Although alpha-synuclein is general y thought to have a pathological role in Parkinson’s disease, accumulative evidence exists that alpha-synuclein has a neuroprotective effect. The aim of this study was to evaluate the effect of extracellular alpha-synuclein on dopaminergic cellsurvival. We assessed cellviability using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltertazolium bromide (MTT) assay both in undifferentiated SH-SY5Y (SHSY) cells and neuronal y-differentiated SH-SY5Y (ndSHSY) cells after 24 hour treatment with monomeric alpha-synuclein at various concentrations (0 [control], 50, 100 nmol/L, 1μmol/L). To determine whether cellviability assessed by MTT assay was affected by cellproliferation, 5-bromo-2'-deoxyuridine (BrdU) incorporation assay was per-formed. Level of both Akt and phosphorylated Akt was measured using western blot method in ndSHSY cells with or without 24 hour alpha-synuclein treatment. cellviability was increased in ndSHSY cells at the nanomolar concentration of alpha-synuclein, but not in SHSY cells. Proportion of BrdU-positive ndSHSY cells was decreased in alpha-synuclein-treated group compared with control group. Level of phosphorylated Akt in alpha-synuclein-treated group was higher compared with the control group. Our study shows that extracellular alpha-synuclein at nanomolar concentra-tion benefits dopaminergic cellsurvival via Akt pathway.

A preliminary clinical study by our group demonstrated Bushen Yisui Capsule (formerly cal ed Er-huang Formula) in combination with conventional therapy is an effective prescription for the treat-ment of multiple sclerosis. However, its effect on axonal injury during early multiple sclerosis re-mains unclear. In this study, a MOG 35-55-immunized C57BL/6 mouse model of experimental au-toimmune encephalomyelitis was intragastrical y administered Bushen Yisui Capsule. The results showed that Bushen Yisui Capsule effectively improved clinical symptoms and neurological function of experimental autoimmune encephalomyelitis. In addition, amyloid precursor protein expression was down-regulated and microtubule-associated protein 2 was up-regulated. Experimental findings indicate that the disease-preventive mechanism of Bushen Yisui Capsule in experimental autoim-mune encephalomyelitis was mediated by amelioration of axonal damage and promotion of rege-neration. But the effects of the high-dose Bushen Yisui Capsule group was not better than that of the medium-dose and low-dose Bushen Yisui Capsule group in preventing neurological dysfunction.

Because neurons are susceptible to oxidative damage and thioredoxin reductase 1 is extensively distributed in the central nervous system and has antioxidant properties, we speculated that the enzyme may be involved in the pathogenesis of Parkinson’s disease. A Parkinson’s disease model was produced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into C57BL/6 mice. Real-time reverse transcription-PCR, western blot analysis and colorimetric assay showed that the levels of thioredoxin reductase 1 mRNA and protein were decreased, along with a significant reduction in thioredoxin reductase activity, in the midbrain of Parkinson’s disease mice compared with normal mice. Immunohistochemical staining revealed that the number of thioredoxin reductase 1-positive neurons in the substantia nigra pars compacta of Parkinson’s disease mice was significantly decreased compared with normal mice. These experimental findings suggest that the expression of thioredoxin reductase 1 in the substantia nigra pars compacta of Parkinson’s disease mice is significantly decreased, and that the enzyme may be associated with disease onset.

Antiepileptic drugs are the preferred treatment approach for epileptic patients. However, informal treatment is important for intractable epilepsy. In this study, 500 epileptic patients were recruited from the General Hospital of Beijing Military Area Command of Chinese PLA during the period of October 2009 to January 2012. These involved patients that had been medical y treated for at least 1 year. Information on the initial treatment and changes to treatment regimens for each patient was col ected through questionnaires. The survey results showed that 52.3% of the epileptic patients searched for treatment after the first seizure, and the mean numbers of seizures was 12.8;59.8%of the epileptic patients were diagnosed at the first visit, and the mean onset time was 17 months after the first seizure. After diagnosis, patients were treated for an average of 20 days, and the median time was 1 day. Formal anti-epileptic drugs were selected as the first treatment regimen by 67.8%of patients, and 77.5%of these drugs were monotherapies. The mean and median numbers of seizure were respectively 36.9 and 3.0 times before the first regimen was changed. The regimen was changed within the first 6 months by 46.6% of patients, and after the first and second years of treatment, the proportions increased to 54.0%and 71.8%, respectively. In total, 78.5%of the regi-mens were changed to informal treatments. The informal treatment of epilepsy in China is common, being initiated by either patients or physicians. Enhancing epileptic treatment services in hospital, improving physicians’ professional quality, and strengthening health propaganda may promote the normalization of drug treatment of epilepsy in China.

Abnormal TAR DNA-binding protein 43 (TDP-43) inclusion bodies can be detected in the degener-ative neurons of amyotrophic lateral sclerosis. In this study, we induced chronic oxidative stress in-jury by applying malonate to cultured mouse cortical motor neurons. In the later stages of the ma-lonate insult, TDP-43 expression reduced in the nuclei and transferred to the cytoplasm. This was accompanied by neuronal death, mimicking the pathological changes in TDP-43 that are seen in patients with amyotrophic lateral sclerosis. Interestingly, in the early stages of the response to ma-lonate treatment, nuclear TDP-43 expression increased, and neurons remained relatively intact, without inclusion bodies or fragmentation. Therefore, we hypothesized that the increase of nuclear TDP-43 expression might be a pro-survival factor against oxidative stress injury. This hypothesis was confirmed by an in vitro transgenic experiment, in which overexpression of wild type mouse TDP-43 in cultured cortical motor neurons significantly reduced malonate-induced neuronal death. Our findings suggest that the loss of function of TDP-43 is an important cause of neuronal dege-neration, and upregulation of nuclear TDP-43 expression might be neuroprotective in amyotrophic lateral sclerosis.

Experimental al ergic encephalomyelitis is a mouse model of human multiple sclerosis with similar pathology and pathogenesis. Th1 cells play an important role in the pathogenesis of experimental al ergic encephalomyelitis. This study determined the potential effect of programmed celldeath 1 ligand 1 in the pathogenesis of experimental al ergic encephalomyelitis induced by injecting myelin oligodendrocyte glycoprotein, complete Freund’s adjuvant and Bordetel a pertussis toxin into C57BL/6J mice. Experimental al ergic encephalomyelitis mice developed disease and showed in-flammatory changes in the central nervous system by hematoxylin-eosin staining of spinal cord pathological sections, demyelination by Luxol fast-blue staining and clinical manifestations. The expression of programmed celldeath 1 ligand 1 in mice was detected by immunohistochemistry, flow cytometry and western blot analysis. The expression of programmed celldeath 1 ligand 1 in the spinal cord and splenocytes of mice was significantly increased compared with normal mice. Our findings suggest the involvement of programmed celldeath 1 ligand 1 in the pathogenesis of expe-rimental al ergic encephalomyelitis and suggest this should be studied in multiple sclerosis.

Human adipose tissues are an ideal source of stem cells. It is important to find inducers that can safely and effectively differentiate stem cells into functional neurons for clinical use. In this study, we investigate the use of Radix Angelicae Sinensis as an inducer of neuronal differentiation. Primary human adipose-derived stem cells were obtained from adult subcutaneous fatty tissue, then pre-induced with 10%Radix Angelicae Sinensis injection for 24 hours, and incubated in serum-free Dulbecco’s modified Eagle’s medium/Nutrient Mixture F-12 containing 40% Radix Angelicae Si-nensis to induce its differentiation into neuron-like cells. Butylated hydroxyanisole, a common in-ducer for neuronal differentiation, was used as the control. After human adipose-derived stem cells differentiated into neuron-like cells under the induction of Radix Angelicae Sinensis for 24 hours, the positive expression of neuron-specific enolase was lower than that of the butylated hydroxyani-sole-induced group, and the expression of glial fibril ary acidic protein was negative. After they were induced for 48 hours, the positive expression of neuron specific enolase in human adipose-derived stem cells was significantly higher than that of the butylated hydroxyanisole-induced group. Our experimental findings indicate that Radix Angelicae Sinensis can induce human adipose-derived stem celldifferentiation into neuron-like cells and produce less cytotoxicity.

Reward-based decision-making has been found to activate several brain areas, including the ven-trolateral prefrontal lobe, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and meso-limbic dopaminergic system. In this study, we observed brain areas activated under three degrees of uncertainty in a reward-based decision-making task (certain, risky, and ambiguous). The tasks were presented using a brain function audiovisual stimulation system. We conducted brain scans of 15 healthy volunteers using a 3.0T magnetic resonance scanner. We used SPM8 to analyze the location and intensity of activation during the reward-based decision-making task, with respect to the three conditions. We found that the orbitofrontal cortex was activated in the certain reward con-dition, while the prefrontal cortex, precentral gyrus, occipital visual cortex, inferior parietal lobe, ce-rebel ar posterior lobe, middle temporal gyrus, inferior temporal gyrus, limbic lobe, and midbrain were activated during the ‘risk’ condition. The prefrontal cortex, temporal pole, inferior temporal gyrus, occipital visual cortex, and cerebel ar posterior lobe were activated during ambiguous deci-sion-making. The ventrolateral prefrontal lobe, frontal pole of the prefrontal lobe, orbitofrontal cortex, precentral gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus, inferior parietal lo-bule, and cerebel ar posterior lobe exhibited greater activation in the‘risk’ than in the‘certain’ con-dition (P<0.05). The frontal pole and dorsolateral region of the prefrontal lobe, as wel as the ce-rebel ar posterior lobe, showed significantly greater activation in the ‘ambiguous’ condition com-pared to the ‘risk’ condition (P < 0.05). The prefrontal lobe, occipital lobe, parietal lobe, temporal lobe, limbic lobe, midbrain, and posterior lobe of the cerebel um were activated during deci-sion-making about uncertain rewards. Thus, we observed different levels and regions of activation for different types of reward processing during decision-making. Specifical y, when the degree of reward uncertainty increased, the number of activated brain areas increased, including greater ac-tivation of brain areas associated with loss.

Hyperbaric oxygen therapy has been widely applied and recognized in the treatment of brain injury;however, the correlation between the protective effect of hyperbaric oxygen therapy and changes of metabolites in the brain remains unclear. To investigate the effect and potential mechanism of hyperbaric oxygen therapy on cognitive functioning in rats, we established traumatic brain injury models using Feeney’s free fal ing method. We treated rat models with hyperbaric oxygen therapy at 0.2 MPa for 60 minutes per day. The Morris water maze test for spatial navigation showed that the average escape latency was significantly prolonged and cognitive function decreased in rats with brain injury. After treatment with hyperbaric oxygen therapy for 1 and 2 weeks, the rats’ spatial learning and memory abilities were improved. Hydrogen proton magnetic resonance spectroscopy analysis showed that the N-acetylaspartate/creatine ratio in the hippocampal CA3 region was sig-nificantly increased at 1 week, and the N-acetylaspartate/choline ratio was significantly increased at 2 weeks after hyperbaric oxygen therapy. Nissl staining and immunohistochemical staining showed that the number of nerve cells and Nissl bodies in the hippocampal CA3 region was significantly increased, and glial fibril ary acidic protein positive cells were decreased after a 2-week hyperbaric oxygen therapy treatment. Our findings indicate that hyperbaric oxygen therapy significantly im-proves cognitive functioning in rats with traumatic brain injury, and the potential mechanism is me-diated by metabolic changes and nerve cellrestoration in the hippocampal CA3 region.

Approximately 50-70% of patients experience incision-induced mechanical nociception after sur-gery. However, the mechanism underlying incision-induced mechanical nociception is stil unclear. Interleukin-10 and brain-derived neurotrophic factor are important pain mediators, but whether in-terleukin-10 and brain-derived neurotrophic factor are involved in incision-induced mechanical no-ciception remains uncertain. In this study, forty rats were divided randomly into the incision surgery (n=32) and sham surgery (n=8) groups. Plantar incision on the central part of left hind paw was performed under anesthesia in rats from the surgery group. Rats in the sham surgery group re-ceived anesthesia, but not an incision. Von Frey test results showed that, compared with the sham surgery group, incision surgery decreased the withdrawal threshold of rats at 0.5, 3, 6 and 24 hours after incision. Immunofluorescence staining in the dorsal root ganglia of the spinal cord (L 3-5 ) showed that interleukin-10 and brain-derived neurotrophic factor were expressed mainly on smal-and medium-sized neurons (diameter<20μm and 20-40μm) and satel ite cells in the dorsal root ganglia of the spinal cord (L 3-5 ) in the sham surgery group. By contrast, in the surgery group, high expression of interleukin-10 and brain-derived neurotrophic factor appeared in large-sized neurons (diameter>40μm) at 6 and 24 hours after incision surgery, which corresponded to the decreased mechanical withdrawal threshold of rats in the surgery group. These experimental findings suggest that expression pattern shift of interleukin-10 and brain-derived neurotrophic factor induced by inci-sion surgery in dorsal root ganglia of rats was closely involved in lowering the threshold to me-chanical stimulus in the hind paw fol owing incision surgery. Pain-related mediators induced by in-cision surgery in dorsal root ganglia of rats possibly underlie mechanical nociception in ipsilateral hind paws.