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Cerebral organoids are three-dimensional nerve cultures induced by embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)that mimic the structure and function of human brain.With the continuous optimization of cerebral organoid culture technology and the combination with emerging technologies such as organ transplantation,gene editing and organoids-on-chip,complex brain tissue structures such as functional vascular structures and neural circuits have been produced,which provides new methods and ideas for studying human brain development and diseases.This article reviews the latest advances in brain organoid technology,describes its application in neurological diseases and advances in stroke modeling and transplantation treatment.
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Post-stroke cognitive impairment(PSCI)is mainly manifested as learning and memory disorders.Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation.Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI,it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI.This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation,which will provide reference for researchers in this field.
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BACKGROUND:Long non-coding RNAs(lncRNAs),as important regulators of the inflammatory response,are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE:To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways,pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS:PubMed was searched using the search terms of"ischemic stroke,long non-coding RNA,neuroinflammation,immune function,signal pathway,microglia,astrocytes,oligodendrocyte,mechanism,"and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION:In the early stage of ischemic stroke,the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain,promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses.As an important pathogenesis factor in ischemic stroke,the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke,and it needs to be suppressed promptly in the early stage.Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia,astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects.LncRNAs,as important regulatory factors of the inflammatory response,inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB,lncRNA-miRNA-mRNA axis,Rho-ROCK,MAPK,AKT,ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke.Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model,but no clinical trials have been conducted.Therefore,it remains to be further explored about whether lncRNAs can be safely applied in clinical practice.At present,there are many therapeutic drugs for the treatment of ischemic stroke,but there are relatively few studies on the application of lncRNAs,exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology,which need to be further explored.lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity.In future studies,more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored,in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke.
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BACKGROUND:Our previous studies found that adding barium sulfate could improve the mechanical and radiopaque properties of calcium phosphate cement.However,with the degradation of calcium phosphate,the remaining radiopaque agent is difficult to degrade,and the space-occupying and osteoclast effects at the implantation site affect the bone repair process.Therefore,it is necessary to develop a new biodegradable radiopaque material. OBJECTIVE:To discuss the radiopaque ability of bioactive degradable material strontium polyphosphate(SrPP)and its impact on the physicochemical properties and osteogenic effect of calcium phosphate cement. METHODS:(1)Calcium phosphate cement(CPC),starch modified calcium phosphate cement(CPS)and starch modified calcium phosphate cement(20%SrPP-CPN)containing SrPP(20%mass fraction of bone cement powder)were prepared respectively,and the physicochemical properties of the three groups of bone cements were characterized.(2)The three groups of bone cement extracts were co-cultured with rat bone marrow mesenchymal stem cells,respectively,to detect cell proliferation,energy metabolism,and osteogenic differentiation.(3)Bone defects with a diameter of 5 mm were made on each side of the top of the skull of 24 SD rats,and they were randomly divided into control group(without any intervention),CPC group,CPS group,and 20%SrPP-CPN group for intervention,with 6 rats in each group.Relevant tests were performed after 4 and 12 weeks of intervention. RESULTS AND CONCLUSION:(1)Compared with the other two groups of bone cement,20%SrPP-CPN had enhanced radiopaque ability,increased compressive strength and degradation rate,and prolonged curing time,and 20%SrPP-CPN could release Sr2+ stably during degradation.(2)CCK-8 assay showed that 20%SrPP-CPN did not affect the proliferation of bone marrow mesenchymal stem cells.Cell starvation test(serum-free culture)showed that 20%SrPP-CPN could promote the proliferation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.Compared with the other two groups of bone cements,20%SrPP-CPN increased adenosine triphosphate concentration in bone marrow mesenchymal stem cells.Alkaline phosphatase and alizarin red staining showed that 20%SrPP-CPN could promote osteogenic differentiation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.(3)In the rat skull defect experiment,Micro-CT scanning and histological observation(hematoxylin-eosin and Masson stainings)showed that bone cement in 20%SrPP-CPN group was significantly degraded compared with that in CPC and CPS groups,and a large number of new bone tissues were dispersed in degraded bone cement.Immunohistochemical staining showed that Runx2 protein expression was increased in 20%SrPP-CPN group compared with CPC group and CPS group(P＜0.01).(4)These results show that 20%SrPP-CPN has good radiopaque ability and osteogenic properties.
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As a key regulator of neuronal growth， development and synaptic plasticity， BDNF/ TrkB signaling pathway is widely involved in the occurrence and development of central nervous system diseases， such as ischemic stroke， Alzheimer's disease， Parkinson's disease and spinal cord injury. Studies have shown that acupuncture can regulate the activity of BDNF/TrkB signaling pathway， and has significant therapeutic potential for these diseases. Its mechanism of action is related to participating in synaptic remodeling， inhibiting neuronal apoptosis， and promoting neurogenesis or synaptic regeneration. This article reviews the role of BDNF/TrkB signaling pathway in central nervous system diseases and the regulation mechanism of acupuncture on this pathway， in order to provide new ideas for clinical treatment. Future studies should further explore the precise regulatory mechanism of acupuncture on BDNF/TrkB signaling pathway in order to develop more efficient and safe treatment strategies.
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Bone cement-augmented pedicle screw system demonstrates great efficacy in spinal disease treatments. However, the intrinsic drawbacks associated with clinically used polymethylmethacrylate (PMMA) cement demands for new bone cement formulations. On the basis of our previous studies, a novel injectable and biodegradable calcium phosphate-based nanocomposite (CPN) for the augmentation of pedicle screw fixation was systematically evaluated for its surgical feasibility and biomechanical performance by simulated and animal osteoporotic bone models, and the results were compared with those of clinical PMMA cement. ASTM-standard solid foam and open-cell foam models and decalcified sheep vertebra models were employed to evaluate the augmentation effects of CPN on bone tissue and on the cement-injected cannulated pedicle screws (CICPs) placed in osteoporotic bone. Surgical factors in CICPs application, such as injection force, tapping technique, screw diameter, and pedicle screw loosening scenarios, were studied in comparison with those in PMMA. When directly injected to the solid foam model, CPN revealed an identical augmentation effect to that of PMMA, as shown by the similar compressive strengths (0.73 ± 0.04 MPa for CPN group vs. 0.79 ± 0.02 MPa for PMMA group). The average injection force of CPN at approximately 40-50 N was higher than that of PMMA at approximately 20 N. Although both values are acceptable to surgeons, CPN revealed a more consistent injection force pattern than did PMMA. The dispersing and anti-pullout ability of CPN were not affected by the surgical factors of tapping technique and screw diameter. The axial pullout strength of CPN evaluated by the decalcified sheep vertebra model revealed a similar augmentation level as that of PMMA (1351.6 ± 324.2 N for CPN vs. 1459.7 ± 304.4 N for PMMA). The promising results of CPN clearly suggest its potential for replacing PMMA in CICPs augmentation application and the benefits of further study and development for clinical uses.
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Objective To investigate the efficacy of acupuncture combined with doctor-nurse cooperation mode on stroke-associated pneumonia in patients with acute stroke. Methods 67 patients of acute stroke within 1 week in our hospital from March, 2013 to January, 2015 were randomly divided into control group (n=35) and treatment group (n=32). Both groups received neurological routine treatment and systematic rehabilitation training by professional physiotherapists under general nursing mode. The treatment group received acupuncture treatment under doctor-nurse cooperation mode additionally. Incidence of stroke-associated pneumonia, swallow function and aspiration rate were recorded. Results Compared with the control group, the incidence of stroke-associated pneumonia significantly decreased in the treat-ment group after treatment (χ2=4.615, P=0.032). The retention volume of epiglottic vallecula and pyriform sinus (tdilute barium=21.01, tthick barium=19.85), the duration of pharynx period (tdilute barium=17.03, tthick barium=13.68), and the start time of pharynx period (tdilute barium=19.63, tthick barium=17.86) were less in the treatment group than in the control group (P0.05). Conclusion Acupuncture combined doctor-nurse cooperation mode may decrease the rates of aspiration and stroke-associated pneumonia in acute stroke patients through improving their swallow function.
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Objective To compare the effects of platelet rich fibrin(PRF)and concentrated growth factors(CGF)using Schwann cells as a pe?ripheral nerve model. Methods A total of 10 healthy volunteers aged 18 to 55 were randomly selected,and 10 mL venous blood was collected un?der aseptic conditions to prepare PRF and CGF. The cells were randomly divided into three groups,control group,PRF group and CGF group. The cell morphology was observed by inverted phase contrast microscope. The cell proliferation was analyzed by MTT assay. The secretion of nerve growth factor in supernatant was detected by enzyme?linked immunosorbent assay. Cell cycle was detected by flow cytometry. Results There was no significant difference of the morphology of cells in each group as observed under inverted phase contrast microscope. MTT results showed that the absorbance values of PRF group and CGF group were significantly higher than those of the control group(P<0.05). The secretion of nerve growth factor in the supernatant were significantly increased(P<0.05). The number of cells in S+G2M phase was significantly increased(P<0.01),but there was no significant difference between PRF group and CGF group. Conclusion Both PRF and CGF can promote proliferation of Schwann cells and increased the amount of nerve growth factor secretion ,but there is no significant difference between PRF and CGF in terms of improving cell proliferation and promoting nerve growth factor secretion.