconstruction of the injured spinal cord,the remodeling of micturition center,the changes of bladder tissue and substances and hormones in and out of the body.In this process,there are mainly the following problems:(1)As a complex process,there are many sites involved in the reconstruction of the micturition reflex,so the main sites of action can be selected for in-depth study,so as to break through the doubts existing in the reconstruction of the micturition reflex pathway.(2)The mechanism of the normal micturition reflex is complex.After spinal cord transection injury,whether the central nucleus mass controlling or participating in the micturition reflex is compensated and the corresponding compensatory mechanism needs to be further investigated.(3)Information communication between the center and the bladder is interrupted after spinal cord transection injury.Whether there is a direct information connection between the center and the bladder remains to be further investigated.(4)The relationship between reconstructing micturition reflex and body fluid after spinal cord transection injury needs further study.In the reconstruction of the bladder micturition reflex,the key treatment is to promote spinal cord repair,nerve reflex reconstruction,substance metabolism and bladder tissue structure adjustment through intervention.Chinese medicine and Western medicine have their methods.

Bone marrow mesenchymal stem cell exosomes combined with epigallocatechin-3-gallate in treatment of spinal cord ischemia/reperfusion injury in rats / 中国组织工程研究

BACKGROUND:Studies have exhibited that inhibiting apoptosis caused by endoplasmic reticulum stress can save part of nerve function.Epigallocatechin-3-gallate can inhibit endoplasmic reticulum stress,but it has poor bioavailability and is difficult to penetrate the blood-brain barrier.In combination with exosomes targeting spinal cord repair and high-potency drug loading,theoretically,the combination of the two can play a greater role in spinal cord protection. OBJECTIVE:To investigate the effects of epigallocatechin-3-gallate combined with bone marrow mesenchymal stem cell exosomes on endoplasmic reticulum stress and neurological function in rats with spinal cord ischemia/reperfusion injury. METHODS:Fifty SD male rats were randomly divided into sham surgery group,model group,epigallocatechin-3-gallate group,exosome group,and combined treatment group,with 10 rats in each group.The spinal cord ischemia/reperfusion injury model was made in the other four groups except for the sham surgery group.Local injection of physiological saline,exosomes,epigallocatechin-3-gallate,epigallocatechin-3-gallate + bone marrow mesenchymal stem cell exosomes was performed 2 hours after surgery through a caudal vein.Neurological function scores were performed on 7,14 and 28 days after spinal cord injury.14 days after spinal cord injury,hematoxylin-eosin staining,Nissl staining,and immunofluorescence staining of endoplasmic reticulum stress markers such as ATF6 and GADD153 were performed in the spinal cord tissues. RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,neurological function scores of the model group,exosome group,epigallocatechin-3-gallate group and combined treatment group all decreased to different degrees.The neurological function score of combined treatment group was better than that of the epigallocatechin-3-gallate group,exosome group and model group 14 days after surgery(P<0.05).The neurological function score of the combined treatment group was better than that of the model group and epigallocatechin-3-gallate group 28 days after surgery(P<0.05).(2)Hematoxylin-eosin staining and Nissl staining displayed that the number of neurons in the model group decreased,with a large number of cavity necrosis and scar hyperplasia in the spinal cord injury area.The number of neurons and peripheral cavity necrosis improved to varying degrees in the epigallocatechin-3-gallate group,exosome group,and combined treatment group,with the most significant improvement in the combined treatment group.(3)The expression of endoplasmic reticulum stress-related proteins ATF6 and GADD153:14 days postoperatively,the expression of GADD153 in the combined treatment group was lower than that in the model group and epigallocatechin-3-gallate group(P<0.05),and the expression of ATF6 in the combined treatment group was lower than that in the model group,exosome group,and epigallocatechin-3-gallate group(P<0.05).(4)These findings confirm that epigallocatechin-3-gallate combined with bone marrow mesenchymal stem cell exosome can enhance the neurological function in rats with spinal cord ischemia/reperfusionn injury,which may be associated with the inhibition of the expression of endoplasmic reticulum stress-related proteins ATF6 and GADD153.

Strategies and advance on stem cell transplantation for repair of spinal cord injury / 中国组织工程研究

BACKGROUND:Spinal cord injury not only causes serious physical and psychological injuries to patients but also brings a heavy economic burden to society.Spinal cord injury is initially triggered by mechanical trauma,followed by secondary injuries,and as the disease progresses,a glial scar develops. OBJECTIVE:To summarize the pathological process of spinal cord injury and strategies for stem cell transplantation to repair spinal cord injury,aiming to provide the best protocol for treating spinal cord injury. METHODS:Computer search was used to search PubMed and CNKI databases.Chinese search terms were"stem cell transplantation,spinal cord injury".English search terms were"stem cell,spinal cord injury,spinal cord,mesenchymal stem cells,neural stem cells,pathophysiology,clinical trial,primary injury,secondary injury".The literature was screened according to the inclusion and exclusion criteria.Finally,91 articles were included for review analysis. RESULTS AND CONCLUSION:(1)The strategies for repairing spinal cord injury through stem cell transplantation can be divided into exogenous stem cell transplantation and endogenous stem cell transplantation.The exogenous stem cell transplantation strategy for the treatment of spinal cord injury is divided into four kinds:injecting stem cells into the site of injury;transplantation of biomaterials loaded with stem cells;fetal tissue transplantation;transplantation of engineered neural network tissue or spinal cord-like tissue.(2)Compared with a single treatment method,combination therapy can more effectively promote nerve regeneration and spinal cord function recovery.(3)Microenvironment regulating the injury site,magnetic stimulation,electrical stimulation,epidural oscillating electric field stimulation,transcription factor overexpression and rehabilitation therapy can be combined with stem cell transplantation for combination therapy,thereby promoting the recovery of spinal cord function.

miR-146a-3p regulates astrocyte proliferation,migration and apoptosis by inhibiting insulin-like growth factor 1 expression / 中国组织工程研究

BACKGROUND:The alteration of miR-146a-3p level is a common event in the pathogenesis of most neurological diseases,and the specific mechanism of miR-146a-3p regulation of astrocytes has not been studied. OBJECTIVE:To verify that miR-146a-3p regulates astrocyte proliferation,migration and apoptosis through insulin-like growth factor 1. METHODS:12 SD rats were divided into a sham operation group and a spinal cord injury group,with six rats in each group.RNA sequencing analysis was performed on the spinal cord tissues of all groups 2 weeks after surgery to screen out the differential genes(log2FC>2),and to select spinal cord injury-related genes(Score>20)in the Genecards database,and then to predict the target genes of miR-146a-3p by Targetscan.The intersection of three gene sets was obtained to screen out insulin-like growth factor 1 as one of the important target genes.qPCR,western blot assay and immunohistochemistry were performed to analyze the expression level of insulin-like growth factor 1 in spinal cord tissues.The primary astrocytes were divided into NC group,NC-mimics group and miR-146a-3p mimics group.Annexin-V/PI staining was used to detect cell apoptosis.CCK-8 assay was used to detect cell proliferation.Transwell assay was used to detect cell migration ability. RESULTS AND CONCLUSION:The expression of miR-146a-3p in the spinal cord tissue of the spinal cord injury group was lower than that of the sham operation group(P<0.05).The expression of insulin-like growth factor 1 in the spinal cord tissue of the spinal cord injury group was higher than that of the sham operation group(P<0.05).Compared with the NC group and NC-mimics group,the apoptotic rate of astrocytes was increased(P<0.01);the proliferation of astrocytes was decreased(P<0.01)and the number of migration was decreased(P<0.01)in the miR-146a-3p mimics group.To conclude,the expression of miR-146a-3p decreased and the expression of insulin-like growth factor 1 increased in spinal cord tissue after spinal cord injury.miR-146a-3p targeted regulation of insulin-like growth factor 1 in astrocytes,inhibited the proliferation and migration of astrocytes and promoted their apoptosis.