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Intracerebral hemorrhage (ICH) is a common subtype of stroke and places a great burden on the family and society with a high mortality and disability rate and a poor prognosis. Many findings from imaging and pathologic studies have suggested that cerebral ischemic lesions visualized on diffusion-weighted imaging (DWI) in patients with ICH are not rare and are generally considered to be associated with poor outcome, increased risk of recurrent (ischemic and hemorrhagic) stroke, cognitive impairment, and death. In this review, we describe the changes in cerebral blood flow (CBF) and DWI lesions after ICH and discuss the risk factors and possible mechanisms related to the occurrence of DWI lesions, such as cerebral microangiopathy, cerebral atherosclerosis, aggressive early blood pressure lowering, hyperglycemia, and inflammatory response. We also point out that a better understanding of cerebral DWI lesions will be a key step toward potential therapeutic interventions to improve long-term recovery for patients with ICH.

Astrocytes are promising source cells to replace neurons lost to disease owing to a shared lineage and capacities for dedifferentiation and proliferation under pathological conditions. Reprogramming of astrocytes to neurons has been achieved by transcription factor modulation, but reprogramming in vitro or in vivo using small‐molecule drugs may have several advantages for clinical application. For instance, small molecules can be extensively characterized for efficacy, toxicity, and tumorigenicity in vitro; induce rapid initiation and subsequent reversal of transdifferentiation upon withdrawal, and obviate the need for exogenous gene transfection. Here we report a new astrocyte–neuron reprogramming strategy using a combination of small molecules (0.5 mM valproic acid, 1 μM RepSox, 3 μM CHIR99021, 2 μM I‐BET151, 10 μM ISX‐9, and 10 μM forskolin). Treatment with this drug combination gradually reduced expression levels of astroglial marker proteins (glial fibrillary acidic protein and S100), transiently enhanced expression of the neuronal progenitor marker doublecortin, and subsequently elevated expression of the mature neuronal marker NeuN in primary astrocyte cultures. These changes were accompanied by transition to a neuron‐like morphological phenotype and expression of multiple neuronal transcription factors. Further, this drug combination induced astrocyte‐to‐neuron transdifferentiation in a culture model of intracerebral hemorrhage (ICH) and upregulated many transdifferentiation‐associated signaling molecules in ICH model rats. In culture, the drug combination also reduced ICH model‐associated oxidative stress, apoptosis, and pro‐inflammatory cytokine production. Neurons derived from small‐molecule reprogramming of astrocytes in adult Sprague–Dawley rats demonstrated long‐term survival and maintenance of neuronal phenotype. This small‐molecule‐induced astrocyte‐to‐neuron transdifferentiation method may be a promising strategy for neuronal replacement therapy.

The 17th National Annual Conference on Neurological Infectious Diseases and Cerebrospinal Fluid Cytology of the Chinese Medical Association Neurology Branch was successfully held in Wuhan, Hubei, China. During the conference, many well-known neurology experts in China conducted in-depth and detailed discussions on the research progress of infectious diseases of the nervous system and cerebrospinal fluid cytology, which benefited the participants a lot.

Acute Ischemic Stroke (AIS) is currently the most frequently reported neurological complication of Coronavirus disease 2019 (COVID-19). This article will elaborate the clinical features of inpatients with COVID-19 and AIS and the pathophysiological mechanism of AIS under the background of COVID-19. Through a detailed search of relevant studies, we found that the incidence of AIS among COVID-19 patients varied from 0.9% to 4.6%, and AIS has been observed in many people without an underlying disease and cardiovascular risk factors as well as young people. The National Institute of Health Stroke Scale (NIHSS) score of COVID-19 patients with AIS was higher than historical AIS patients, and the proportion of large vessel occlusion (LVO) was about 64.2%. COVID-19 patients with AIS generally have high levels of D-D dimer, fibrinogen, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), suggesting systemic hyperinflammatory and hypercoagulable state. The pooled mortality of COVID-19 patients with AIS was 38% and the mortality of LVO patients is higher (45.9%). Compared with COVID-19-negative AIS patients in the same period in 2020 and 2019, COVID-19 patients with AIS had a worse prognosis.

Hyperhomocysteinemia (HHcy) is independently associated with poorer long-term prognosis in patients with intracerebral haemorrhage (ICH); however, the effect and mechanisms of HHcy on ICH are still unclear. Here, we evaluated neurite outgrowth and neurological functional recovery using simulated models of ICH with HHcy in vitro and in vivo. We found that the neurite outgrowth velocity and motor functional recovery in the ICH plus HHcy group were significantly slower than that in the control group, indicating that homocysteine (Hcy) significantly impedes the neurite outgrowth recovery after ICH. Furthermore, phosphoproteomic data and signalome analysis of perihematomal brain tissues suggested that calmodulin-dependent protein kinases 2 (CAMK2A) kinase substrate pairs were significantly downregulated in ICH with HHcy compared with autologous blood injection only, both western blot and immunofluorescence staining confirmed this finding. Additionally, upregulation of pCAMK2A significantly increased neurite outgrowth recovery in ICH with HHcy. Collectively, we clarify the mechanism of HHcy-hindered neurite outgrowth recovery, and pCAMK2A may serve as a therapeutic strategy for promoting neurological recovery after ICH.

Minimally invasive surgery has been widely used in the treatment of patients with intracerebral hemorrhage in recent years, and has achieved good clinical efficacy. Based on the basic theory of minimally invasive surgery, indications and contraindications are discussed, and then the minimally invasive preoperative preparation, intraoperative operation, postoperative management, and other aspects are systematically discussed. Finally, the application of microsurgery in the precise treatment of intracerebral hemorrhage is further prospected.

Pronounced inflammation after intracerebral hemorrhage (ICH) contributes to secondary brain injury, which seriously affects the prognosis of ICH patients. Fractalkine (FKN)/CX3CR1 pathway may play an important role in regulating inflammatory reactions after ICH. As resident immunocyte in brain, microglia is essential for inflammatory reactions in central nervous system. This study intends to explore the effect of FKN/CX3CR1 pathway on microglia after experimental ICH and its possible mechanisms. In mouse ICH models, FKN and TGF-β1 levels gradually increased and showed a positive correlation, both of which peaked at the third day after ICH model. Compared with ICH only, the ratio of s-FKN/m-FKN, microglia activation, and neuronal apoptosis were all decreased after injecting ADAM10 inhibitor (G1254023X) into the lateral ventricle. The expression of inflammatory factors were increased after stimulation with hemin in BV2 cells. The addition of m-FKN reduced the inflammatory response to a certain extent, and the inhibitor of TGF-β1 could counteract the effect of m-FKN. In conclusion, in mouse ICH model, the expression of FKN is increased, and m-FKN may inhibit the activation of microglia and reduce neuron apoptosis by promoting the expression of TGF-β1.

Objective The main aims of the study were to explore the correlation between different times of a minimally invasive operation and perihaematomal oedema properties in patients with cerebral hemorrhage, to identify the optimal time window for a minimally invasive operation and to observe the effect of different doses of urokinase on perihaematomal oedema properties. Methods A retrospective analysis was performed on 95 patients with cerebral hemorrhage who were treated in the Department of Neurology at the Tianmen First People’s Hospital between April 2014 and December 2017. Finally, 66 valid cases were included, and they were divided into three groups according to the time from onset to the minimally invasive operation. Haematoma volume and oedema volume before the surgery, 4 days after the surgery and 14 days after the surgery were compared among the three groups. Results There was no significant difference in postoperative oedema volume among the three groups. The difference in haematoma volume among the three groups may be related to haematoma absorption after a long period of time. There was no significant linear correlation between the timing of surgery and the dosage of urokinase or the perihaematomal oedema volume in the three groups. There was no significant difference in the rebleeding rate and pulmonary infection complication rate among the three groups. Conclusions The operation timing of minimally invasive puncture haematoma removal in patients with cerebral hemorrhage has no obvious influence on perihaematomal oedema, rebleeding and pulmonary infection complications. This study has limitations, and a prospective cohort study with a larger sample size is needed to explore the details, such as patient selection and the timing of minimally invasive surgery.

Stroke is the second leading cause of death worldwide. Therefore, research on prevention and treatment for stroke has great significance. In recent years, the development of artificial intelligence (AI) technology has brought new hopes to healthcare. The resulting partnerships between clinicians and computation science scientists, supported by growing strength of clinical informatics, are beginning to yield positive results. AI techniques have been used successfully in skin/cancer-related studies. Besides that, AI also have been used more and more in the field of stroke. In this review we summarized the application of artificial intelligence in the four main areas of stroke care: diagnosis, outcome prediction, treatment and rehabilitation. Finally, we look forward to the current studies of AI-assisted medical care and make some suggestions for the future potential development direction.

ObjectivesTo systematically review the efficacy and safety of anti-inflammatory agents for patients with major depressive disorders.MethodsWe searched the literature to identify potentially relevant randomised controlled trials (RCTs) up to 1 January 2019. The primary outcome was efficacy, measured by mean changes in depression score from baseline to endpoint. Secondary outcomes included response and remission rates and quality of life (QoL). Safety was evaluated by incidence of classified adverse events. Heterogeneity was examined using the I2 and Q statistic. Pooled standard mean differences (SMDs) and risk ratios (RRs) were calculated. Subgroup meta-analyses were conducted based on type of treatment, type of anti-inflammatory agents, sex, sponsor type and quality of studies.ResultsThirty RCTs with 1610 participants were included in the quantitative analysis. The overall analysis pooling from 26 of the RCTs suggested that anti-inflammatory agents reduced depressive symptoms (SMD −0.55, 95% CI −0.75 to −0.35, I2=71%) compared with placebo. Higher response (RR 1.52, 95% CI 1.30 to 1.79, I2=29%) and remission rates (RR 1.79, 95% CI 1.29 to 2.49, I2=41%) were seen in the group receiving anti-inflammatory agents than in those receiving placebo. Subgroup analysis showed a greater reduction in symptom severity in both the monotherapy and adjunctive treatment groups. Subgroup analysis of non-steroidal anti-inflammatory drugs, omega-3 fatty acids, statins and minocyclines, respectively, disclosed significant antidepressant effects for major depressive disorder (MDD). For women-only trials, no difference in changes of depression severity was found between groups. Subanalysis stratified by sponsor type and study quality led to the same outcomes in favour of anti-inflammatory agents in both subgroups. Changes of QoL showed no difference between the groups. Gastrointestinal events were the only significant differences between groups in the treatment periods.ConclusionsResults of this systematic review suggest that anti-inflammatory agents play an antidepressant role in patients with MDD and are reasonably safe.

Primary brainstem hemorrhage (PBSH) is the most fatal subtype of intracerebral hemorrhage and is invariably associated with poor prognosis. Several prognostic factors are involved, of which the two most predominant and consistent are the initial level of consciousness and hemorrhage size. Other predictors, such as age, hyperthermia, and hydrocephalus, are generally not dependable indicators for making prognoses. Scoring systems have now been developed that can predict mortality and functional outcomes in patients suffering from PBSH, which can thus guide treatment decision-making. A novel grading scale, entitled “the new primary pontine hemorrhage (PPH) score,” represents the latest approach in scoring systems. In this system, patients with a score of 2–3 points appear to benefit from surgical management, although this claim requires further verification. The four main surgical options for the treatment of PBSH are craniotomy, stereotactic hematoma puncture and drainage, endoscopic hematoma removal, and external ventricular drainage. Nevertheless, the management of PBSH still primarily involves conservative treatment methods and surgery is generally not recommended, according to current practice. However, the ongoing clinical trial, entitled Safety and Efficacy of Surgical Treatment in Severe Primary Pontine Hemorrhage Evacuation (STIPE), should provide additional evidence to support the surgical treatment of PBSH. Therefore, we advocate the update of epidemiological data and re-evaluation of PBSH treatment in a contemporary context.

NCyborg Project, a new stroke rehabilitation pattern based on brain computer interface (BCI) and brain-inspired intelligent robots, is set up by Tongji Hospital and BrainCo. We will briefly introduce this project in this paper.

Background: Antiplatelet therapy (APT) was prevalently being used in the prevention of vascular disease, but the influence of prior APT on the prognosis of patients with intracerebral hemorrhage (ICH) remains controversial. This meta-analysis was to explore the effects of prior APT on the prognosis of patients with primary ICH. Methods: PubMed and Embase were searched to identify the eligible studies. The studies comparing the mortality of ICH patients with or without prior APT were included. The quality of these studies was evaluated by the Newcastle–Ottawa quality assessment scale. The adjusted or unadjusted odds ratio (OR) for mortality between ICH patients with and without prior APT were pooled with 95% confidence interval (95% CI) as the effect of this meta-analysis. Results: Twenty-two studies fulfilled the inclusion criteria and exhibited high qualities. The pooled OR was 1.37 (95% CI: 1.13–1.66, P= 0.001) for univariate analysis and 1.41 (95% CI: 1.05–1.90, P= 0.024) for multivariate analysis. The meta-regression indicated that for each 1-day increase in the time of assessment, the adjusted OR for the mortality of APT patients decreased by 0.0049 (95% CI: 0.0006–0.0091, P= 0.026) as compared to non-APT patients. Conclusion: Prior APT was associated with high mortality in patients with ICH that might be attributed primarily to its strong effect on early time. Key words: Antiplatelet Therapy; Intracerebral Hemorrhage; Meta-analysis; Outcome

Background Increasing evidence suggests that fibroblast growth factor 19 (FGF19) is a regulator of glucose metabolism and may provide a new therapeutic target for type 1 diabetes (T1D). However, the clinical relevance of FGF19 in T1D remains unclear. In this study, we examined the relationship between the serum FGF19 concentration and T1D. Methods This study included 81 newly diagnosed T1D patients and 80 sex- and age-matched healthy controls. The correlation between the FGF19 concentration and clinical characteristics of T1D patients and healthy controls was investigated. Logistic regression analysis was performed to determine whether levels of FGF19 were independently associated with T1D. Results The fasting serum FGF19 levels in the T1D group were significantly lower than those in the control group [159.9 (100.0-272.7) vs. 205.0 (126.9-307.9) pg/mL, P=0.008]. In all subjects, serum FGF19 levels were negatively correlated with fasting blood glucose (FBG) (r=-0.192, P=0.015). In the control group, serum FGF19 levels were positively correlated with total cholesterol (TC) (r=0.338, P=0.002) and low-density lipoprotein cholesterol (LDL-c) (r=0.300, P=0.007). In addition to sex and body mass index (BMI), FGF19 was an independent impact factor for T1D [odds ratio (OR) =0.541, P=0.023; adjusted for sex, age, BMI, presence of hypertension, and presence of dyslipidemia]. Conclusions Low serum FGF19 level is associated with T1D, which could serve as a risk factor for T1D.

Objectives Currently, the clinical repair of sciatic nerve injury remains difficult. Previous studies have confirmed that transplantation of adipose tissue-derived stem cells promotes nerve regeneration and restoration at peripheral nerve injury sites. Methods In this study, adipose tissue-derived stem cells were induced to differentiate into neural progenitor cells, transfected with a green fluorescent protein-containing lentivirus, and then transplanted into the lesions of rats with sciatic nerve compression injury. Results Fluorescence microscopy revealed that the transplanted cells survived, migrated, and differentiated in rats. At two weeks post-operation, a large number of transplanted cells had migrated to the injured lesions; at six weeks post-operation, transplanted cells were visible around the injured nerve and several cells were observed to express a Schwann cell marker. Sciatic function index and electrophysiological outcomes of the transplantation group were better than those of the control group. Cell transplantation promoted the recovery of motor nerve conduction velocity and compound muscle action potential amplitude, and reduced gastrocnemius muscle atrophy. Conclusions Our experimental findings indicate that neural progenitor cells, differentiated from adipose tissue-derived stem cells, are potential seed stem cells that can be transplanted into lesions to treat sciatic nerve injury. This provides a theoretical basis for their use in clinical applications.

Neuroglobin is an endogenous neuroprotective protein, but the underlying neuroprotective mechanisms remain to be elucidated. Our previous yeast two-hybrid screening study identified that Dishevelled-1, a key hub protein of Wnt/&beta, Catenin signaling, is an interaction partner of Neuroglobin. In this study, we further examined the role of Neuroglobin in regulating Dishevelled-1 and the downstream Wnt/&beta, Catenin and NF&kappa, B signaling pathway. We found that Neuroglobin directly interacts with Dishevelled-1 by co-immunoprecipitation, and the two proteins are co-localized in both cytoplasma and nucleus of SK-N-SH cells. Moreover, the ectopic expression of Neuroglobin promotes the degradation of exogenous and endogenous Dishevelled-1 through the proteasomal degradation pathway. Furthermore, our results showed that Neuroglobin significantly inhibits the luciferase activity of Topflash reporter and the expression of &beta, Catenin mediated by Dishevelled-1 in SK-N-SH cells. In addition, we also documented that Neuroglobin enhances TNF-&alpha, induced NF&kappa, B activation via down-regulating Dishevelled-1. Finally, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assays showed that Neuroglobin is an important neuroprotectant that protects SK-N-SH cells from TNF-&alpha, induced decrease in cell viability. Taken together, these findings demonstrated that Neuroglobin functions as an important modulator of the Wnt/&beta, B signaling pathway through regulating Dishevelled-1.

Summary Aims To examine whether transplantation of adipose-derived stem cells (ADSCs) induces neural differentiation and improves neural function in a rat intracerebral hemorrhage (ICH) model. Methods Adipose-derived stem cells cells were isolated from inguinal fat pad of rat. ICH was induced by injection of collagenase type IV into the right basal ganglia of rat. Forty-eight hours after ICH, ADSCs cells (10 μL of 2–4 × 107 cells/mL) were injected into the right lateral cerebral ventricle. The differentiation of ADSCs was detected in vitro and in vivo. The neural function was evaluated with Zea Longa 5-grade scale at day 1, 3, 7, 14, or 28. Results Our data demonstrated that ADSCs differentiated into cells that shared the similarities of neurons or astrocytes in vitro. Transplantation of ADSCs decreased cell apoptosis and the transplanted ADSCs were able to differentiate into neuron-like and astrocyte-like cells around the hematoma, accompanied with upregulation of vascular endothelial growth factor expression and improvement of neural function. Conclusions Our data suggest that transplantation of ADSCs could be a therapeutic approach for ICH stroke.

Objective: Most patients with stroke casued by middle cerebral artery occlusion (MCAO) show cognitive deficit that is generally regarded as resulting from damage to the cerebral cortex rather than the hippocampus. Whether MCAO induces hippocampal damage and whether this contributes to the cognitive defects remains unclear. Here we investigate the hippocampal damage and its correlation to cognitive defects after exclusively unilateral MCAO and the underlying mechanism for that damage. Methods: Patients were assessed for hippocampal damage by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), and the Mini Mental-Status Evaluation (MMSE) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess for cognitive defects. Results: We provide the first evidence that patients with exclusively unilateral MCAO showed hippocampal damage characterized by an infarct-size–independent atrophy and alterations in neuronal and glial metabolites in the ipsilateral hippocampus, in parallel with cognitive impairment. Rodent MCAO also induced delayed shrinkage and pyramidal neuronal death in the ipsilateral hippocampus and an impairment of hippocampal-dependent spatial memory. Blocking Gap junctional communication (GJC) with carbenoxolone or downregulation of connexin43 (Cx43) significantly increased the survival of the pyramidal neurons in the ipsilateral hippocampus and improved behavioral scores. Furthermore, Cx43 heterozygous mice showed reduced shrinkage and metabolite abnormality in ipsilateral hippocampus after MCAO. Interpretation: Astroglial GJC plays a significant role in MCAO-induced remote hippocampal damage and cognitive impairment. It might be possible to improve the cognition in patients with MCAO by manipulating interastrocytic communication via the gap junction channels. ANN NEUROL 2011

Chronic infection by Helicobacter pylori is regarded as an etiological factor for vascular diseases. However, there are conflicting results on the relevance of chronic infection by Helicobacter pylori as a risk factor for ischemic stroke. The aim of our study was to investigate the association between Helicobacter pylori infection and ischemic stroke subtypes in Chinese.A total of 150 patients with ischemic stroke were enrolled in the patient group. Analyses were stratified for etiologic stroke subtypes according to 2007 modified Trial of Org 10172 in Acute Stroke Treatment criteria: 119 patients with atherothrombosis, 15 patients with cardioembolism, and 12 patients with small artery disease. One hundred and thirty-one control subjects without clinical and instrumental evidence of atherosclerotic diseases were randomly selected from health check-up center. The potential risk factors for Helicobacter pylori infection and traditional risk factors for ischemic stroke of all subjects were analyzed. The serum specific antibody IgG of Helicobacter pylori was detected by enzyme-linked immunosorbent assay. Conditional logistic regression was used to analyze the data.The Helicobacter pylori/IgG-positive rate in the patient group was higher than that in the healthy control group, but the difference was not statistically significant [67.3% versus 61.8%; odds ratio (OR) = 1.272; P = 0.336]. This result remained non-significant after adjustment for other established risk factors [OR = 1.222; 95% confidence interval (CI): 0.688-2.171; P = 0.494]. Subgroup analysis using univariate and multivariate analyses yielded similar results in all etiologic stroke subtypes (univariate analysis, atherothrombosis: OR = 1.368, 95%CI: 0.810-2.311, P = 0.241; cardioembolism: OR = 0.926, 95%CI:0.311-2.758, P = 0.890; small artery disease: OR = 1.852, 95%CI: 0.478-7.167, P = 0.366; multivariate analysis, atherothrombosis: OR = 1.385, 95%CI: 0.726-2.639, P = 0.323; cardioembolism: OR = 0.832, 95%CI: 0.236-2.932, P = 0.775; small artery disease: OR = 1.836, 95%CI: 0.396-8.503, P = 0.437).This case-control study does not reveal any strong association between chronic Helicobacter pylori infection and ischemic stroke. Large case-control prospective studies are required for further investigation of the potential association between Helicobacter pylori infection and ischemic stroke risk, particularly in certain subgroups.

Galectin-1, an endogenous mammalian lectin, has been implicated in a variety of CNS disorders. However, its role in cerebral ischemia is still elusive. In the present study, we investigated the effect of recombinant galectin-1 on production of astrocytic brain-derived neurotrophic factor (BDNF) and functional recovery following ischemia. Endogenous galectin-1 was found to be markedly upregulated, paralleled with increased astrocytic BDNF production under ischemic conditions both in vitro and in vivo. Administration of galectin-1 significantly enhanced the expression and secretion of astrocytic BDNF in dose dependent manner. Moreover, rats subjected to photochemical cerebral ischemia showed reduced neuronal apoptosis in ischemic boundary zone and improved functional recovery after brain infusion of galectin-1 (1 μg/days, 7 days). These results suggest that induction of BDNF in astrocytes by galectin-1 may be a promising intervention to attenuate brain damage after stroke.

To comprehensively evaluate the therapeutic effects on both functional and structural outcomes, we performed a meta-analysis of preclinical data on stem cell therapy in intracranial hemorrhage, thus providing optimal evidence and instruction for clinical translation. We searched online databases to identify eligible studies based on unmodified stem cell transplantation in intracranial hemorrhage (ICH). From each study, we extracted data regarding neurobehavioral and histological outcomes in order to analyze the comprehensive effective sizes according to the most important clinical parameters (seven indices) and to explore any potential correlation through meta-regression. We analyzed 40 eligible studies including 1021 animals and found a significant improvement in both behavioral and structural outcomes with the median effect size of 1.77 for modified Neurological Severity Score, 1.16 for the modified placement test, 1.82 for the rotarod test, and 1.24 for tissue loss reduction. The meta-regression results revealed that intracerebral administration was the most effective for behavioral and structural recovery post-ICH; mesenchymal stem cells shared comparable therapeutic effects with neural stem cells. Delayed therapy, applied more than 1 week after ICH, showed the greatest improvement of structural outcomes. Stem cell therapy showed significant improvement on behavioral and structural outcomes of ICH animals with relatively large effect sizes. However, the practical efficacy of the therapy is likely to be lower considering poor study quality and non-negligible publication bias. Further, future research should interpret animal results cautiously considering the limited internal and external validity when referring to the design of both animal studies and clinical trials. Electronic supplementary material The online version of this article (doi:10.1007/s12035-015-9441-6) contains supplementary material, which is available to authorized users.

Transplantation of neural stem cells (NSCs) to treat neurodegenerative disease shows promise; however, the clinical application of NSCs is limited by the invasive procurement and ethical concerns. Adipose-derived stem cells (ADSCs) are a source of multipotent stem cells that can self-renew and differentiate into various kinds of cells; this study intends to generate neurospheres from human ADSCs by culturing ADSCs on uncoated culture flasks in serum-free neurobasal medium supplemented with B27, basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF); the ADSCs-derived neurospheres were terminally differentiated after growth factor withdrawal. Expression of Nestin, NeuN, MAP2, and GFAP in ADSCs and terminally differentiated neurospheres was shown by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and immunocytochemistry; cell proliferation in neurospheres was evaluated by cell cycle analyses, immunostaining, and flow cytometry. These data strongly support the conclusion that human ADSCs can successfully differentiate into neurospheres efficiently on uncoated culture flasks, which present similar molecular marker pattern and proliferative ability with NSCs derived from embryonic and adult brain tissues. Therefore, human ADSCs may be an ideal alternative source of stem cells for the treatment of neurodegenerative diseases.

Neural stem cells (NSCs) can be isolated from nervous tissues or derived from embryonic stem cells. However, their procurement for clinical applications is limited, and there is a need for alternative types of cell that have NSCs properties. In the present study, the differentiation potential of rat adipose-derived stem cells (ADSCs) was evaluated by infecting these cells with a lentiviral vector-encoding green fluorescent protein (GFP). ADSCs transduced with lentivirus were able to generate NSC-like cells, without any effects on their growth, phenotype, and normal differentiation potential. NSC-like cells derived from ADSCs formed neurospheres and expressed high levels of the neural progenitor marker nestin. In the absence of selected growth factors, these neurospheres differentiated into neurons expressing NeuN and MAP2 and GFAP-expressing glia, as determined by immunocytochemistry, Western blotting, and quantitative real-time polymerase chain reaction. These results demonstrate that ADSCs can be induced to generate neurospheres that have NSC-like properties and may thus constitute a potential source of cells in stem cell therapy for neurological disorders.

ObjectivesCurrently, the clinical repair of sciatic nerve injury remains difficult. Previous studies have confirmed that transplantation of adipose tissue-derived stem cells promotes nerve regenera...