Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Effect of cardiac rehabilitation care after coronary intervention on cardiac function recovery and negative mood in patients with myocardial infarction

BACKGROUND Cardiovascular disease,particularly myocardial infarction(MI)profound impact on patients'quality of life and places a substantial burden on the healthcare and economy systems.Developments in medical technology have led to the emer-gence of coronary intervention as an essential method for treating MI.AIM To assess the effects of cardiac rehabilitation care on cardiac function recovery and negative emotions in MI after coronary intervention.METHODS This study included a total of 180 patients with MI during the period from June 2022 to July 2023.Selected patients were divided into two groups:An observation group,which receiving cardiac rehabilitation care;a control group,which re-ceiving conventional care.By comparing multiple observation indicators such as cardiac function indicators,blood pressure,exercise tolerance,occurrence of adverse cardiac events,and negative emotion scores between the two groups of patients.All the data were analyzed and compared between two groups.RESULTS There were 44 males and 46 females in the observation group with an average age of 36.26±9.88 yr;there were 43 males and 47 females in the control group,with an average age of 40.87±10.5 yr.After receiving the appropriate postoperative nursing measures,the results of the observation group showed significant improvement in several indicators compared with the control group.Indicators of cardiac function,such as left ventricular end-diastolic internal diameter and left ventricular ejection fraction were significantly better in the observation group than in the control group(P<0.05).Exercise endurance assessment showed that the 6-minute walking test distance was significantly increased in the patients of the observation group(P<0.01).In addition,the incidence of adverse cardiac events was significantly lower in the observation group,and negative mood scores were significantly reduced(P<0.05).CONCLUSION Cardiac rehabilitation care after coronary intervention has a significant positive impact on functional recovery.This emphasizes the importance of cardiac rehabilitation care to improve patient recovery.

Clinical observation of gastrointestinal function recovery in patients after hepatobiliary surgery

BACKGROUND The liver is an important metabolic and digestive organ in the human body,ca-pable of producing bile,clotting factors,and vitamins.AIM To investigate the recovery of gastrointestinal function in patients after hepato-biliary surgery and identify effective rehabilitation measures.METHODS A total of 200 patients who underwent hepatobiliary surgery in our hospital in 2022 were selected as the study subjects.They were divided into a control group and a study group based on the extent of the surgery,with 100 patients in each group.The control group received routine treatment,while the study group re-ceived targeted interventions,including early enteral nutrition support,drinking water before gas discharge,and large bowel enema,to promote postoperative gastrointestinal function recovery.The recovery of gastrointestinal function was compared between the two groups.RESULTS Compared with the control group,patients in the study group had better recovery of bowel sounds and less accumulation of fluids in the liver bed and gallbladder fossa(P<0.05).They also had shorter time to gas discharge and first meal(P<0.05),higher overall effective rate of gastrointestinal function recovery(P<0.05),and lower incidence of postoperative complications(P<0.05).CONCLUSION Targeted nursing interventions(early nutritional support,drinking water before gas discharge,and enema)can effectively promote gastrointestinal function recovery in patients undergoing hepatobiliary surgery and reduce the incidence of complications,which is worthy of promotion.

Influences of Horticultural Therapy and Functional Recovery Training at a Day-Care Center for the Elderly and Text Mining of Care Records by AI

Background: In Japan, due to the COVID-19 pandemic, various behavioral restrictions were implemented from March 2020, resulting in an increased number of elderly people with reduced participation in care and rehabilitation. As a result, the decline in motor and cognitive functions became more pronounced. Purpose: The study examined how activities combining passive horticultural therapy, which is always introduced, with active functional recovery training, which is used in the functional recovery training of patients with hemiplegia, influence the behavior of elder people using the facility. Methods: 36 elder people with care need 1 or 2 who regularly used the day-care facilities after the pandemic ended and who agreed to participate in the study was included. The assessment data were every three months from December 2021 to December 2023 after the COVID-19 pandemic, the MMSE and Moca-J, TMIG-Index, and GDS15. AI-based text mining was used to compare changes in visit reports before and after the introduction of the Posture Chart and Red Code, and the relationship between the language used. Results: The results of MMSE and Moca-J were both significantly higher in Group B and C than in Group A. TIMG assessment, was significantly higher in Group B and C than in Group A, and Group C was significantly higher than Group B. The GDS, an assessment of depression in old age, tended to be significantly higher in Group A than in Groups B and C. In the “Co-Occurrence Network Analysis” shown after the introduction of the latest functional recovery training equipment such as the Red Cord, its results showed a high association between the words Bathing and CARE and words such as POSTURE, Red-Code, and AI, App, which are used in functional training and rehabilitation, and their analysis. Conclusion: At day-care facilities specializing in functional recovery training and rehabilitation, a combination of horticultural therapy and the latest functional training equipment found to help maintain the physical and mental health of elderly people certified as requiring nursing care. Since this is a short-term study following behavioral restrictions, long-term research should continue to study the effects of adding functional training, handled by rehabilitation professionals, to horticultural therapy.

The Effect of Case Management Model on the Application of Pancreatic Cancer Surgery Patients and the Recovery of Gastrointestinal Function

Objective:To evaluate the effect of the case management model on patients operated for pancreatic cancer.Methods:90 pancreatic cancer surgery patients admitted to the hospital between January 2022 and June 2023 were selected and grouped by randomized numerical table.For 45 cases in the observation group,case management mode was adopted,and for 45 cases in the intervention group,conventional nursing care was chosen to compare the indexes of gastrointestinal function recovery.Results:The recovery time of all gastrointestinal functions of the observation group was shorter than that of the intervention group;after nursing,the psychological state score of the observation group was lower than that of the intervention group,the self-efficacy score was higher than that of the intervention group and the rate of complications was lower than that of the intervention group(P<0.05).Conclusion:The case management model can promote the recovery of gastrointestinal function in patients with pancreatic cancer surgery and its nursing feasibility is high.

miR-181b promotes angiogenesis and neurological function recovery after ischemic stroke

Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.

A hyaluronic acid granular hydrogel nerve guidance conduit promotes regeneration and functional recovery of injured sciatic nerves in rats

A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration.However,in vivo experiments have not been conducted.In this study,we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap.The Basso,Beattie,and Bresnahan locomotor rating scale,sciatic nerve compound muscle action potential recording,Fluoro-Gold retrograde tracing,growth related protein 43/S100 immunofluorescence staining,transmission electron microscopy,gastrocnemius muscle dry/wet weight ratio,and Masson’s trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath,and recovery of the electrophysiological function and motor function as autologous nerve transplantation.The conduit results were superior to those of a bulk hydrogel or silicone tube transplant.These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve.The nerve conduits have the potential as a material for repairing peripheral nerve defects.

Multidisciplinary approach toward enhanced recovery after surgery for total knee arthroplasty improves outcomes

Knee osteoarthritis is a degenerative disorder of the knee,which leads to joint pain,stiffness,and inactivity and significantly affects the quality of life.With an increased prevalence of obesity and greater life expectancies,total knee arthroplasty(TKA)is now one of the major arthroplasty surgeries performed for knee osteoarthritis.When enhanced recovery after surgery(ERAS)was introduced in TKA,clinical outcomes were enhanced and the economic burden on the healthcare system was reduced.ERAS is an evidence-based scientific protocol aimed at ameliorating the surgical stress response.ERAS aims to enhance the recovery phase,which encompasses multidisciplinary strategies at every step of perioperative care,including the rehabilitation phase.Implementation of ERAS in TKA aids in reducing the length of hospital stay,improving pain management,reducing perioperative complications,and enhancing patient satisfaction.Multidisciplinary collaboration,integrating the expertise of anesthesiologists,orthopedic surgeons,nursing personnel,and other healthcare professionals,is the cornerstone of ERAS in patients undergoing TKA.

Functional recovery and muscle atrophy in pre-clinical models of peripheral nerve transection and gap-grafting in mice:effects of 4-aminopyridine

We recently demonstrated a repurposing beneficial effect of 4-aminopyridine(4-AP),a potassium channel blocker,on functional recove ry and muscle atrophy after sciatic nerve crush injury in rodents.However,this effect of 4-AP is unknown in nerve transection,gap,and grafting models.To evaluate and compare the functional recovery,nerve morphology,and muscle atrophy,we used a novel stepwise nerve transection with gluing(STG),as well as 7-mm irreparable nerve gap(G-7/0)and 7-mm isografting in 5-mm gap(G-5/7)models in the absence and presence of 4-AP treatment.Following surgery,sciatic functional index was determined wee kly to evaluate the direct in vivo global motor functional recovery.After 12 weeks,nerves were processed for whole-mount immunofluorescence imaging,and tibialis anterior muscles were harvested for wet weight and quantitative histomorphological analyses for muscle fiber crosssectional area and minimal Feret's diameter.Average post-injury sciatic functional index values in STG and G-5/7 models were significantly greater than those in the G-7/0 model.4-AP did not affect the sciatic functional index recovery in any model.Compared to STG,nerve imaging revealed more misdirected axons and distorted nerve architecture with isografting.While muscle weight,cross-sectional area,and minimal Feret's diameter were significantly smaller in G-7/0 model compared with STG and G-5/7,4-AP treatment significantly increased right TA muscle mass,cross-sectional area,and minimal Feret's diameter in G-7/0 model.These findings demonstrate that functional recovery and muscle atrophy after peripheral nerve injury are directly related to the intervening nerve gap,and 4-AP exerts diffe rential effects on functional recove ry and muscle atrophy.

Effect of non-pharmacological treatment on the full recovery of social functioning in patients with attention deficit hyperactivity disorder

BACKGROUND Long-term treatment of attention deficit/hyperactivity disorder(ADHD)is associated with adverse events,such as nausea and vomiting,dizziness,and sleep disturbances,and poor maintenance of late ADHD medication compromises treatment outcomes and prolongs the recovery of patients’social functioning.AIM To evaluate the effect of non-pharmacological treatment on the full recovery of social functioning in patients with ADHD.METHODS A total of 90 patients diagnosed with ADHD between May 2019 and August 2020 were included in the study and randomly assigned to either the pharmacological group(methylphenidate hydrochloride and tomoxetine hydrochloride)or the non-pharmacological group(parental training,behavior modification,sensory integration therapy,and sand tray therapy),with 45 cases in each group.Outcome measures included treatment compliance,Swanson,Nolan,and Pelham,Version IV(SNAP-IV)scores,Conners Parent Symptom Questionnaire(PSQ)scores,and Weiss Functional Impairment Rating Scale(WFIRS)scores.RESULTS The non-pharmacological interventions resulted in significantly higher compliance in patients(95.56%)compared with medication(71.11%)(P<0.05).However,no significant differences in SNAP-IV and PSQ scores,in addition to the learning/school,social activities,and adventure activities of the WFIRS scores were observed between the two groups(P>0.05).Patients with non-pharmacological interventions showed higher WFIRS scores for family,daily life skills,and self-concept than those in the pharmacological group(P<0.05).CONCLUSION Non-pharmacological interventions,in contrast to the potential risks of adverse events after longterm medication,improve patient treatment compliance,alleviate patients’behavioral symptoms of attention,impulsivity,and hyperactivity,and improve their cognitive ability,thereby improving family relationships and patient self-evaluation.

Enhanced recovery after surgery-based nursing in older patients with postoperative intestinal obstruction after gastric cancer surgery:A retrospective study

BACKGROUND Gastric cancer-related morbidity and mortality rates are high in China.Patients who have undergone gastric cancer surgery should receive six cycles of chemotherapy according to their condition.During this period,intestinal obstruction is likely to occur.Electrolyte balance disorders,peritonitis,intestinal necrosis,and even hypovolemic shock and septic shock can seriously affect the physical and mental recovery of patients and threaten their health and quality of life(QoL).AIM To quantitatively explore the effects of enhanced recovery after surgery(ERAS)-based nursing on anxiety,depression,and QoL of elderly patients with postoperative intestinal obstruction after gastric cancer.METHODS The clinical data of 129 older patients with intestinal obstruction after gastric cancer surgery who were treated and cared for in our hospital between January 2019 and December 2021 were examined retrospectively.Nine patients dropped out because of transfer,relocation,or death.According to the order of admissions,the patients were categorized into either a comparison group or an observation group according to the random number table,with 60 cases in each group.RESULTS After nursing care,the observation group required significantly less time to eat for the first time,recover bowel sounds,pass gas,and defecate than the comparison group(P<0.05).No significant difference was noted in nutrition-related indicators between the two groups before care.Before care,the Symptom Check List-90 scores between the two groups were comparable,whereas anxiety,depression,paranoia,fear,hostility,obsession,somatization,interpersonal sensitivity,and psychotic scores were significantly lower in the observation group after care(P<0.05).The QoL scores between the two groups before care did not differ significantly.After care,the physical,social,physiological,and emotional function scores;mental health score;vitality score;and general health score were significantly higher in the observation group,whereas the somatic pain score was significantly lower in the observation group(P<0.05).CONCLUSION ERAS-based nursing combined with conventional nursing interventions can effectively improve patient’s QoL,negative emotions,and nutritional status;accelerate the time to first ventilation;and promote intestinal function recovery in elderly patients with postoperative intestinal obstruction after gastric cancer surgery.

Changes in postoperative depression and anxiety and their relationship with recovery from femoral head necrosis:A longitudinal study

BACKGROUND Femoral head necrosis(FHN)can significantly affect patients'psychological well-being and functional outcomes.However,the long-term relationship between postoperative depression,anxiety,and functional recovery in patients with FHN remains unclear.AIM To investigate the dynamic changes in postoperative depression and anxiety and their relationship with functional recovery in patients with FHN for 3 years.METHODS Ninety-three patients with FHN who underwent surgical treatment in March 2020 to 2023 were enrolled in this longitudinal study.Depression and anxiety status were assessed using the hospital anxiety and depression scale(HADS)at baseline,6 months,1,2,and 3 years postoperatively.Functional recovery was evaluated using the Harris hip score(HHS).The dynamic changes in HADS and HHS were analyzed using repeated measures ANOVA;the relationship between depre-ssion/anxiety status and functional recovery was examined using Pearson’s correlation analysis.RESULTS The mean HADS-depression(HADS-D)and HADS-anxiety(HADS-A)scores significantly improved over time(P<0.001).The prevalence of depression and anxiety decreased from 36.6%and 41.9%at baseline to 10.8%and 12.9%,respectively,at 3 years postoperatively.The mean HHS increased sig-nificantly from 52.3±10.5 at baseline to 88.1±7.2 at 3 years postoperatively(P<0.001).Significant negative correl-ations were found between HADS-D/HADS-A scores and HHS at all time points(P<0.05).CONCLUSION The severity of depression and anxiety negatively correlated with functional recovery,highlighting the importance of psychological interventions in the management of patients with FHN.

Effects of oral probiotics on inflammation and intestinal function in adult patients after appendectomy:Randomized controlled trial

BACKGROUND Appendectomy is an acute abdominal surgery that is often accompanied by severe abdominal inflammation.Oral probiotics are one of the postoperative treatments for rapid rehabilitation.However,there is a lack of prospective studies on this topic after appendectomy.AIM To investigate whether the postoperative probiotics can modulate the inflammatory response and restore intestinal function in patients following appendectomy.METHODS This was a prospective,randomized trial.A total of 60 emergency patients were randomly divided into a control group(n=30)and a probiotic group(n=30).Patients in the control group started to drink some water the first day after surgery,and those in the probiotic group were given water supplemented with Bacillus licheniformis capsules for 5 consecutive days postsurgery.The indices of inflammation and postoperative conditions were recorded,and the data were analyzed with RStudio 4.3.2 software.RESULTS A total of 60 participants were included.Compared with those in the control group,the C-reactive protein(CRP),interleukin 6 and procalcitonin(PCT)levels were significantly lower in the probiotic group at 2 d after surgery(P=2.224e-05,P=0.037,and P=0.002,respectively,all P<0.05).This trend persisted at day 5 post-surgery,with CRP and PCT levels remaining significantly lower in the probiotic group(P=0.001 and P=0.043,both P<0.05).Furthermore,probiotics0.028,both P<0.05).CONCLUSION Postoperative oral administration of probiotics may modulate the gut microbiota,benefit the recovery of the early inflammatory response,and subsequently enhance recovery after appendectomy.

Ex vivo non-viral vector-mediated neurotrophin-3 gene transfer to olfactory ensheathing glia: effects on axonal regeneration and functional recovery after implantation in rats with spinal cord injury

Objective Combine olfactory ensheathing glia （OEG） implantation with ex vivo non-viral vector-based neurotrophin- 3 （NT-3） gene therapy in attempting to enhance regeneration after thoracic spinal cord injury （SCI）. Methods Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1 （＋）-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord （T9） contusion by the New York University impactor. The animals in 3 different groups received 4x 1050EG transfected with pcDNA3.1 （＋）-NT3 or pcDNA3.1 （＋） plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. Results NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1 （＋）-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Conclusion Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT- 3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats.

Effects of professional rehabilitation training on the recovery of neurological function in young stroke patients

Young stroke patients have a strong desire to return to the society, but few studies have been conducted on their rehabilitation training items, intensity, and prognosis. We analyzed clinical data of young and middle-aged/older stroke patients hospitalized in the Department of Neurological Rehabilitation, China Rehabilitation Research Center, Capital Medical University, China from February 2014 to May 2015. Results demonstrated that hemorrhagic stroke （59.6%） was the primary stroke type found in the young group, while ischemic stroke （60.0%） was the main type detected in the middle-aged/older group. Compared with older stroke patients, education level and incidence of hyperhomocysteinemia were higher in younger stroke patients, whereas, incidences of hypertension, diabetes, and heart disease were lower. The average length of hospital stay was longer in the young group than in the middle-aged/older group. The main risk factors observed in the young stroke patients were hypertension, drinking, smoking, hyperlipidemia, hyperhomocysteinemia, diabetes, previous history of stroke, and heart disease. The most accepted rehabilitation program consisted of physiotherapy, occupational therapy, speech therapy, acupuncture and moxibustion. Average rehabilitation training time was 2.5 hours/day. Barthel Index and modified Rankin Scale scores were increased at discharge. Six months after discharge, the degree of occupational and economic satisfaction declined, and there were no changes in family life satisfaction. The degrees of other life satisfaction （such as friendship） improved. The degree of disability and functional status improved significantly in young stroke patients after professional rehabilitation, but the number of patients who returned to society within 6 months after stroke was still small.

Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy

Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury（SCI）; however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the autophagy inhibitor 3-methyladenine（3-MA） in a rat model of SCI. The rats were randomly assigned to the SCI, lithium, 3-MA and sham groups. In the 3-MA group, rats were intraperitoneally injected with 3-MA（3 mg/kg） 2 hours before SCI. In the lithium and 3-MA groups, rats were intraperitoneally injected with lithium（LiCl; 30 mg/kg） 6 hours after SCI and thereafter once daily until sacrifice. At 2, 3 and 4 weeks after SCI, neurological function and diffusion tensor imaging indicators were remarkably improved in the lithium group compared with the SCI and 3-MA groups. The Basso, Beattie and Bresnahan locomotor rating scale score and fractional anisotropy values were increased, and the apparent diffusion coefficient value was decreased. Immunohistochemical staining showed that immunoreactivities for Beclin-1 and light-chain 3 B peaked 1 day after SCI in the lithium and SCI groups. Immunoreactivities for Beclin-1 and light-chain 3 B were weaker in the 3-MA group than in the SCI group, indicating that 3-MA inhibits lithium-induced autophagy. Furthermore, NeuN＋ neurons were more numerous in the lithium group than in the SCI and 3-MA groups, with the fewest in the latter. Our findings show that lithium reduces neuronal damage after acute SCI and promotes neurological recovery by inducing autophagy. The neuroprotective mechanism of action may not be entirely dependent on the enhancement of autophagy, and furthermore, 3-MA might not completely inhibit all autophagy pathways.

Electroacupuncture promotes the recovery of motor neuron function in the anterior horn of the injured spinal cord

Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury was established by compressing the T8-9 segments using a modified Nystrom method.Twenty-four hours after injury,Zusanli（ST36）,Xuanzhong（GB39）,Futu（ST32）and Sanyinjiao（SP6）were stimulated with electroacupuncture.Rats with spinal cord injury alone were used as controls.At 2,4 and 6 weeks after injury,acetylcholinesterase（ACh E）activity at the site of injury,the number of medium and large neurons in the spinal cord anterior horn,glial cell line-derived neurotrophic factor（GDNF）m RNA expression,and Basso,Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group.These results demonstrate that electroacupuncture increases ACh E activity,up-regulates GDNF m RNA expression,and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury.

Combination of methylprednisolone and rosiglitazone promotes recovery of neurological function after spinal cord injury

Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-y in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally rejected with methylprednisolone （30 mg/kg） and rosiglitazone （2 mg/kg） at 1 hour after injury, and methylprednisolone （15 mg/kg） at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better pro- moted recovery of neurological function after injury.

Transdermal delivery of 4-aminopyridine accelerates motor functional recovery and improves nerve morphology following sciatic nerve crush injury in mice

Oral 4-aminopyridine(4-AP)is clinically used for symptomatic relief in multiple sclerosis and we recently demonstrated that systemic 4-AP had previously unknown clinically-relevant effects after traumatic peripheral nerve injury including the promotion of re-myelination,improvement of nerve conductivity,and acceleration of functional recovery.We hypothesized that,instead of oral or injection administration,transdermal 4-AP(TD-4-AP)could also improve functional recovery after traumatic peripheral nerve injury.Mice with surgical traumatic peripheral nerve injury received TD-4AP or vehicle alone and were examined for skin permeability,pharmacokinetics,functional,electrophysiological,and nerve morphological properties.4-AP showed linear pharmacokinetics and the maximum plasma 4-AP concentrations were proportional to TD-4-AP dose.While a single dose of TD-4-AP administration demonstrated rapid transient improvement in motor function,chronic TD-4-AP treatment significantly improved motor function and nerve conduction and these effects were associated with fewer degenerating axons and thicker myelin sheaths than those from vehicle controls.These findings provide direct evidence for the potential transdermal applicability of 4-AP and demonstrate that 4-AP delivered through the skin can enhance in-vivo functional recovery and nerve conduction while decreasing axonal degeneration.The animal experiments were approved by the University Committee on Animal Research(UCAR)at the University of Rochester(UCAR-2009-019)on March 31,2017.