Xiaoxiang Zheng

The Effects of Voluntary, Involuntary, and Forced Exercises on Brain-Derived Neurotrophic Factor and Motor Function Recovery: A Rat Brain Ischemia Model

Background Stroke rehabilitation with different exercise paradigms has been investigated, but which one is more effective in facilitating motor recovery and up-regulating brain neurotrophic factor (BDNF) after brain ischemia would be interesting to clinicians and patients. Voluntary exercise, forced exercise, and involuntary muscle movement caused by functional electrical stimulation (FES) have been individually demonstrated effective as stroke rehabilitation intervention. The aim of this study was to investigate the effects of these three common interventions on brain BDNF changes and motor recovery levels using a rat ischemic stroke model. Methodology/Principal Findings One hundred and seventeen Sprague-Dawley rats were randomly distributed into four groups: Control (Con), Voluntary exercise of wheel running (V-Ex), Forced exercise of treadmill running (F-Ex), and Involuntary exercise of FES (I-Ex) with implanted electrodes placed in two hind limb muscles on the affected side to mimic gait-like walking pattern during stimulation. Ischemic stroke was induced in all rats with the middle cerebral artery occlusion/reperfusion model and fifty-seven rats had motor deficits after stroke. Twenty-four hours after reperfusion, rats were arranged to their intervention programs. De Rycks behavioral test was conducted daily during the 7-day intervention as an evaluation tool of motor recovery. Serum corticosterone concentration and BDNF levels in the hippocampus, striatum, and cortex were measured after the rats were sacrificed. V-Ex had significantly better motor recovery in the behavioral test. V-Ex also had significantly higher hippocampal BDNF concentration than F-Ex and Con. F-Ex had significantly higher serum corticosterone level than other groups. Conclusion/Significance Voluntary exercise is the most effective intervention in upregulating the hippocampal BDNF level, and facilitating motor recovery. Rats that exercised voluntarily also showed less corticosterone stress response than other groups. The results also suggested that the forced exercise group was the least preferred intervention with high stress, low brain BDNF levels and less motor recovery.

An in vitro study of vascular endothelial toxicity of CdTe quantum dots

Quantum dots (QDs), as novel bioimaging and drug delivery agents, are generally introduced into vascular system by injection, and thus directly exposed to vascular endothelial cells (ECs). However, the adverse effects of QDs on ECs are poorly understood. In this study, employing human umbilical vein ECs (HUVECs), we investigated the potential vascular endothelial toxicity of mercaptosuccinic acid (MSA)-capped CdTe QDs in vitro. In the experiment, water-soluble and pH stable CdTe QDs were synthesized; and the cell viability assays showed that CdTe QDs (0.1-100μg/mL) dose-dependently decreased the cell viability of HUVECs, indicating CdTe QDs induced significant endothelial toxicity. The flow cytometric and immunofluorescence results revealed that 10μg/mL CdTe QDs elicited significant oxidative stress, mitochondrial network fragmentation as well as disruption of mitochondrial membrane potential (Δψ(m)); whereas ROS scavenger could protect HUVECs from QDs-induced mitochondrial dysfunction. Moreover, upon 24h exposure to 10μg/mL CdTe QDs, the apoptotic HUVECs dramatically increased by 402.01%, accompanied with alternative expression of apoptosis proteins, which were upregulation of Bax, downregulation of Bcl-2, release of mitochondrial cytochrome c and cleavage of caspase-9/caspase-3. These results suggested that CdTe QDs could not only impair mitochondria but also exert endothelial toxicity through activation of mitochondrial death pathway and induction of endothelial apoptosis. Our results provide strong evidences of the direct toxic effects of QDs on human vascular ECs, and reveal that exposure to QDs is a significant risk for the development of cardiovascular diseases. These results also provide helpful guidance on the future safe use and manipulation of QDs to make them more suitable tools in nanomedicine.

Role for Nitric Oxide in Permeability of Hippocampal Neuronal Hemichannels During Oxygen Glucose Deprivation

Increased hemichannel opening induced by oxygen glucose deprivation (OGD) was reported in the hippocampal pyramidal neuron. It was suggested that the pannexin1 hemichannel opening could mediate ionic flux dysregulation, anoxic depolarization, and energy‐depleting efflux of glucose and ATP for ischemic neurons. However, the regulatory mechanisms of pannexin1 hemichannel opening have been poorly understood. Here we showed that excessive generation of nitric oxide (NO) during ischemia could induce the calcein leakage from neurons, which was markedly reduced by NO synthase inhibitor. The calcein leakage from neurons during OGD was also attenuated by the application of N‐ethylmaleimide (NEM), an SH‐alkylating agent, and dithiothreitol (DTT), a reducer of oxidized sulfhydryl groups. However, the soluble guanylyl cyclase (sGC) inhibitor had a minor effect on the calcein leakage during OGD. Furthermore, the elevated intracellular but not extracellular levels of glutathione could also inhibit the calcein leakage during OGD. Similar results were observed in metabolic inhibition (MI), which is another ischemic‐like condition. Finally, immunocytochemical and immunoblotting analysis revealed that, after 1 hr of OGD stimulation, the distribution and expression of pannexin1 showed no significant difference compared with control. However, the pannexin1 mRNA expression was elevated after 1 hr of OGD and a sustained increase was maintained during reperfusion. These results implied that the reactive oxygen species (ROS), especially NO, might be involved in the enhanced pannexin1 hemichannel opening and that the S‐nitrosylation but not the NO/cGMP pathway played a more important role in this event.

Salidroside stimulated glucose uptake in skeletal muscle cells by activating AMP-activated protein kinase.

In the present study, we reported the metabolic effects of salidroside, one of the active components of Rhodiola Rosea, on skeletal muscle cells. Salidroside dose-dependently stimulated glucose uptake in differentiated L6 rat myoblast cells. Inhibitor of AMP-activated protein kinase (AMPK) by pretreating the cells with compound C potently reduced salidroside-stimulated glucose uptake, while inhibition of phosphatidylinositol 3-kinase (PI3K) by wortmannin exhibited no significant inhibitory effect on salidroside-mediated glucose transport activation. Western blotting analyses revealed that salidroside increased the phosphorylation level of AMPK and acetyl-CoA carboxylase (ACC). In addition, salidroside enhanced insulin-mediated Akt activation and glucose uptake, and such enhancement can be specifically inhibited by compound C. In summary, AMPK activation was involved in the effects of salidroside on glucose transport activation and insulin sensitivity. Salidroside can be further developed as potential compound for the anti-diabetic therapy.

Autophagy plays a protective role in free cholesterol overload-induced death of smooth muscle cells

Smooth muscle cells (SMC) make up most of the vascular system. In advanced atherosclerotic plaques, dying SMCs undergo a complex death mode. In the present study, we examined the activation of autophagy in SMCs overloaded with excess free cholesterol (FC) and investigated the possible role which autophagy plays during the FC-induced cell death. After incubation with excess FC, a robust expression of autophagic vacuoles (AV) was detected using both fluorescence microscopy and transmission electron microscopy (TEM). The results revealed that FC induced a time-dependent upregulation of microtubule-associated protein-1 light chain 3-II (LC3-II). Inhibition of autophagy by 3-methyladenine (3-MA) enhanced both cell apoptosis and necrosis, while on the contrary, rapamycin inhibited cell death following cholesterol application. Furthermore, the impact of the colocalization of fragmented mitochondria with AVs was observed after cholesterol treatment. Our results also revealed that the modulation of autophagy directly influenced the cellular organellar stress. In conclusion, our findings demonstrated that excess FC induced the activation of autophagy in SMCs as a cellular defense mechanism, possibly through the degradation of dysfunctional organelles such as mitochondria and endoplasmic reticulum.

A portable telemetry system for brain stimulation and neuronal activity recording in freely behaving small animals

A portable multi-channel telemetry system which can be used for brain stimulation and neuronal activity recording in freely behaving small animals is described here. This system consists of three major components of headstage, backpack and portable Personal Digital Assistant (PDA). The headstage contains high precision instrument amplifiers with high input impedance. The backpack is comprised of two parts: (1) a main board (size: 36 mm x 22 mm x 3.5 mm and weight: 40 g with batteries, 20 g without), with current/voltage stimulator and special circuit suitable for neuronal activity recording and (2) and a bluetooth transceiver, with a high data transmission rate up to 70 kb/s, suitable for downloading stimulation commands and uploading acquired data. We recorded neuronal activities of the primary motor area of a freely behaving rat with 12-bit resolution at 12 k samples/s. The recorded data and analysis results showed that the system was successful by comparing with the commercial equipment Cerebus 128-Channel Data Acquisition System (Cyberkinetics Inc.). Using the PDA, we can control stimulation and recording. It provides a flexible method to do some research work in the circumstances where other approaches would be difficult or impossible.

Protective effects of galantamine against Aβ-induced PC12 cell apoptosis by preventing mitochondrial dysfunction and endoplasmic reticulum stress

Amyloid beta (Abeta) is considered to be responsible for the pathogenesis of Alzheimers disease (AD). Mitochondrial and ER apoptotic pathways are considered to be involved in this process. Galantamine is an acetylcholinesterase (AChE) inhibitor widely used for patients with AD. In this study, we investigated the neuroprotective effects of galantamine on Abeta(25-35)-induced apoptosis in PC12 cells and the underlying mechanisms. Exposure of PC12 cells to 20 microM Abeta(25-35) caused significant cell viability loss and apoptosis, Abeta aggregation, mitochondrial and ER morphological changes, as well as mitochondrial membrane potential dissipation, reactive oxygen species (ROS) production, intracellular calcium elevation, and cytochrome c release from mitochondria. Pretreatment with 10 microM galantamine for 24 h prior to Abeta(25-35) exposure significantly reduced Abeta(25-35)-induced apoptosis not only by preventing Abeta aggregation, mitochondrial and ER morphological changes, mitochondrial membrane potential dissipation, ROS production, intracellular calcium elevation, and cytochrome c release, but also via reversing Bcl-2/Bax ratio and suppressing the activity of GADD153, Grp78/94, caspase-9, caspase-12, and caspase-3. All these data indicate that galantamine protects PC12 cells against Abeta(25-35)-induced apoptosis by preventing mitochondrial dysfunction and endoplasmic reticulum (ER) stress.

Tungsten bronze type dielectrics in SrO-Sm2O3-TiO2-Nb2O5 system and their dielectric anomaly

The dielectric behavior and the features of the diffused phase transition of the SrpSm6−pTi8−pNb2+pO30(p=4,5) ceramics were investigated together with their structure. Both Sr5SmTi3Nb7O30 and Sr4Sm2Ti4Nb6O30 had tungsten bronze structure and weak ferroelectric nature. Though Sr5SmTi3Nb7O30 showed the diffused ferroelectrics phase transition, it was concluded that the transition was mainly the displacive ferroelectric phase transition. In Sr4Sm2Ti4Nb6O30, the Sr2+ ions and Sm3+ ions did not form an order structure and it showed a typical displacive ferroelectric phase transition. The dielectric anomaly was attributed to the different BO6 octahedral distortion.

A hybrid brain-computer interface control strategy in a virtual environment

This paper presents a hybrid brain-computer interface (BCI) control strategy, the goal of which is to expand control functions of a conventional motor imagery or a P300 potential based BCI in a virtual environment. The hybrid control strategy utilizes P300 potential to control virtual devices and motor imagery related sensorimotor rhythms to navigate in the virtual world. The two electroencephalography (EEG) patterns serve as source signals for different control functions in their corresponding system states, and state switch is achieved in a sequential manner. In the current system, imagination of left/right hand movement was translated into turning left/right in the virtual apartment continuously, while P300 potentials were mapped to discrete virtual device control commands using a five-oddball paradigm. The combination of motor imagery and P300 patterns in one BCI system for virtual environment control was tested and the results were compared with those of a single motor imagery or P300-based BCI. Subjects obtained similar performances in the hybrid and single control tasks, which indicates the hybrid control strategy works well in the virtual environment.

Protective Effects of Echinacoside, One of the Phenylethanoid Glycosides, on H2O2-Induced Cytotoxicity in PC12 Cells

We have investigated the protective effects of echinacoside (ECH), one of the phenylethanoid glycosides, on H(2)O(2)-induced cytotoxicity in the rat pheochromocytoma cell line (PC12 cells). Our data show that application of ECH to H(2)O(2)-injured PC12 cells (HIPCs) increased cell viability and decreased the apoptotic ratio. Flow cytometry (FCM) and laser scanning confocal microscopy (LSCM) analysis suggested that ECH exerted its inhibitory effects on the formation of reactive oxygen species (ROS) and the accumulation of intracellular free Ca(2+) ([Ca(2+)]i). In addition, ECH elevated the mitochondrial membrane potential (MMP) in HIPCs. Furthermore, Western blot analysis revealed that ECH prevented an H(2)O(2)-induced increase of the Bax/Bcl-2 ratio by down-regulating Bax protein expression and upregulating Bcl-2 protein expression. In summary, ECH showed significant neuroprotective effects on HIPCs through the mitochondrial apoptotic pathway, and could be a potential candidate for intervention in neurodegenerative diseases such as Alzheimers and Parkinsons disease.