Acupuncture has been used to treat neuropathic pain for a long time, but its mechanisms of action remain unknown. In this study, we observed the effects of electroacupuncture and manual acu-puncture on neuropathic pain and on ephrin-B/EphB signaling in rats models of chronic constriction injury-induced neuropathic pain. The results showed that manual acupuncture and elec-puncture significantly reduced mechanical hypersensitivity fol owing chronic constriction injury, es-pecial y electroacupuncture treatment. Real-time PCR results revealed that ephrin-B1/B3 and EphB1/B2 mRNA expression levels were significantly increased in the spinal dorsal horns of chronic constriction injury rats. Electroacupuncture and manual acupuncture suppressed the high sion of ephrin-B1 mRNA, and elevated EphB3/B4 mRNA expression. Electroacupuncture signifi-cantly enhanced the mRNA expression of ephrin-B3 and EphB3/B6 in the dorsal horns of neuro-pathic pain rats. Western blot results revealed that electroacupuncture in particular, and manual acupuncture, significantly up-regulated ephrin-B3 protein levels in rat spinal dorsal horns. The re-sults of this study suggest that acupuncture could activate ephrin-B/EphB signaling in neuropathic pain rats and improve neurological function.

Stroke remains a worldwide health problem. Salvianolate exerts a protective effect in various mi-crocirculatory disturbance-related diseases, but studies of the mechanisms underlying its protective action have mainly focused on the myocardium, whereas little research has been carried out in brain tissue fol owing ischemia-reperfusion. We assessed the neuroprotective effects of salvianolate in a rat model of cerebral ischemia-reperfusion injury induced using the suture method. At onset and 24 and 48 hours after reperfusion, rats were intraperitoneal y injected with salvianolate (18 mg/kg) or saline. Neurological deficit scores at 72 hours showed that the neurological functions of rats that had received salvianolate were significantly better than those of the rats that had received saline. 2,3,5-Triphenyltetrazolium chloride was used to stain cerebral tissue to determine the extent of the infarct area. A significantly smal er infarct area and a significantly lower number of apoptotic cel s were observed after treatment with salvianolate compared with the saline treatment. Expression of heat shock protein 22 and phosphorylated protein kinase B in ischemic brain tissue was significantly greater in rats treated with salvianolate compared with rats treated with saline. Our findings suggest that salvianolate provides neuroprotective effects against cerebral ischemia-reperfusion injury by upregulating heat shock protein 22 and phosphorylated protein kinase B expression.

The death of retinal ganglion cel s is a hal mark of many optic neurodegenerative diseases such as glaucoma and retinopathy. Oxidative stress is one of the major reasons to cause the cel death. Oligomeric proanthocyanidin has many health beneficial effects including antioxidative and neuro-protective actions. Here we tested whether oligomeric proanthocyanidin may protect retinal glion cel s against oxidative stress induced-apoptosis in vitro. Retinal ganglion cel s were treated with hydrogen peroxide with or without oligomeric proanthocyanidin. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that treating retinal ganglion cel line RGC-5 cel s with 20 μmol/L oligomeric proanthocyanidin significantly decreased the hydrogen peroxide (H 2 O 2 ) induced death. Results of flow cytometry and Hoechst staining demonstrated that the death of RGC-5 cel s was mainly caused by cel apoptosis. We further found that expression of pro-apoptotic Bax and caspase-3 were significantly decreased while anti-apoptotic Bcl-2 was greatly increased in H 2 O 2 damaged RGC-5 cel s with oligomeric proanthocyanidin by western blot assay. Furthermore, in retinal explant culture, the number of surviving retinal ganglion cel s in H 2 O 2-damaged retinal ganglion cel s with oligomeric proanthocyanidin was significantly increased. Our studies thus demonstrate that oligomeric proanthocyanidin can protect oxidative stress-injured retinal ganglion cel s by inhibiting apoptotic process.

Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are stil unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cel s and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cel s were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibril ary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibril ary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibril ary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cel s. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

The traditional Chinese medicine Buyang Huanwu Decoction has been shown to improve the neu-rological function of patients with stroke. However, the precise mechanisms underlying its effect remain poorly understood. In this study, we established a rat model of cerebral ischemia by middle cerebral artery occlusion and intragastrical y administered 5 g/kg Buyang Huanwu Decoction, once per day, for 1, 7, 14 and 28 days after cerebral ischemia. Immunohistochemical staining revealed a number of cel s positive for the neural stem cel marker nestin in the cerebral cortex, the subven-tricular zone and the ipsilateral hippocampal dentate gyrus in rat models of cerebral ischemia. Buyang Huanwu Decoction significantly increased the number of cel s positive for 5-bromodeoxyuridine (BrdU), a cel proliferation-related marker, microtubule-associated protein-2, a marker of neuronal differentiation, and growth-associated protein 43, a marker of synaptic plasticity in the ischemic rat cerebral regions. The number of positive cel s peaked at 14 and 28 days after intragastric administration of Buyang Huanwu Decoction. These findings suggest that Buyang Huanwu Decoction can promote the proliferation and differentiation of neural stem cel s and hance synaptic plasticity in ischemic rat brain tissue.

The cerebral ischemia-reperfusion model was established using the suture occlusion method, and rats were intraperitoneal y given 8 mL/kg Danhong injection once a day prior to model establishment. Rat brain tissues were harvested at 6, 24, 48, 72 hours after reperfusion. Immunohistochemical staining showed that transforming growth factor-β1 expression increased, while Golgi matrix protein GM130 expression decreased after cerebral ischemia-reperfusion. Danhong injection was shown to significantly up-regulate the expression of transforming growth factor-β1 and GM130, and expres-sion levels peaked at 7 days after reperfusion. At 7 days after cerebral ischemia-reperfusion, Golgi morphology was damaged in untreated rats, while Golgi morphology breakage was not observed after intervention with Danhong injection. These experimental findings indicate that Danhong injec-tion can up-regulate the expression of transforming growth factor-β1 and GM130, and maintain Golgi stability, thus playing a neuroprotective role in rats after cerebral ischemia-reperfusion.

Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance fol owing ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions fol owing cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the de-crease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpy-ruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor fol owing cerebral ischemia may be involved in the development of glucose intolerance.

Metformin may reduce food intake and body weight, but the anorexigenic effects of metformin are stil poorly understood. In this study, Sprague-Dawley rats were administered a single intracere-broventricular dose of metformin and compound C, in a broader attempt to investigate the regula-tory effects of metformin on food intake and to explore the possible mechanism. Results showed that central administration of metformin significantly reduced food intake and body weight gain, par-ticularly after 4 hours. A reduction of neuropeptide Y expression and induction of AMP-activated protein kinase phosphorylation in the hypothalamus were also observed 4 hours after metformin administration, which could be reversed by compound C, a commonly-used antagonist of AMP-activated protein kinase. Furthermore, metformin also improved lipid metabolism by reducing plasma low-density lipoprotein. Our findings suggest that under normal physiological conditions, central regulation of appetite by metformin is related to a decrease in neuropeptide Y gene expres-sion, and that the activation of AMP-activated protein kinase may simply be a response to the anorexigenic effect of metformin.

We selected 106 hemiplegic patients with shoulder pain hospitalized after stroke from three hospit-als in Nanjing, China between February 2007 and January 2012. Al patients had complete clinical data sets and accounted for 45.5% of the inpatients because of stroke. Results showed that the number of patients with hemiplegic shoulder pain post stroke increased yearly, attacking mainly males 50-69 years of age. Of 106 patients, there were 60 cases (56.6%) of adhesive capsulitis, 19 (17.9%) of shoulder subluxation, 14 (13.2%) of complex regional pain syndrome, and 13 (12.6%) of central pain. The main symptoms were shoulder pain (100%), limit of shoulder mobility (98.1%), and adhesion of the scapula (56.6%). MRI of the shoulder showed tendon and ligament lesions (57.1%) and rotator cuff tear (38.1%). 53.8%of central pain was related to the thalamus, in addition to the basal ganglia, brain stem, and cerebel opontine angle. Shoulder pain, upper limb motor function, and function independence were significantly improved after comprehensive rehabilitation. In par-ticular, electroacupuncture based on basic physical therapy exhibited efficacy on shoulder tion and complex regional pain syndrome. Multiple linear regression results showed a negative re-lationship of efficacy of pain management with the attack period of shoulder pain, involvement of the posterior limb of the internal capsule, and duration between onset and rehabilitation treatment, but a positive correlation with pain-related education, pain regression period, and pain diagnosis.