Basic and Clinical Neuroscience
Volume:11 Issue: 1, Jan-Feb 2020

Efficient gait control using Functional Electrical Stimulation (FES) is an open research problem. In this research, a new intermittent controller has been designed to control the human shank movement dynamics during gait.

In this approach, first, the three-dimensional phase space was constructed using the human shank movement data recorded from the healthy subjects. Then, three iterated sine-circle maps were extracted in the mentioned phase space. The three identified one-dimensional maps contained the essential information about the shank movement dynamics during a gait cycle. Next, an intermittent fuzzy controller was designed to control the shank angle. According to the adopted intermittent control strategy, the fuzzy controller is activated whenever the shank angle is far enough from the specific. The specific points are described using the identified iterated maps in the constructed phase space. In this manner, the designed controller is activated during a short-time fraction of the gait cycle time.

The designed intermittent controller was evaluated through some simulation studies on a two-joint musculoskeletal model. The obtained results suggested that the pattern of the obtained hip and knee joint trajectories, the outputs of the musculoskeletal model, were acceptably similar to the joints’ trajectories pattern of healthy subjects. 

The intriguing similarity was observed between the dynamics of the recorded human data and those of the controlled musculoskeletal model. It supports the acceptable performance of the proposed control strategy.

Glycogen Synthase Kinase-3β (GSK-3β) participates in several signaling pathways and plays a crucial role in neurodegenerative diseases, inflammation, and neuropathic pain. The ratio of phosphorylated GSK-3β over total GSK-3β (p-GSK-3β/t-GSK-3β) is reduced following nerve injury. Apoptosis is a hallmark of many neuronal dysfunctions in the context of neuropathic pain. Thus, this study aimed to evaluate the contribution of p-GSK-3β/t-GSK-3β ratio in spinal dorsal horn apoptosis following peripheral nerve injury. 

In this study, adult male Wistar rats (220-250 g) underwent Spinal Nerve Ligation (SNL) surgery. Mechanical allodynia and thermal hyperalgesia were assessed before the surgery (day 0); then, every other day up to day 8. GSK-3β selective inhibitor, AR-014418 [0.3 mg/kg, Intraperitoneal (IP)] was administrated 1 h prior to SNL on day 0, then daily up to the day 8. The GSK-3β activity and apoptosis in the lumbar section (L4, L5, or L6) of the study rat’s spinal cord were assessed by immunohistochemical and Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) staining, respectively on day 8 post-SNL. 

Following the SNL, the mechanical allodynia and thermal hyperalgesia increased on day 2 up to day 8 post-SNL. The ratio of p-GSK-3β/t-GSK-3β decreased, and the number of apoptotic cells increased in the spinal dorsal horn on day 8. However, AR-A014418 administration could increase the p-GSK-3β/t-GSK-3β ratio and decreased apoptosis in the SNL rats. In addition, AR-A014418 decreased the mechanical allodynia from day 4 up to day 8; however, it did not affect thermal hyperalgesia. 

The study findings suggested that increasing the p-GSK-3β/t-GSK-3β ratio might be a helpful strategy for reducing the apoptotic cells and subsequent neuropathic pain during peripheral nerve injury.

The proteoglycans of the extracellular matrix increases in the glial scar during spinal cord injury and significantly affects the inhibition of axonal regeneration. 

The results of injury therapies are limited due to the lack of identifying a timely therapeutic intervention. The present study aimed to investigate the glial scar Chondroitin Sulfate (CS) and Dermatan Sulfate (DS) levels at different post-injury times to determine the appropriate time for therapeutic intervention. 

By this experimental study, 72 Wistar rats were randomly divided into 12 groups, as follows: control, sham, injured animals at 1, 2, 4, and 8 days, as well as 2, 4, 8, 12, 16, and 20 weeks post-injury. The animals in the injured groups were contused in the T10 segment of the spinal cord. The motor function of animals was assessed using the Basso, Beattie, and Bresnahan (BBB) test. Besides, the histological assessment was performed using Luxol Fast Blue and Bielshovisky Staining. The CS and DS levels of lesions were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. 

The motor function assessment indicated a relative recovery over time. Histological results confirmed some regeneration in the injury site at 20 weeks post-injury. The ELISA results demonstrated a much higher level of DS than that of CS in the glial scar. Considering high levels of DS, compared to CS in the glial scar and its reduction from second weeks after SCI onwards, the second week after SCI seems to be the best time for therapeutic interventions in terms of scar permeability.

Kainic Acid (KA) is an ionotropic glutamate receptor agonist. KA can induce neuronal overactivity and excitotoxicity. Rosmarinic Acid (RA) is a natural polyphenolic compound with antioxidant, anti-apoptotic, anti-neurodegenerative, and anti-inflammatory properties. This study aimed to assess the effect of RA on apoptosis, nNOS-positive neurons number, as well as Mitogen-Activated Protein Kinase (MAPK) and Cyclooxygenase-2 (COX-2) immunoreactivity, following intrahippocampal Kainic acid injection in rats. 

The study rats were randomly assigned to three groups of sham, KA (KA was injected into the right side of the hippocampus) and KA+RA (a dose of 10 mg/kg/day through a gavage needle for one week before KA injection). Then, histopathological changes, including apoptosis [Terminal Deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay], nNOS-positive neurons number, as well as COX-2 and MAPK immunoreactivity were evaluated in the hippocampus. 

In the RA pretreated group, nNOS-positive neurons and TUNEL- positive cells were significantly reduced compared to the KA group (P<0.05). COX-2and MAPK immunoreactivity demonstrated no significant changes compared to the KA group. They indicated a significant higher reactivity for COX-2 (P<0.01) and MAPK (P<0.005) versus the sham group. 

RA had neuroprotective effects, compared to KA, through reduced apoptosis and nNOS-positive neurons, but not MAPK and COX-2.

Microglia, small glial cells, i.e. mesodermal in origin and found in the brain and spinal cord, play a key role in the maintenance of neurons and immune defense. Haloperidol, an antipsychotic drug, is used to treat numerous neurological and neurodegenerative disorders. Its mechanism is not understood; however, haloperidol may result in Wnt signaling pathway activation. This study aimed to activate the Wnt signaling pathway using haloperidol and determining the effect of GSK3 inhibition on the expression of TGFB, NT-3, and BDNF genes in cultured rat microglia. 

Microglia isolation was conducted, and the immunohistochemistry technique was performed to confirm microglia purity. The RNA extraction was followed by cDNA synthesis. Real-time RT-PCR was used to evaluate any significant changes in the expression level of these genes. 

The three gene expressions in microglia were proportional to the different concentrations of the drug. More concentration of drugs resulted in higher levels of expression of these genes. Besides, the haloperidol did not affect the expression of the beta-actin gene as the reference gene. 

The obtained results supported the beneficial use of haloperidol in targeted microglia therapy. This study can be a breakthrough in neurology research.

Consuming antidepressant medications induce several problems leading to the need for alternative agents for emotional disturbances. Antidepressant medications increase the seizure risk; thus, alternative treatments, like Antiepileptic Drugs (AED), might be useful for patients with epilepsy comorbid with a psychiatric disorder. The present study evaluated the behavioral effects of sodium valproate, a none effective dose in seizure treatment [100 mg/kg; Intraperitoneal (IP)] along with the application of Low-Frequency Stimulations (LFS) during CA1 hippocampal kindling.

In total, 42 male rats were randomly divided into 6 groups, including control group with intact animals handled daily (I); sham group which was subjected to the surgical process, but received no real stimulation (II); saline-kindled Kindled group (S.kindled) which were stimulated daily with the following protocol: 3 strain of 50Hz monophasic pulses of 1ms duration applied 12 times a day with the threshold intensity at intervals of 10 minutes where saline was administrated 15 min before kindling stimulations (III); saline-kindled-LFS group (K4LFS) in which saline was injected 15 min before kindling stimulations and LFS was applied daily after the termination of kindling stimulation (IV ); drug-kindle group (Drug100.kindled) that underwent rapid kindling procedure daily where sodium valproate (100 mg/kg) was administrated 15 min before kindling stimulations(V), and drug-kindled-LFS (Drug100.kindled.4LFS) group in which drug and LFS were administrated respectively before and after kindling stimulations (VI). The behavioral tests were assessed using elevated plus maze, open field, and forced swim tests. 

The combination of sodium valproate (100 mg/kg) and LFS significantly decreased cumulative seizure severity compared with the kindle group. Thus, it provided a strong seizure suppressing effect. Additionally, sodium valproate and LFS increased the percentage of Open Arms (OAs) entries and the OAs exploration; they also decreased jumping from elevated plus maze test and rearing in open field test. Furthermore, there was no significant change in the OAs entries and OAs exploration percentages, jumping from apparatus, and rearing in open field in Drug100. Kindled, K4LFS, and Drug100.kindled.LFS groups, compared with the sham group. There was no significant difference in the latency to first immobility and the duration of immobility in K4LFS groups compared with the S. kindled group. In the drug-kindled group, the latency to first immobility significantly increased, and the duration of immobility decreased, compared with the S. kindled group. Besides, the latency to first immobility significantly increased, and the duration of immobility decreased in drug-kindled-LFS, compared to S. kindled group; however, the latency to first immobility was not significantly changed, compared to drug-kindled groups.

Sodium valproate and LFS can modulate the function of the brain regions involved in emotional processing in epilepsy, as well as anxiety- and depressive-like behaviors. Such a combination could also decrease emotional disturbances induced by the kindling process.

According to evidence, Early-Life Stress (ELS), mood disorders, and medical comorbidities, i.e.  Irritable Bowel Syndrome (IBS), are correlated; however, the direct contribution of ELS to IBS manifestations is less understood. The current study aimed at evaluating the effect of voluntary exercise on the mitochondrial dysfunction of the bowel fibroblasts, following the confirmation of anxiety behavior. 

In this study, Postnatal Day (PND) rats underwent Maternal Separation (MS), as a valid animal model of the brain-gut axis dysfunction, in the days 2-14; three hours daily. On day 21, the study animals were divided into 4 groups, as follows: control, Running Wheel (RW) exercise, MS, and MS+RW groups. The study groups were housed in separate cages (4 rats per cage) until the onset of intervention. On day 60, the elevated plus-maze was used to assess anxiety-like behaviors; the level of oxidative stress biomarkers, i.e.  Reactive Oxygen Species (ROS), Glutathione (GSH) , as well as Adenosine Triphosphate (ATP) was measured to determine the gut mitochondrial function. 

Findings revealed that ELS affected the gut energy metabolism in the studied rats; the negative effects of MS on anxiety and the gut mitochondrial dysfunction decreased via RW exercise during adolescence. 

Overall, anxiety behaviors and ROS production, leading to increased GSH and ATP levels, improved after RW exercise; this significantly impacts the function of colon secretory mitochondria. According to the positive effects of RW exercise on mitochondrial dysfunction in an ELS animal model, a potential relationship was found between the brain and gut in the study rats.

Identifying the potential firing patterns following different brain regions under normal and abnormal conditions increases our understanding of events at the level of neural interactions in the brain. Furthermore, it is important to be capable of modeling the potential neural activities to build precise artificial neural networks. The Izhikevich model is one of the simplest biologically-plausible models, i.e. capable of capturing most recognized firing patterns of neurons. This property makes the model efficient in simulating the large-scale networks of neurons. Improving the Izhikevich model for adapting with the neuronal activity of rat brain with great accuracy would make the model effective for future neural network implementations.

Data sampling from two brain regions, the HIP and BLA, was performed by the extracellular recordings of male Wistar rats, and spike sorting was conducted by Plexon offline sorter. Further analyses were performed through NeuroExplorer and MATLAB. To optimize the Izhikevich model parameters, a genetic algorithm was used. In this algorithm, optimization tools, like crossover and mutation, provide the basis for generating model parameters populations. The process of comparison in each iteration leads to the survival of better populations until achieving the optimum solution.

In the present study, the possible firing patterns of the real single neurons of the HIP and BLA were identified. Additionally, an improved Izhikevich model was achieved. Accordingly, the real neuronal spiking pattern of these regions’ neurons and the corresponding cases of the Izhikevich neuron spiking pattern were adjusted with great accuracy. 

This study was conducted to elevate our knowledge of neural interactions in different structures of the brain and accelerate the quality of future large-scale neural networks simulations, as well as reducing the modeling complexity. This aim was achievable by performing the improved Izhikevich model, and inserting only the plausible firing patterns and eliminating unrealistic ones.

The present study aimed to investigate the antidepressant effect of Verbena (V.) officinalis L. aqueous extract in adult female rats. 

The present study evaluated the antidepressant effect of V. officinalis L. aqueous (V AE) extract in female rats using the Forced-Swimming Test (FST), Light-Dark Box (LDB) test, and Open Field Test (OFT). The level of glycemia and histological analysis were also studied. The VAE [200 mg/kg Parenterally (PO)] was administered orally for 7 successive days in the separate groups of rats. 

The oral administration of V. officinalis L. aqueous extract significantly decreased (P< 0.01) the immobility time in the FST, increased the time spent in the light area (LDB), and the number of entry into the central squares (OFT). Thus, the extract at a dose of 200 mg/kg significantly decreased the glycemia level (P<0.05) and suggested no harmful effect on brain histology.

Verbena officinalis L. aqueous extract at a dose of 200 mg/kg could have an anti-depressant effect in adult rats.

This study aimed to compare the effectiveness of computer-based, manual-based, and combined cognitive rehabilitation to improve cognitive functions among patients with Relapsing-Remitting Multiple Sclerosis (RRMS).

This was a quasi-experimental study with a pre-test-post-test, and a 2-month follow-up, as well as a control group design. Sixty female patients with RRMS were selected by convenience sampling technique. Then they were randomly assigned into three experimental groups (computer-based, manual-based, and combined cognitive rehabilitation, each group including 12 patients), a placebo group (12 patients), and a control group (12 patients). The interventions were conducted in 21 sessions for the experimental groups for 5 months. The placebo group received physical rehabilitation intervention, and the control group received no intervention. The study participants were assessed by Psychiatric-Neurological Profile, Mini-Mental State Examination, Kurtzke Expanded Disability Status Scale, Stroop Color and Word Test, Wisconsin Card Sorting Test, and Paced Auditory Serial Addition Test. The obtained data were analyzed by repeated-measures multivariate analysis of variance in SPSS.

The effect of group factor was not significant (η2=0.129), but the effect of time (η2=0.884) and interaction effect of time and group (η2=0.295) were statistically significant (P<0.05). There was no significant difference between the effects of all three rehabilitation interventions (P>0.05). In the post-test totally and in Follow-up partially, all comparisons among three experimental groups with control and placebo groups were statistically significant (P<0.05). 

Cognitive rehabilitation was effective in improving cognitive functions in patients with RRMS. Thus, these interventions are recommended for application, along with other treatment protocols to treat RRMS in clinical settings.

Obsessive-Compulsive Disorder (OCD) belongs to the categories of psychiatric disorders with the potential to turn into a chronic condition without receiving the necessary treatments. The main feature of OCD is the frequent or intense obsession and compulsion that might induce great pain and suffering in patients. Moreover, as one of the most prevalent abnormalities, depression usually follows OCD. The present study aimed to compare the effects of Exposure and Response Prevention (ERP) and Transcranial Direct Current Stimulation (tDCS) treatments adjunct to pharmacotherapy on decreasing the severity of obsession-depression symptoms and improving the quality of life in OCD patients.

This was a quasi-experimental study with a pre-test, post-test design and a follow-up stage. The statistical population comprised all the patients diagnosed with OCD in Zanjan Province, Iran. Besides, 26 OCD patients referring to Shahid Beheshti Medical Center in Zanjan were selected using a purposive sampling method. Then, they were randomly assigned to two treatment groups. The study subjects completed the Yale Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Depression Inventory-II (BDI 2), and the Quality of Life Questionnaire at the pre-treatment, post-treatment, and follow-up stages (1 month and 2 months after the treatment). Analysis of Covariance (ANCOVA) and Reliable Change Index (RCI) methods were used to measure statistical and clinical significances, respectively. The collected data were analyzed using SPSS.

The obtained data suggested no significant difference between the ERP and tDCS groups concerning the symptoms of OCD and depression at the post-test stage (P>0.05). Conversely, in terms of life quality, there was a significant difference between the ERP and tDCS groups at the post-test phase (P<0.05).

Although the present findings revealed no statistically significant difference between the ERP and tDCS groups (except for the quality of life variable), the pharmacotherapy-ERP combination proved to be more effective than pharmaco therapy- tDCS in treating OCD patients.

The neural response is a noisy random process. The neural response to a sensory stimulus is completely equivalent to a list of spike times in the spike train. In previous studies, decreased neuronal response variability was observed in the cortex’s various areas during motor preparatory in reaching tasks. The reasons for the reduction in Neural Variability (NV) are unclear. It could be influenced by an increased firing rate, or it could result from the intrinsic characteristic of cells during the Reaction Time (RT).

A neural response function with an underlying deterministic instantaneous firing rate signal and a random Poisson process spike generator was simulated in this research. Neural stimulation could help us understand the relationships between the complex data structures of cortical activities and their stability in detail during motor intention in arm-reaching tasks. 

Our measurements indicated a similar pattern of results to the cortex, a sharp reduction of the normalized variance of simulated spike trains across all trials. We also observed a reverse relationship between activity and normalized variance.

The present study findings could be applied to neural engineering and brain-machine interfaces for controlling external devices, like the movement of a robot arm.