Basic and Clinical Neuroscience
Volume:12 Issue: 2, Mar-Apr 2021

about 20% to 30% of patients with epilepsy are diagnosed with drug-resistant epilepsy and one third of these are candidates for epilepsy surgery. Surgical resection of the epileptogenic tissue is a well-established method for treating patients with intractable focal epilepsy. Determining language laterality and locality is an important part of a comprehensive epilepsy program before surgery. Functional Magnetic Resonance Imaging (fMRI) has been increasingly employed as a non-invasive alternative method for the Wada test and cortical stimulation. Sensitive and accurate language tasks are essential for any reliable fMRI mapping. 

The present study reviews the methods of presurgical fMRI language mapping and their dedicated fMRI tasks, specifically for patients with epilepsy.

Different language tasks including verbal fluency are used in fMRI to determine language laterality and locality in different languages such as Persian. there are some considerations including the language materials and technical protocols for task design that all presurgical teams should take into consideration.

Accurate presurgical language mapping is very important to preserve patients language after surgery. This review was the first part of a project for designing standard tasks in Persian to help precise presurgical evaluation and in Iranian PWFIE.

Brain injury induces an almost immediate response from glial cells, especially astrocytes. Activation of astrocytes leads to the production of inflammatory cytokines and reactive oxygen species that may result in secondary neuronal damage. Melatonin is an anti-inflammatory and antioxidant agent, and it has been reported to exert neuroprotection through the prevention of neuronal death in several models of central nervous system injury. This study aimed to investigate the effect of melatonin on astrocyte activation induced by Traumatic Brain Injury (TBI) in rat hippocampus and dentate gyrus. 

Animals were randomly divided into 5 groups; Sham group, TBI group, vehicle group, and melatonin‐treated TBI groups (TBI+Mel5, TBI+Mel20). Immunohistochemical method (GFAP marker) and TUNEL assay were used to evaluate astrocyte reactivity and neuronal death, respectively. 

The results demonstrated that the astrocyte number was reduced significantly in melatonin‐treated groups compared to the vehicle group. Additionally, based on TUNEL results, melatonin administration noticeably reduced the number of apoptotic neurons in the rat hippocampus and dentate gyrus. 

In general, our findings suggest that melatonin treatment after brain injury reduces astrocyte reactivity as well as neuronal cell apoptosis in rat hippocampus and dentate gyrus.

Obsessive-Compulsive Disorder (OCD) is one of the complex neuropsychiatric conditions. This disorder disables individuals in many different aspects of their personal and social life. Interactome analysis may provide a better understanding of this disorder’s molecular origin and its underlying mechanisms.

In this study, the OCD-associated genes were extracted from the literature. The criterion for gene selection was to choose genes with at least one significant report. Furthermore, by applying Cytoscape and its plugins, protein-protein interaction network, and gene ontology of the 31 candidate genes related to OCD from genetic association studies is examined. The cross-validation method was used for network centrality assessment.

A scale-free network, including 1940 nodes and 3269 edges for 31 genes, was constructed. According to the network centrality evaluation, ESR1, TNFα, DRD2, DRD4, HTR1B, HTR2A, and CDH2 showed the highest values and can be considered hub-bottlenecks elements. It is also confirmed by the number of 123 cross-validation tests that the frequency of these essential genes remains unaltered against the initial seed genes’ changes with the accuracy of 0.962. Besides, enrichment analysis identified four highlighted biological processes related to the 31 candidate genes. The top biological processes are determined as dopamine transport, learning, memory, and monoamine transport.

Among 31 initial genes, 7 were introduced as crucial elements for onset and development in OCD and can be suggested for further investigations. Furthermore, the complex molecular origin of OCD requires high-throughput screening for diagnosis and treatment goals. The findings are a possible valuable source to establish molecular-based diagnostic tools for OCD.

Midkine (MK), a heparin-binding growth factor, is involved in neurological diseases by mediating the inflammatory responses through enhancing the leukocyte migration. The present study assesses the serum concentration of this growth factor among newly developed Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO) patients.

The present research, as a cross-sectional study, was performed at Isfahan University of Medical Sciences, Isfahan City, Iran. All samples were selected from patients who visited Kashani and Alzahra hospitals for two years (2014 to 2016). The MK level was assessed in 80 new MS cases, 80 NMO patients, and 80 healthy subjects. After collecting blood sera samples, MK serum level was measured using the ELISA. The obtained data were analyzed in SPSS.

The Mean±SD MK level was 1038.58±44.73 pg/mL in the MS group, which was significantly higher than the Mean±SD MK level in the NMO (872.62±55.42 pg/mL) and control groups (605.02±9.42 pg/mL).

Overall, these results demonstrated that MK plays a prominent role in inflammatory reactions and neuroautoimmune diseases, especially in MS. So, the MK level may be used for earlier diagnosis and also prevention of disease progression by using a special inhibitor.

Midbrain dopaminergic neurons are involved in various brain functions, including motor behavior, reinforcement, motivation, learning, and cognition. Primary dopaminergic neurons and also several lines of these cells are extensively used in cell culture studies. Primary dopaminergic neurons prepared from rodents have been cultured in both DMEM/F12 and neurobasal mediums in several studies. However, there is no document reporting the comparison of these two mediums. So in this study, we evaluated the neurons and astroglial cells in primary midbrain neurons from rat embryos cultured in DMEM/F12 and neurobasal mediums.

Primary mesencephalon cells were prepared from the E14.5 rat embryo. Then they were seeded in two different mediums ( Dulbeccochr('39')s Modified Eagle Medium/Nutrient Mixture F-12 [DMEM/F12] and neurobasal). On day 3 and day 5, half of the medium was replaced with a fresh medium. On day 7, β3-tubulin-, GFAP (Glial fibrillary acidic protein)- and Tyrosine Hydroxylase TH-positive cells were characterized as neurons, astrocytes, and dopaminergic neurons, respectively, using immunohistochemistry. Furthermore, the morphology of the cells in both mediums was observed under light microscopy on days 1, 3, and 5.

The cells cultured in both mediums were similar under light microscopy regarding the cell number, but in a neurobasal medium, the cells have aggregated and formed clustering structures. Although GFAP-immunoreactive cells were lower in neurobasal compared to DMEM/F12, the number of β3-tubulin- and TH-positive cells in both cultures was the same.

This study’s findings demonstrated that primary midbrain cells from the E14.5 rat embryo could grow in both DMEM/F12 and neurobasal mediums. Therefore, considering the high price of a neurobasal medium, it can be replaced with DMEM/F12 for culturing primary dopaminergic neurons.

Profilin1 (PFN1) is a ubiquitously expressed protein known for its function as a regulator of actin polymerization and dynamics. A recent discovery linked mutant PFN1 to Amyotrophic Lateral Sclerosis (ALS), which is a fatal and progressive motor neuron disease. We have also demonstrated that Gly118Val mutation in PFN1 is a cause of ALS, and the formation of aggregates containing mutant PFN1 may be a mechanism for motor neuron death. Hence, we were interested in investigating the aggregation of PFN1 further and searching for co-aggregated proteins in our mouse model overexpressing mutant PFN1.

We investigated protein aggregation in several tissues of transgenic and no-transgenic mice using western blotting. To further understand the neurotoxicity of mutant PFN1, we conducted a pull-down assay using an insoluble fraction of spinal cord lysates from hPFN1G118V transgenic mice. For this assay, we expressed His6-tagged PFN1WT and PFN1G118V in E. coli and purified these proteins using the Ni-NTA column.

In this study, we demonstrated that mutant PFN1 forms aggregate in the brain and spinal cord of hPFN1G118V mice, while WT-PFN1 remains soluble. Among these tissues, spinal cord lysates were found to have PFN1 bands at higher molecular weights recognized with anti-PFN1. Moreover, the pull-down assay using His6-PFN1G118V showed that Myelin Binding Protein (MBP) was present in the insoluble fraction.

Our analysis of PFN1 aggregation in vivo revealed further details of mutant PFN1 aggregation and its possible complex formation with other proteins, providing new insights into the ALS mechanism.

Semaphorin 3A (Sema 3A) is a secreted protein, which plays an integral part in developing the nervous system. It has collapse activity on the growth cone of dorsal root ganglia. After the development of the nervous system, Sema 3A expression decreases. Neuropilin 1 is a membrane receptor of Sema 3A. When semaphorin binds to neuropilin 1, the recruitment of oligodendrocyte precursor cells to the demyelinated site decreases. In Multiple Sclerosis (MS), Sema 3A expression increases and inhibits oligodendrocyte precursor cell differentiation. Therefore, the remyelination of axons gets impaired. We hypothesized that the function of Sema 3A could be inhibited by neutralizing its binding to membrane NRP1. 

we cloned a soluble form of mouse Neuropilin 1 (msNRP1) in a lentiviral vector and expressed the recombinant protein in HEK293T cells. Then, the conditioned medium of the transduced cells was used to evaluate the effects of the msNRP1 on the inhibition of Sema 3A-induced growth cone collapse activity. Dorsal root ganglion explants of timed pregnant (E13) mice were prepared. Then, the growth cone collapse activity of Sema 3A was assessed in the presence and absence of msNRP1-containing conditioned media of transduced and non-transduced HEK293T cells. Comparisons between groups were performed by 1-way ANOVA and post hoc Tukey tests.

msNRP1 was successfully cloned and transduced in HEK293T cells. The supernatant of transduced cells was concentrated and evaluated for the production of msNRP1. ELISA results indicated that transduced cells secreted msNRP1. Growth cone collapse assay showed that Sema 3A activity was significantly reduced in the presence of the conditioned medium of msNRP1-transduced HEK293T cells. Conversely, a conditioned medium of non-transduced HEK293T cells could not effectively prevent Sema 3A growth cone collapse activity.

Our results indicated that msNRP1 was successfully produced in HEK293T cells. The secreted msNRP1 effectively prevented Sema 3A collapse activity. Therefore, msNRP1 can increase remyelination in MS lesions, although more studies using animal models are required.

Fingolimod is the first confirmed oral immune-modulator to treat Relapsing-Remitting Multiple Sclerosis (RRMS). This study aimed to investigate the safety and efficacy of fingolimod therapy in Iranian patients with RRMS.

In our trial, 50 patients resistant to conventional interferon therapy were assigned to receive fingolimod 0.5 mg per day for 12 months. The number of Dadolinium (Gd)-enhanced lesions, enlarged T2 lesions, and relapses over 12 months were considered as endpoints and compared to baseline. Liver biochemical evaluations and lymphocyte count were done at baseline and in months 3, 6, and 12 of the study. Patients were also monitored for possible cardiovascular events within the first 24 h and other side effects routinely.

Among the patients who completed the trial, the number of Gd-enhanced and enlarged T2 lesions over 12 months significantly decreased (P=0.03 and P<0.001, respectively). The proportion of relapse-free patients was higher compared to the onset of fingolimod administration. There were no significant alterations in the Expanded Disability Status Scale (EDSS) scores. A slight, transient increase was recorded in liver enzymes among the participants. Lymphocyte count reduced by 61% at month 1 and displayed a gradual increase until month 12. No bradycardia and macular edema were recorded.

These findings indicate an effective first-line fingolimod therapy for the first time in Iranian patients with RRMS. The decrease in the number of new attacks and the amelioration of MRI lesions were the benefits of fingolimod therapy, suggesting that it is preferred to other medicines to treat RRMS in Iran.

Methamphetamine (MA) acts as a powerful oxidant agent, while Rosmarinic Acid (RA) is an effective herbal antioxidant. Oxidative stress-mediated by MA results in apoptosis, and caspase-3 is one of the critical enzymes in the apoptosis process. MA can epigenetically alter gene regulation. In this paper, to investigate the effects of RA on MA-mediated oxidative stress, changes in the level of casp3a mRNA were demonstrated in zebrafish.

The animals were grouped in 3 treatment conditions for the behavioral test: control, MA, MA pretreated by RA, and 6 treatment conditions for the molecular test: control, RA, MA, MA co-treated with RA, MA co-treated with RA/ZnO/chitosan nanoparticle, and ZnO/chitosan nanoparticle. Then molecular and behavioral investigations were carried out, and critical comparisons were made between the groups. MA solution was prepared with a concentration of 25 mg/L, and RA solution was prepared by DPPH test with the antioxidant power of about 97%. Each solution was administered by immersing 20 zebrafish for 20 minutes, once per day for 7 days. The level of casp3a mRNA was quantified by using qRT-PCR. One-sided trapezoidal tank diving test was applied to study behavioral alterations.

The qPCR analysis demonstrated the high potential of RA/ZnO/chitosan in counteracting the MA-mediated elevation in casp3a mRNA level. Based on the diving test results of MA-treated fish, MA was found to be anxiolytic compared to the control. While the resulted diving pattern of the MA-treated animals pretreated by RA was novel and different from both the control and MA-treated groups.

The potential of RA combined with a suitable nanoparticle against MA-induced oxidative stress was supported. The high efficiency of ZnO/chitosan in increasing RA penetration to the brain cells was evident. MA at a dose of 25 mg/L is anxiolytic for zebrafish. However, the molecular mechanisms involved in these processes should be studied.

Minocycline has anti-inflammatory, anti-apoptotic, and anti-oxidant effects. Preclinical data suggest that minocycline could be beneficial for treating common neurological disorders, including Parkinson disease and multiple sclerosis.

In this study, the effects of minocycline on harmaline-induced motor and cognitive impairments were studied in male Wistar rats. The rats were divided into four groups of ten animals each. Harmaline was used for the induction of Essential Tremor (ET). Minocycline (90 mg/kg, IP) was administered 30 minutes before the saline or harmaline. Tremor intensity, spontaneous locomotor activity, passive avoidance memory, anxiety-related behaviors, and motor function were assessed in the rats. 

The results showed that minocycline could recover tremor intensity and step width but failed to recuperate the motor balance. The memory impairments observed in harmaline-treated rats were somewhat reversed by administration of minocycline. The cerebellum and inferior olive nucleus were studied for neuronal degeneration using histochemistry and transmission electron microscopy techniques. Harmaline caused ultrastructural changes and neuronal cell loss in inferior olive and cerebellar Purkinje cells. Minocycline exhibited neuroprotective changes on cerebellar Purkinje cells and inferior olivary neurons.

These results open new therapeutic perspectives for motor and memory impairments in ET. However, further studies are needed to clarify the exact mechanisms.

Ensuring an adequate Depth of Anesthesia (DOA) during surgery is essential for anesthesiologists. Since the effect of anesthetic drugs is on the central nervous system, brain signals such as Electroencephalogram (EEG) can be used for DOA estimation. Anesthesia can interfere among brain regions, so the relationship among different areas can be a key factor in the anesthetic process. 

In this paper, by combining the Wiener causality concept and the conditional mutual information, a nonlinear effective connectivity measure called Transfer Entropy (TE) is presented to describe the relationship between EEG signals at frontal and temporal regions from eight volunteers in three anesthetic states (awake, unconscious and recovery). This index is also compared with Granger causality and partial directional coherence methods as common effective connectivity indexes. 

Based on a statistical analysis of the probability predictive value and Kruskal-Wallis statistical method, TE can effectively fallow the effect-site concentration of propofol and distinguish the anesthetic states well, and perform better than the other effective connectivity indexes. This index is also better than Bispectral Index (BIS) as commercial DOA monitor because of the faster response and higher correlation with the drug concentration effect-site, less irregularity in the unconscious state and better ability to distinguish three states of anesthestesia.

TE index is a confident indicator for designing a new monitoring system of the two EEG channels for DOA estimation.

Generalized Anxiety Disorder (GAD) is one of the most common anxiety disorders that has significant adverse effects on social functioning, occupational/academic performance, and daily living. This study aimed to evaluate the effect of Quantitative Electroencephalography (QEEG)-based Neurofeedback (NFB) therapy on anxiety, depression, and emotion regulation of people with GAD.

This research is a quasi-experimental study with a pre-test/post-test/follow-up design and a control group. The study participants were 29 college students with GAD living in Zanjan City, Iran, who were selected using a convenience sampling method. Then, they were randomly divided into two groups of intervention (n=15) and control (n=14). The protocol of NFB therapy was designed based on the QEEG method. The intervention group received QEEG-based NFB therapy for 8 weeks (20 sessions, 2 sessions per week, each session for 45 min), while the control group received no intervention. The samples were surveyed and measured by using a 7-item GAD scale, Emotion Regulation Questionnaire (ERQ), 21-item Depression, Anxiety, and Stress Scale (DASS), and Structured Clinical Interview for DSM (SCID) before and after the intervention and then at a 3-month follow-up. The collected data were analyzed in SPSS software V. 22 using univariate ANCOVA and repeated measures ANOVA.

The within-subjects effect of time (pre-test, post-test, and follow-up) was statistically significant (P=0.031). The intervention group showed significant changes in the post-test and follow-up phases in comparison with the control group. The anxiety and depression levels of patients reduced significantly (P=0.001), and their emotion regulation improved (P=0.001) after the intervention, and they remained unchanged in the follow-up period.

QEEG-based NFB therapy can reduce anxiety and depression and improve emotion regulation in patients with GAD.

To investigate the effects of predictable and unpredictable external perturbations on cortical activity in healthy young and older adults.

Twenty healthy older and 19 healthy young adults were exposed to predictable and unpredictable external perturbations, and their cortical activity upon postural recovery was measured using a 32-channel quantitative encephalography. The absolute spectral power and coherence z-scores of cortical waves were analyzed through a 3-way mixed ANOVA.

During postural recovery from predictable perturbations, older adults exhibited higher frontoparietal beta power and higher alpha and beta coherence during the late-phase recovery than the young individuals. After unpredictable perturbations, the older group showed lower alpha power in the early phase and higher beta power in the late phase as compared to the young group. Results for the group × time and group × location interactions in the older group showed a higher alpha and beta coherence over the late phase, a higher alpha coherence in F3−P3 and F4−P4 regions, and a higher beta coherence in the F4−P4 region compared to the younger group.

Our results revealed that the cortical activation after external perturbations increases with aging, particularly in frontoparietal areas. A shift from automatic (subcortical level) to attentional (cortical level) processing may reflect the contribution of attentional resources for postural recovery from an external threat in older individuals.