Several studies have demonstrated that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. It is hypothesized that citalopram, a selective serotonin reuptake inhibitor, can promote the neuronal differentiation of adult bone marrow mesenchymal stem cells. Citalopram strongly enhanced neuronal characteristics of the cells derived from bone marrow mesenchymal stem cells. The rate of cell death was decreased in citalopram-treated bone marrow mesenchymal stem cells than in control cells in neurobasal medium. In addition, the cumulative population doubling level of the citalopram-treated cells was signiifcantly increased compared to that of control cells. Also BrdU incorporation was elevated in citalopram-treated cells. These ifndings suggest that citalopram can improve the neuronal-like cell differentiation of bone marrow mesenchymal stem cells by increasing cell proliferation and survival while maintaining their neuronal characteristics.

Here, we administered repeated-pulse transcranial magnetic stimulation to healthy people at the left Guangming (GB37) and a mock point, and calculated the sample entropy of electroencephalo-gram signals using nonlinear dynamics. Additionally, we compared electroencephalogram sample entropy of signals in response to visual stimulation before, during, and after repeated-pulse tran-scranial magnetic stimulation at the Guangming. Results showed that electroencephalogram sample entropy at left (F3) and right (FP2) frontal electrodes were significantly different depending on where the magnetic stimulation was administered. Additionally, compared with the mock point, electroencephalogram sample entropy was higher after stimulating the Guangming point. When visual stimulation at Guangming was given before repeated-pulse transcranial magnetic stimula-tion, signiifcant differences in sample entropy were found at ifve electrodes (C3, Cz, C4, P3, T8) in parietal cortex, the central gyrus, and the right temporal region compared with when it was given after repeated-pulse transcranial magnetic stimulation, indicating that repeated-pulse transcranial magnetic stimulation at Guangming can affect visual function. Analysis of electroencephalogram revealed that when visual stimulation preceded repeated pulse transcranial magnetic stimulation, sample entropy values were higher at the C3, C4, and P3 electrodes and lower at the Cz and T8 electrodes than visual stimulation followed preceded repeated pulse transcranial magnetic stimula-tion. The ifndings indicate that repeated-pulse transcranial magnetic stimulation at the Guangming evokes different patterns of electroencephalogram signals than repeated-pulse transcranial mag-netic stimulation at other nearby points on the body surface, and that repeated-pulse transcranial magnetic stimulation at the Guangming is associated with changes in the complexity of visually evoked electroencephalogram signals in parietal regions, central gyrus, and temporal regions.

The transcription factor early growth response protein 3 (EGR3) is involved in schizophrenia. We developed a putative rat model of schizophrenia by transfecting lentiviral particles carrying the Egr3 gene into bilateral hippocampal dentate gyrus. We assessed spatial working memory using the Morris water maze test, and neuronal metabolite levels in bilateral hippocampus and thalamus were determined by 3.0 T proton magnetic resonance spectroscopy. Choline content was significantly greater in the hippocampus after transfection, while N-acetylaspartate and the ratio of N-acetylaspartate to creatine/phosphocreatine in the thalamus were lower than in controls. This study is the first to report evaluation of brain metabolites using 3.0 T proton magnetic resonance spectroscopy in rats transfected with Egr3, and reveals metabolic abnormalities in the hippocampus and thalamus in this putative model of schizophrenia.

Hemiplegia caused by stroke indicates dysfunction of the network between the brain and limbs, namely col ateral shock in the brain. Contralateral needling is the insertion of needles into acupoints on the relative healthy side of the body to treat diseases such as apoplexy. However, there is little wel-designed and control ed clinical evidence for this practice. This study investigated whether contralateral needling could treat hemiplegia after acute ischemic stroke in 106 randomly selected patients with acute ischemic stroke. These patients were randomly assigned to three groups:45 in the contralateral needling group, receiving acupuncture on the unaffected limbs; 45 in the tional acupuncture group, receiving acupuncture on the hemiplegic limbs; and 16 in the control group, receiving routine treatments without acupuncture. Acupuncture at acupoints Chize (LU5) in the upper limb and Jianliao (TE14) in the lower limb was performed for 45 minutes daily for 30 consecutive days. The therapeutic effective rate, Neurological Deficit Score, Modified Barthel Index and Fugl-Meyer Assessment were evaluated. The therapeutic effective rate of contralateral needl-ing was higher than that of conventional acupuncture (46.67% vs. 31.11%, P < 0.05). The neuro-logical deficit score of contralateral needling was significantly decreased compared with conven-tional acupuncture (P < 0.01). The Modified Barthel Index and Fugl-Meyer Assessment score of contralateral needling increased more significantly than those of conventional acupuncture (both P<0.01). The present findings suggest that contralateral needling unblocks col aterals and might be more effective than conventional acupuncture in the treatment of hemiplegia fol owing acute ischemic stroke.

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.

Ototoxic drug-induced apoptosis of inner ear cel s has been shown to be associated with calpain expression. Cisplatin has severe ototoxicity, and can induce cochlear cel apoptosis. This study assumed that cisplatin activated calpain expression in apoptotic cochlear cel s. A mouse model of cisplatin-induced ototoxicity was established by intraperitoneal injection with cisplatin (2.5, 3.5, 4.5, 5.5 mg/kg). Immunofluorescence staining, image analysis and western blotting were used to detect the expression of calpain 1 and calpain 2 in the mouse cochlea. At the same time, the auditory brainstem response was measured to observe the change in hearing. Results revealed that after intraperitoneal injection with cisplatin for 5 days, the auditory brainstem response threshold shifts increased in mice. Calpain 1 and calpain 2 expression significantly increased in outer hair cel s, the spiral ganglion and stria vascularis. Calpain 2 protein expression markedly increased with an in-creased dose of cisplatin. Results suggested that calpain 1 and calpain 2 mediated cispla-tin-induced ototoxicity in BALB/c mice. During this process, calpain 2 plays a leading role.

A previous study of European Caucasian patients with sporadic amyotrophic lateral sclerosis demonstrated that a polymorphism in the microtubule-associated protein Tau (MAPT) gene was significantly associated with sporadic amyotrophic lateral sclerosis pathogenesis. Here, we tested this association in 107 sporadic amyotrophic lateral sclerosis patients and 100 healthy controls from the Chinese Han population. We screened the mutation-susceptible regions of MAPT-the 3′and 5′untranslated regions as wel as introns 9, 10, 11, and 12-by direct sequencing, and identified 33 genetic variations. Two of these, 105788 A>G in intron 9 and 123972 T>A in intron 11, were not present in the control group. The age of onset in patients with the 105788 A>G and/or the 123972 T>A variant was younger than that in patients without either genetic variation. Moreover, the pa-tients with a genetic variation were more prone to bulbar palsy and breathing difficulties than those with the wild-type genotype. This led to a shorter survival period in patients with a MAPT genetic variant. Our study suggests that the MAPT gene is a potential risk gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population.

Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are stil unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cel ular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/tyrosine kinase activity is able to modulate cel signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebel um and liver of the same animals. We demonstrated that atorvastatin treatment (80 mg/day for 14.5 months) to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebel um. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as wel as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not associated with higher oxidative/nitrosative stress levels. We hypothesize that biliverdin reductase-A-dependent inducible nitric oxide synthase regulation strongly contributes to the cognitive improvement observed fol owing atorvastatin treatment.

Drug treatment, electric stimulation and decimeter wave therapy have been shown to promote the repair and regeneration of the peripheral nerves at the injured site. This study prepared a Mackin-non’s model of rat sciatic nerve compression. Electric stimulation was given immediately after neurolysis, and decimeter wave radiation was performed at 1 and 12 weeks post-operation. Histo-logical observation revealed that intraoperative electric stimulation and decimeter wave therapy could improve the local blood circulation of repaired sites, al eviate hypoxia of compressed nerves, and lessen adhesion of compressed nerves, thereby decreasing the formation of new entrapments and enhancing compressed nerve regeneration through an improved microenvironment for rege-neration. Immunohistochemical staining results revealed that intraoperative electric stimulation and decimeter wave could promote the expression of S-100 protein. Motor nerve conduction velocity and amplitude, the number and diameter of myelinated nerve fibers, and sciatic functional index were significantly increased in the treated rats. These results verified that intraoperative electric stimulation and decimeter wave therapy contributed to the regeneration and the recovery of the functions in the compressed nerves.

C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene is a risk factor for stroke, suggesting that widespread detection could help to prevent stroke. DNA from 70 stroke pa-tients and 70 healthy controls was extracted from saliva using a magnetic nanoparticles-based method and from blood using conventional methods. Real-time PCR results revealed that the C677T polymorphism was genotyped by PCR using DNA extracted from both saliva and blood samples. The genotype results were confirmed by gene sequencing, and results for saliva and blood samples were consistent. The mutation TT genotype frequency was significantly higher in the stroke group than in controls. Homocysteine levels were significantly higher than controls in both TT genotype groups. Therefore, this noninvasive magnetic nanoparticles-based method using saliva samples could be used to screen for the MTHFR C677T polymorphism in target populations.

This is an expert consensus on the evaluation and treatment of thoracolumbar spinal injury, estab-lished from February 2009 to July 2010. The expert consensus consists mainly of six parts with a total of 54 recommendations including the overview (one item);pre-hospital care (one item);evalu-ation and diagnosis (13 items);treatment (23 items); prevention and treatment of major complica-tions (12 items);and rehabilitation (four items). This is the first time that Chinese experts have pub-lished a consensus on spine and spinal cord injury. The expert consensus was established based on Delphi methods, literature analysis, and clinical experiences. Each recommendation is supported by and was interpreted using multi-level evidences. The level of agreement with the recommenda-tion among the panel members was assessed as either low, moderate, or strong. Each panel member was asked to indicate his or her level of agreement on a 5-point scale, with “1” corre-sponding to neutrality and“5”representing maximum agreement. Scores were aggregated across the panel members and an arithmetic mean was calculated. This mean score was then translated into low, moderate, or strong. After al of the votes were col ected and calculated, the results showed no low-level recommendations, 10 moderate-level recommendations, and 44 strong-level recom-mendations. An expert consensus was reached and was recognized by Chinese spine surgeons. Wide-scale adoption of these recommendations is urgent in the management of acute thoracol-umbar spine and spinal cord injury in a broader attempt to create a standard evaluation and treat-ment strategy for acute thoracolumbar spine and spinal cord injury in China.

It remains unclear whether spinal cord ischemia-reperfusion injury caused by ischemia and other non-mechanical factors can be monitored by somatosensory evoked potentials. Therefore, we monitored spinal cord ischemia-reperfusion injury in rabbits using somatosensory evoked potential detection technology. The results showed that the somatosensory evoked potential latency was significantly prolonged and the amplitude significantly reduced until it disappeared during the period of spinal cord ischemia. After reperfusion for 30-180 minutes, the amplitude and latency began to gradual y recover; at 360 minutes of reperfusion, the latency showed no significant difference compared with the pre-ischemic value, while the somatosensory evoked potential amplitude in-creased, and severe hindlimb motor dysfunctions were detected. Experimental findings suggest that changes in somatosensory evoked potential latency can reflect the degree of spinal cord ischemic injury, while the amplitude variations are indicators of the late spinal cord reperfusion injury, which provide evidence for the assessment of limb motor function and avoid iatrogenic spinal cord injury.

The automatic detection and identification of electroencephalogram waves play an important role in the prediction, diagnosis and treatment of epileptic seizures. In this study, a nonlinear dynamics index-approximate entropy and a support vector machine that has strong generalization ability were applied to classify electroencephalogram signals at epileptic interictal and ictal periods. Our aim was to verify whether approximate entropy waves can be effectively applied to the automatic real-time detection of epilepsy in the electroencephalogram, and to explore its generalization ability as a classifier trained using a nonlinear dynamics index. Four patients presenting with partial epi-leptic seizures were included in this study. They were al diagnosed with neocortex localized epi-lepsy and epileptic foci were clearly observed by electroencephalogram. The electroencephalogram data form the four involved patients were segmented and the characteristic values of each segment, that is, the approximate entropy, were extracted. The support vector machine classifier was con-structed with the approximate entropy extracted from one epileptic case, and then electroence-phalogram waves of the other three cases were classified, reaching a 93.33%accuracy rate. Our findings suggest that the use of approximate entropy al ows the automatic real-time detection of electroencephalogram data in epileptic cases. The combination of approximate entropy and support vector machines shows good generalization ability for the classification of electroencephalogram signals for epilepsy.

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.

X-linked methyl-CpG binding protein 2 mutations can induce symptoms similar to those of Parkin-son’s disease and dopamine metabolism disorders, but the specific role of X-linked methyl-CpG binding protein 2 in the pathogenesis of Parkinson’s disease remains unknown. In the present study, we used 6-hydroxydopamine-induced human neuroblastoma cel (SH-SY5Y cel s) injury as a cel model of Parkinson’s disease. The 6-hydroxydopamine (50 μmol/L) treatment decreased protein levels for both X-linked methyl-CpG binding protein 2 and tyrosine hydroxylase in these cel s, and led to cel death. However, overexpression of X-linked methyl-CpG binding protein 2 was able to ameliorate the effects of 6-hydroxydopamine, it reduced 6-hydroxydopamine-induced apoptosis, and increased the levels of tyrosine hydroxylase in SH-SY5Y cel s. These findings suggesting that X-linked methyl-CpG binding protein 2 may be a potential therapeutic target for the treatment of Parkinson’s disease.

Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute ce-rebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms of hypoxic preconditioning in relation to its effects on angiogenesis, we in-duced a photochemical model of cerebral infarction in an inbred line of mice (BALB/c). Mice were then exposed to hypoxic preconditioning 30 minutes prior to model establishment. Results showed significantly increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra at 24 and 72 hours post infarction, mainly in neurons and vascular endothelial cells. Hy-Hypoxic preconditioning increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra and the expression of vascular endothelial growth factor was positively related to that of CD31. Moreover, hypoxic preconditioning reduced the infarct volume and improved rological function in mice. These findings indicate that the protective role of hypoxic preconditioning in acute cerebral infarction may possibly be due to an increase in expression of vascular endothelial growth factor and CD31 in the ischemic penumbra, which promoted angiogenesis.

Length and thickness of 152 corpus cal osa were measured in neonates within 24 hours of birth. Using ultrasonic diagnostic equipment with a neonatal brain-specific probe, corpus cal osum length and thickness of the genu, body, and splenium were measured on the standard mid-sagittal plane, and the anteroposterior diameter of the genu was measured in the coronal plane. Results showed that corpus cal osum length as wel as thickness of the genu and splenium increased with gesta-tional age and birth weight, while other measures did not. These three factors on the standard mid-sagittal plane are therefore likely to be suitable for real-time evaluation of corpus cal osum de-velopment in premature infants using cranial ultrasound. Further analysis revealed that thickness of the body and splenium and the anteroposterior diameter of the genu were greater in male infants than in female infants, suggesting that there are sex differences in corpus cal osum size during the neonatal period. A second set of measurements were taken from 40 premature infants whose ges-tational age was 34 weeks or less. Corpus cal osum measurements were corrected to a gestational age of 40 weeks, and infants were grouped for analysis depending on the outcome of a neonatal behavioral neurological assessment. Compared with infants with a normal neurological assessment, corpus cal osum length and genu and splenium thicknesses were less in those with abnormalities, indicating that corpus cal osum growth in premature infants is associated with neurobehavioral de-velopment during the early extrauterine stage.

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.

Changes in neurotransmitter levels in the brain play an important role in epilepsy-like attacks after pregnancy-induced preeclampsia-eclampsia. Metabotropic glutamate receptor 1 participates in the onset of lipid metabolism disorder-induced preeclampsia. Pregnant rats were fed with a high-fat diet for 20 days. Thus, these pregnant rats experienced preeclampsia-like syndromes such as tension and proteinuria. Simultaneously, metabotropic glutamate receptor 1 mRNA and protein ex-pressions were upregulated in the rat hippocampus. These findings indicate that increased sion of metabotropic glutamate receptor 1 promotes the occurrence of high-fat diet-induced preec-lampsia in pregnant rats.

Expression of miR-137 is downregulated in brain tissue from patients with depression and suicidal behavior, and is also downregulated in peripheral blood from stroke patients. However, it is not yet known if miR-137 acts as a bridge between stroke and depression. To test this, we used middle cerebral artery occlusion and chronic mild stress to establish a post-stroke depression model in rats. Compared with controls, we found significantly lower miR-137 levels in the brain and peripheral blood from post-stroke depression rats. Injection of a miR-137 antagonist into the brain ventricles upregulated miR-137 levels, and improved behavioral changes in post-stroke depression rats. Lu-ciferase assays showed miR-137 bound to the 3′UTR of Grin2A, regulating Grin2A expression in a neuronal cel line. Grin2A gene overexpression in the brain of post-stroke depression rats, noticea-bly suppressed the inhibitory effect of miR-137 on post-stroke depression. Overal , our results show that miR-137 suppresses Grin2A protein expression through binding to Grin2A mRNA, thereby ex-erting an inhibitory effect on post-stroke depression. Our results offer a new therapeutic direction for post-stroke depression.