Search

Objective. Methane saline (MS) can be used to treat many diseases via its anti-inflammatory, antiapoptotic, and antioxidative activities. However, to date, there is no published evidence as to whether MS has any effect on traumatic brain injury (TBI). The Wnt signalling pathway regulates cell proliferation, differentiation, migration, and apoptosis; however, whether the Wnt signalling pathway regulates any effect of MS on TBI is unknown. This study was designed to explore the role of MS in the treatment of TBI and whether the Wnt pathway is involved. Methods. Sprague-Dawley rats were randomly divided into five groups: sham, TBI, TBI+10 ml/kg MS, TBI+20 ml/kg MS, and TBI+30 ml/kg MS. After induction of TBI, MS was injected intraperitoneally once daily for seven consecutive days. Neurological function was evaluated by the Neurological Severity Score (NSS) at 1, 7, and 14 days after TBI. Haematoxylin-eosin (HE) staining, inflammatory factors, neuron-specific enolase (NSE) staining, oxidative stress, and cell apoptosis were measured and compared 14 d after TBI to identify the optimal dose of MS and to investigate the effect of MS on TBI. In the second experiment, Sprague-Dawley rats were randomly divided into four groups: sham, TBI, TBI+20 ml/kg MS, and TBI+20 ml/kg MS+Dickkopf-1 (DKK-1, a specific inhibitor of the Wnt pathway). NSE, caspase-3, superoxide dismutase (SOD), Wnt3a, and β-catenin were detected by real-time PCR and Western blotting. The results from each group were compared 14 d after TBI to determine the regulatory role of the Wnt pathway. Results. Methane saline significantly inhibited inflammation, oxidative stress, and cell apoptosis, thus protecting neurons within 14 days of TBI. The best treatment effect against TBI was obtained with 20 ml/kg MS. When the Wnt pathway was inhibited, the treatment effect of MS was impaired. Conclusion. Methane saline ameliorates TBI through its anti-inflammatory, antiapoptotic, and antioxidative effects via activation of the Wnt signalling pathway, which plays a part but is not the only mechanism underlying the effects of MS. Thus, MS may be a novel strategy for treating TBI.

Background Open reduction and internal fixation (ORIF) is the preferred choice for treating clavicle fractures. The brachial plexus injury caused by ORIF of a clavicle fracture is very rare. If it is not treated in time, the function of the brachial plexus will be challenging to recover, which will eventually lead to upper limb dysfunction and seriously affect the patient’s quality of life. Our team recently used ORIF to treat a patient with a clavicle fracture, who developed brachial plexus injury symptoms after surgery. Case presentation A 34-year-old female patient was admitted to the hospital for 13 h due to the right shoulder movement restriction after a fall. Due to the significant displacement of the fracture, we used ORIF to treat the fracture. The surgery went well. When the anaesthesia effect subsided 12 h after the operation, the patient developed right brachial plexus injury symptoms, decreased right upper limb muscle strength, dysfunction, and hypoesthesia. Symptomatic treatments, such as nourishing nerve and electrical stimulation, were given immediately. Sixty days after the operation, the patient’s brachial plexus injury symptoms disappeared, and the function of the right upper limb returned to the preoperative state. Conclusions Patients with clavicle fractures usually need to undergo a careful physical examination before surgery to determine whether symptoms of brachial plexus injury have occurred. Anaesthesia puncture requires ultrasound guidance to avoid direct damage to the brachial plexus. When the fracture end is sharp, reset should be careful to prevent nerve stump stabbed. When using an electric drill to drill holes, a depth limiter should be installed in advance to prevent the drill from damaging the subclavian nerve and blood vessels. When measuring the screw depth, the measuring instrument should be close to the bone surface and sink slowly to avoid intense hooks and damage to the brachial plexus. Try to avoid unipolar electrosurgical units to prevent heat conduction from damaging nerves, and bipolar electrocoagulation should be used instead. If symptoms of brachial plexus injury occur after surgery, initial symptomatic treatment is drugs and functional exercise, and if necessary, perform surgical exploration.

Objectives: Spinal cord injury (SCI) is a most debilitating traumatic injury, and cytotherapy is a promising alternative treatment strategy. Here we investigated the effect and mechanism of adipose-derived stem/stromal cells (ASCs) with overexpressing brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) (BDNF-NT3) in combination with silk fibroin/chitosan scaffold (SFCS) in SCI.Methods: Female Sprague-Dawley rats were used as an SCI model. SFCS,SFCS and ASCs, or ASCs overexpressing NT3, BDNF, and BDNF-NT3 were implanted into SCI rats. Basso, Beattie, and Bresnahan score, pathological changes, and spinal cord tissue and nerve fiber morphology were observed and assayed. GAP-43, GFAP, and caspase-3 expression was determined using immunohistochemistry and western blotting.Results: Smoother spinal cords, less scar tissue, and lower inflammatory activity were found in the SFCS, SFCS and ASCs, ASCs with NT3, BDNF, and BDNF-NT3 overexpression treatment than in the untreated SCI rat groups. Increasing formation of nerve fibers was observed in the above groups in order. GAP-43 expression significantly increased, while GFAP and caspase-3 expression significantly decreased. These results indicated obvious alleviation in pathological changes and BDNF-NT3 overexpression in ASCs combined with SFCS treatment in SCI rats.Conclusion: Thus, BDNF-NT3 overexpression from ASCs with SFCS had synergistic neuroprotective effects on SCI and may be a treatment option for SCI.

Introduction Spinal cord impact is a mature method for building models of spinal cord injury (SCI). However, a common problem is that the degree of elicited paralysis may not be identical even though animals receive the same impact. We hypothesize that this difference may be caused by the difference in the secondary injury mechanism of SCI and there might be an impact dosage named “median paralyzing dose (PD50)”, similar as the “median lethal dose (LD50)” in pharmacology. In addition, since SCI is a result of multiple mechanisms, we hypothesize that it is more suitable to employ multiple regression analysis to analyze the related factors for complete paraplegia. So the present study aimed to calculate the existence of PD50 and analyze the related factors of SCI-induced complete paralysis using logistic regression under the PD50 which represents identical primary injury. Material and methods Rat models of SCI were built using the weight-drop method under PD50. PD50 was calculated by Karber’s method. Rats were allocated into two groups according to whether they developed complete or incomplete paralysis 2 weeks after injury. Cavity and spared tissues in the two groups were compared. Neuronal preservation, microglia/macrophage reaction, T-lymphocyte infiltration, astrocyte activation and neuronal apoptotic were compared by immunohistochemistry. The logistic regression model was constructed and significant related factors of complete paralysis were selected. Results Of the two groups, the cavity in the injured spinal cord of the complete-paralysis rats was significantly larger and the spared white matter volume (SWMV%) was obviously smaller. Whereas, the spared grey matter volume was not different between groups. Macrophage reaction, T-lymphocyte infiltration and neuronal apoptosis were significantly more severe in the complete-paralysis rats. Astrocyte activation and neuronal preservation showed no difference between groups. Logistic regression analysis showed that cavity volume, SWMV%, microglia/macrophage reaction and neuronal apoptosis were significantly correlated with SCI-induced complete paralysis. Conclusion As a non-mainstream method, it is feasible to analyze the secondary factors of SCI-induced complete paralysis using multiple regression analysis in the condition of identical primary injury (PD50). SWMV% and microglia/macrophage reaction are important factors that contribute to complete paralysis at the early phase of severe SCI.

The therapeutic effect of stem cell transplantation in traumatic spinal cord injury (SCI) has been extensively studied these days, and evidence has shown that stem cell-derived exosomes and exosome-shuttled miRNA (e.g. miR-21) contribute to the protective effects of stem cell transplantation against SCI. It has been reported that obesity, a prevalent metabolic disorder, reshapes stem cells and their extracellular vesicles. However, the effects of exosomes derived from obese rat stem cells on SCI and its underlying mechanism remain unknown. Here, we examined the effects of exosomes derived from obese rat mesenchymal stem cells (MSCs) on SCI, and tested the role of miR-21 in their effects. We found that exosomes derived from obese rat MSCs showed decreased miR-21 levels and did not exert protective effects against SCI. Overexpression of miR-21 in obese rat MSCs restored the protective effects of exosomes purified from obese rat MSCs against SCI. In addition, obese rat MSCs showed insulin resistance, and MSC insulin resistance decreased miR-21 levels in its secreted exosomes. These results suggested that miR-21 deficiency in obese rat MSCs contributes to the impaired protective effects of obese rat MSCs-derived exosomes against SCI, and further reinforced the notion that miR-21 is a potential molecule for treatment of SCI.

The increased prevalence of obesity is recognized as a serious public health problem affecting millions of people. Although some anti-obesity drugs are currently licensed for use, these drugs involve diverse side effects such as diarrhea, vomiting, and low efficiency. Here we developed a safe and efficient biomaterials-based anti-obesity nanosystem (PCG-EPL/miR33agonist), which was formed with poly (citric acid)-glycerol-polylysine (PCG-EPL) and miR33 agonist by self-assembly. The PCG-EPL could efficiently load, protect and deliver the miR33 agonist into the adipocytes and decreased the obesity-related IL-1β expression in adipocytes in vitro. The high-fat diet induced obese rat model experiment showed that the PCG-EPL/miR33agonist via caudal vein injection effectively reduced the body weight by enhancing lipid metabolism and decreasing the inflammatory factors expressions (IL-1β, TNF-α and IL-6) in vivo, without suppressing the appetite of rat. Compared with the obese mice, mice in PCG-EPL/miR33 had higher average food intake but lower energy conversion rate. PCG-EPL/miR33agonist significantly inhibited the growth of adipocytes. Noteworthy, this weight loss strategy is not only safe and efficient, but also does not need diet control. Thus, PCG-EPL may serve as an ideal platform for RNA drug delivery in anti-obesity therapy, especially for those who need to lose weight but unable to autonomously control their diet.

Rolipram, a phosphodiesterase-4 inhibitor, can activate the cyclic adenosine monophosphate (cAMP)/cAMP-responsive element binding protein (CREB) pathway to facilitate functional recovery following ischemic stroke. However, to date, the effects of rolipram on angiogenesis and cerebral ischemia-induced neuronal apoptosis are yet to be fully elucidated. In this study, the aim was to reveal the effect of rolipram on the angiogenesis and neuronal apoptosis following brain cerebral ischemia. Rat models of ischemic stroke were established following transient middle cerebral artery occlusion and rolipram was administered for three, seven and 14 days. The results were examined using behavioral tests, triphenyl tetrazolium chloride staining, immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to evaluate the effects of rolipram therapy on functional outcome, angiogenesis and apoptosis. Western blot analysis was used to show the phosphorylated- (p-)CREB protein level in the ischemic hemisphere. The rolipram treatment group exhibited a marked reduction in infarct size and modified neurological severity score compared with the vehicle group, and rolipram treatment significantly promoted the microvessel density in the ischemic boundary region and increased p-CREB protein levels in the ischemic hemisphere. Furthermore, a significant reduction in the number of TUNEL-positive cells was observed in the rolipram group compared with the vehicle group. These findings suggest that rolipram has the ability to attenuate cerebral ischemic injury, stimulate angiogenesis and reduce neuronal apoptosis though the cAMP/CREB pathway.

Spinal cord injury (SCI) may lead to a devastating and permanent loss of neurological function, which may place a great economic burden on the family of the patient and society. Methods for reducing the death of neuronal cells, inhibiting immune and inflammatory reactions, and promoting the growth of axons in order to build up synapses with the target cells are the focus of current research. Target cells are located in the damaged spinal cord which create a connect with the scaffold. As tissue engineering technology is developed for use in a variety of different areas, particularly the biomedical field, a clear understanding of the mechanisms of tissue engineering is important. This review establishes how this technology may be used in basic experiments with regard to SCI and considers its potential future clinical use.

Introduction Adipose-derived stem cells (ADSCs) possess the potential of multi-differentiation which could differentiate into neuronal cells and Schwann cells under certain conditions. If we inoculate the ADSCs modified by Brain derived neurophic factor(BDNF) and Neurotrophin-3(NT-3)double genes on the silk fibroin/chitosan (SFCS), and transplant it into 2 mm pre-made spinal cord transection animal model, we can take advantage of the characteristic of ADSCs which could express BDNF and NT-3 stably after being double gene modified and the advantage of tissue engineering, we look forward to providing a new treatment method for spinal cord injury (SCI), which thereby could reduce SCI morbidity and mortality rate, so as to build up a solid theoretical foundation for the clinical treatment of SCI. Material and Methods According to the preliminary design, animal experiment is divided into seven groups: Group A: SFCS/ADSCs/Lenti-BDNF-GFP-NT-3-RFP, namely, BDNF and NT-3 double genes co-transfect ADSCs combining SFCS group; Group B: SFCS/ADSCs/Lenti-BDNF-GFP, namely, BDNF single gene transfect ADSCs combining SFCS group; Group C: SFCS/ADSCs/ Lenti-NT-3-RFP, namely, NT-3 single gene transfect ADSCs combining SFCS group; Group D: SFCS/ADSCs/Lenti-eGFP, namely, empty vector transfect ADSCs combining SFCS group; Group E:SFCS, namely, single SFCS group; Group F:only cut off spinal cord and without treatment; Group G: normal control group, just open the vertebral plate without any treatment. Group A, B, C, D and E transplant the scaffold into 2 mm spinal cord transection defect rat model. Group F cuts off spinal cord and makes 2 mm defect, Group G is normal group. Do a BBB scoring at 1 w, 4 w, 8 w and 12 w after surgery to analyze functional recovery, execute the rats 12 w later, take out the scaffolds, test them by HE staining, immunehistochemical staining (NSE, GAP-43, Caspase-3, GFAP), LFB staining, RT-PCR and Western blot, the purpose of which is to observe the effect of tissue engineering on the recovery of SCI. Results Group A (BDNF and NT-3 double genes modified ADSCs combining the use of SFCS group) has a better repair effect on rats spinal cord transection injury treatment, which reveals higher BBB scores, increased GAP-43 expression, more positive NSE cells, decreased expression of GFAP and Caspase-3. At the same time denser regenerating nerve fiber could move through the scaffold, and the most important thing is the repair effect of Group A is better than single gene modified Group B and Group C, which is better than Group D (empty vector transfect ADSCs combining SFCS group), which is better than Group E (single use SFCS), which is better than Group F (just cut off spinal cord and without treatment). Conclusion Under the guidance of tissue engineering method, ADSCs modified by BDNF and NT-3 double genes combining the use of SFCS can significantly reduce the inflammatory response after injury, inhibit scar hyperplasia and cell apoptosis and promote nerve fibers regeneration and the differentiation of ADSCs into neurons in vivo, so as to improve the repair effect of rat spinal cord transection injuries, which provides a new method for the treatment of SCI.

Spinal cord injury usually leads to permanent disability, which could cause a huge financial problem to the patient. Up to now there is no effective method to treat this disease. The key of the treatment is to enable the damage zone axonal regeneration and luckily it could go through the damage zone; last a connection can be established with the target neurons. This study attempts to combine stem cell, material science and genetic modification technology together, by preparing two genes modified adipose-derived stem cells and inducing them into neuron direction; then by compositing them on the silk fibroin/chitosan scaffold and implanting them into the spinal cord injury model, seed cells can have features of neuron cells. At the same time, it could stably express the brain-derived neurotrophic factor and neurotrophin-3, both of which could produce synergistic effects, which have a positive effect on the recovery of spinal cord. The spinal cord scaffold bridges the broken end of the spinal cord and isolates with the surrounding environment, which could avoid a scar effect on the nerve regeneration and provide three-dimensional space for the seed cell growth, and at last we hope to provide a new treatment for spinal cord injury with the tissue engineering technique.