A brain-machine interface (BMI) has recently been introduced to research a reliable control of machine from the brain information processing through single neural spikes in motor brain areas for paralyzed individuals. Small, wireless, and implantable BMI system should be developed to decode movement information for classifications of neural activities in the brain. In this paper, we have developed a totally implantable wireless neural signal transmission system (TiWiNets) combined with advanced digital signal processing capable of implementing a high performance BMI system. It consisted of a preamplifier with only 2 operational amplifiers (op-amps) for each channel, wireless bluetooth module (BM), a Labview-based monitor program, and 16 bit-RISC microcontroller. Digital finite impulse response (FIR) band-pass filter based on windowed sinc method was designed to transmit neural signals corresponding to the frequency range of 400 Hz to 1.5 kHz via wireless BM, measuring over -48 dB attenuated in the other frequencies. Less than +/-2% error by inputting a sine wave at pass-band frequencies for FIR algorithm test was obtained between simulated and measured FIR results. Because of the powerful digital FIR design, the total dimension could be dramatically reduced to 23x27x4 mm including wireless BM except for battery. The power isolation was built to avoid the effect of radio-frequency interference on the system as well as to protect brain cells from system damage due to excessive power dissipation or external electric leakage. In vivo performance was evaluated in terms of long-term stability and FIR algorithm for 4 months after implantation. Four TiWiNets were implanted into experimental animals' brains, and single neural signals were recorded and analyzed in real time successfully except for one due to silicon- coated problem. They could control remote target machine by classify neural spike trains based on decoding technology. Thus, we concluded that our study could fulfill in vivo needs to study various single neuron-movement relationships in diverse fields of BMI.
Automatic Data Processing ; Brain ; Brain-Computer Interfaces ; Neural Prostheses ; Organothiophosphorus Compounds ; Signal Processing, Computer-Assisted ; Silanes

Peripheral nerve injuries are a commonly encountered clinical problem and often result in a chronic pain and severe functional deficits. c-Fos expression is sometimes used as a marker of increased neuronal activity. We have developed herbal bath "HAC" for pain control using the following herbs: Harpagophytum procumbens, Atractylodes japonica, and Corydalis tuber. In the present study, we investigated the effects of herbal bath "HAC" on the recovery rate of the locomotor function and the expression of c-Fos in the ventrolateral periaqueductal gray (vlPAG) region of brain following sciatic crushed nerve injury in rats. Walking track analysis for the evaluation of functional recovery and immunohistochemistry for the c-Fos expression were used for this study. In the present results, characteristic gait change with dropping of the sciatic function index (SFI) was observed and c-Fos expression in the vlPAG was suppressed following sciatic crushed nerve injury in rats. Immersion into herbal bath "HAC" enhanced SFI value and restored c-Fos expression in the vlPAG to the control value. These results suggest that herbal bath "HAC" might activate neurons in the vlPAG, and it facilitates functional recovery from peripheral nerve injury. Here we showed that herbal bath "HAC" could be used as a new therapeutic intervention for pain control and functional recovery from peripheral nerve injury.
Animals ; Atractylodes ; Baths ; Brain ; Chronic Pain ; Corydalis ; Gait ; Harpagophytum ; Immersion ; Immunohistochemistry ; Neurons ; Periaqueductal Gray ; Peripheral Nerve Injuries ; Rats ; Track and Field ; Walking

Fucoidan, a sulfated polyanionic polymer of L-fucose, is obtained from brown marine macroalgae. In the present study, neuroprotective effect of fucoidan against N-methyl- D-aspartate (NMDA)-induced excitotoxicity in the hippocampus was investigated. The patch clamp study revealed that fucoidan significantly inhibited NMDA receptor-activated ion current in the acutely dissociated hippocampal CA1 neurons. In an organotypic hippocampal slice culture, fucoidan inhibited NMDA-induced neuronal cell death in a dose-dependent manner. The present study showed that fucoidan possesses a neuroprotective effect against NMDA-induced excitotoxicity, and that the suppressive effect of fucoidan on the NMDA-induced ion current can be suggested as being the underlying neuroprotective mechanism of fucoidan.
Animals ; Cell Death ; D-Aspartic Acid ; Hippocampus ; N-Methylaspartate ; Neurons ; Neuroprotective Agents ; Polymers ; Polysaccharides ; Rats ; Seaweed

Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been implicated in the growth inhibition of a number of cancer cells. In the present study, we investigated the antitumor effect of the PPARgamma agonist rosiglitazone in U87MG human glioma cells. Rosiglitazone treatment in vitro reduced cell proliferation without induction of cell death in a dose- and time-dependent manner. Rosiglitazone decreased cell migration and mRNA level of MMP-9. Rosiglitazone treatment also induced marked changes in glioma cell morphology. Oral administration of rosiglitazone in animals with subcutaneous U87MG glioma cells reduced tumor volume. Subsequent tumor tissue analysis showed that rosiglitazone decreased the number of PCNA-positive staining cells and MMP-9 expression and induced apoptosis of tumor cells. These data suggest that rosiglitazone exerts antineoplastic effect in U87MG cells and may serve as potential therapeutic agent for malignant human gliomas.
Administration, Oral ; Animals ; Apoptosis ; Cell Death ; Cell Movement ; Cell Proliferation ; Glioma ; Humans ; Peroxisomes ; PPAR gamma ; RNA, Messenger ; Thiazolidinediones ; Tumor Burden

The aim of this study is to verify the feasibility of control of one-dimensional (1-D) rotating machine using neural activities of Prefrontal cortex (PFC) in a BCI system. In this study, adult male Sprague-Dawley rats received bilateral implantation of recording micro-electrodes in PFC area. The spontaneous activities of a pair of PFC neurons of water-deprived rats were encoded and converted through a triple-step threshold comparator algorithm to three commands for one-dimensional movement control of a robotic wheel for accessing water. Averaged activities of two PFC neurons were quantized in every 200 ms to four ranges of activities around the mean firing rates (+/-0.5 SD) and were converted to four values. After comparison of the values of two chosen neuron units, direction and speed of rotation were decided. Rats were trained to complete one-dimensional control task to obtain water reward. The results indicated the percentage of stop event increased alone with more training. Different brain activity significantly influenced total water-drinking duration and non-water-drinking duration. Events generated from neuronal activity differed according to variant experimental sessions. Correlation between two signal units impacted controlling performance. Overall, the results of this study suggest that rats were able to manipulate the 1-D BCI system by differentially modulating PFC single neuron activities according to different circumstances.
Adult ; Animals ; Brain ; Brain-Computer Interfaces ; Fires ; Humans ; Male ; Neurons ; Prefrontal Cortex ; Rats ; Rats, Sprague-Dawley ; Reward ; Water

Dysfunction of the nucleus accumbens (NAcb) is implicated in the development of anhedonia, a core symptom of major depressive disorder. In order to define the neural basis of depression-like behaviors induced by experience of neonatal maternal separation (MS), both basal and stress-induced neuronal activations in the NAcb of adolescent rats with MS experience were examined parallel with palatable food intake. Rat pups were separated from dam daily for 180 min during the first two weeks of age (MS), and non-handled control (NH) pups were left undisturbed. After weaning on postnatal day (PND) 22, a half of NH or MS pups were subjected to 1 h of restraint stress every even day during PND 28~40 (NH/R or MS/R), and then had free choices of chow and chocolate cookie for 1 h immediately after returned to home cage. The rest half of NH and MS pups (NH/C or MS/C) received free choices of chow and cookie in the same time schedule with stress group, just omitting restraint stress. Cookie intake was significantly decreased in MS/C, whereas c-Fos expression in the NAcb and plasma corticosterone increased, compared to NH/C. Restraint stress suppressed cookie intake and increased the NAcb c-Fos expression in NH/R, but not in MS/R. The plasma corticosterone of NH/R, but not of MS/R, increased following repeated restraint stress. These results suggest that the increased neuronal activation in the NAcb of MS/C may be implicated in the development of anhedonia by MS experience, perhaps, in relation with a blunted responsivity of the hypothalamic-pituitary- adrenal axis to stress.
Adolescent ; Anhedonia ; Animals ; Appointments and Schedules ; Cacao ; Corticosterone ; Depression ; Depressive Disorder, Major ; Eating ; Humans ; Neurons ; Nucleus Accumbens ; Plasma ; Rats ; Weaning ; Axis, Cervical Vertebra

The behavior of most animals is extremely complex. Despite accumulating knowledge about the mechanisms of neurons and nervous systems, which regulate these complex behaviors, we have little understanding about how these mechanisms function. In the present study, we analyzed the exploratory behavior of mice repeatedly exposed to a novel context and tracked the changes in the fluctuation patterns of the accumulated level of body movement suppression (BMS). As a result, we found that the fluctuation in BMS can be divided into two phases, which show a pattern of progressive transition from the initial state to the context-dependent and stable equilibrium state. In the former, transition phase, the level of BMS was easily affected by the number of exposures and mental status of mice. However, in the latter, equilibrium phase, the level of BMS was only dependent on the environmental stimuli involved in the context. On the basis of the results, we suggests here a model that explains the determination of complex behavior observed in higher animals by means of the probability of behavioral expression.
Animals ; Exploratory Behavior ; Mice ; Nervous System ; Neurons ; Track and Field

Freezing behavior is a widely used parameter that represents the level of fear. A number of studies on emotional learning have used this behavior for quantification of fear that results from a cue or a context. Even though the expression of freezing behavior is based on the dynamic interaction of mice with the environment, the effect of environmental stimuli on freezing behavior has not been studied extensively because of its minority compared to the effect of conditioning-stimuli. In this study, we found that the auditory environment of a context affects the freezing behavior of a mouse in it. This effect was not observed when the mouse was exposed to the context for the first time. However, during the second exposure, the level of freezing behavior increased significantly in an intensity-dependent manner, while the type, pitch, and rhythm of additional sounds involved in the context did not induce notable effects. This intensity-dependent effect was unrelated to the level of fear and anxiety, reflecting another aspect of the freezing behavior as a parameter for recognizing the pattern of normal behaviors.
Animals ; Anxiety ; Cues ; Freezing ; Learning ; Mice

mTOR is a serine/threonine kinase composed of multiple protein components. Intracellular signaling of mTOR complexes is involved in many of physiological functions including cell survival, proliferation and differentiation through the regulation of protein synthesis in multiple cell types. During brain development, mTOR-mediated signaling pathway plays a crucial role in the process of neuronal and glial differentiation and the maintenance of the stemness of neural stem cells. The abnormalities in the activity of mTOR and its downstream signaling molecules in neural stem cells result in severe defects of brain developmental processes causing a significant number of brain disorders, such as pediatric brain tumors, autism, seizure, learning disability and mental retardation. Understanding the implication of mTOR activity in neural stem cells would be able to provide an important clue in the development of future brain developmental disorder therapies.
Autistic Disorder ; Brain Diseases ; Brain Neoplasms ; Brain* ; Cell Survival ; Intellectual Disability ; Learning Disorders ; Neural Stem Cells ; Neurogenesis ; Neurons ; Phosphotransferases ; Seizures

To date, numerous case-control studies have shown the complexity of the pathogenesis of Parkinson's disease (PD). In terms of genetic factors, several susceptibility genes are known to contribute to the development of PD, including alpha-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2), and glucocerebrosidase (GBA). In addition, numerous recent epidemiological studies have shown that several environmental factors are either risk factors for PD or protective factors against PD. Risk factors identified include herbicides and pesticides (e.g., paraquat, rotenone, and maneb), metals (e.g., manganese and lead), head trauma, and well water. In contrast, smoking and coffee/caffeine consumption are known to be protective against PD. A recent finding in this field is that environmental-genetic interactions contribute more to the pathogenesis of PD than do genetic factors or environmental factors alone. In this review, I will discuss how these interactions promote the development of PD.
alpha-Synuclein ; Case-Control Studies ; Craniocerebral Trauma ; Glucosylceramidase ; Herbicides ; Manganese ; Metals ; Paraquat ; Parkinson Disease ; Pesticides ; Phosphotransferases ; Risk Factors ; Rotenone ; Smoke ; Smoking ; Water wells