Highlights 
● Invasive and non invasive methods for presurgical language mapping in intractable epilepsy.
● Functional Magnetic Resonance Imaging (fMRI).
● Designing language tasks for mapping.
● Persian language tasks.
Plain Language Summary 
People with intractable epilepsy can be treated by brain surgery. Their language and other cognitive abilities must be reserved after surgery, therefore, precise mapping is needed and it requires well-designed and standard tasks. Nowadays, functional magnetic resonance imaging is used as an invasive method for brain mapping. we reviewed presurgical language mapping tasks used in fMRI for patients with epilepsy. 

Highlights 
● Melatonin markedly diminished astrocyte reactivity following traumatic brain injury.
● Melatonin treatment reduced the number of apoptotic neurons.
● Melatonin reduces astrocyte reactivity and cell death in a dose-independent pattern.
Plain Language Summary 
Annually, many people lose their lives due to brain injury worldwide. Brain injury induces an almost immediate response from glial cells. Also, activation of glial cells may result in secondary neuronal damage. Melatonin is known as an anti‐inflammatory agent, and it has been reported to exert neuroprotection. 

Highlights 
● Seven genes were suggested to have topological features in the Obsessive-Compulsive Disorder (OCD) interaction network.
● Dopamine transport, learning, memory, and monoamine transport were the critical contributing biological processes in the OCD network.
● ESR1 could play an indenciple role in a specific subtype of OCD for women. 
● The presence of OCD in different subtypes could be linked to the combination of malfunction of gene groups. 
Plain Language Summary 
The results of this study suggest that topological information of interactome profile of OCD reported genes from genetic studies; however, it is in its initial phase. Our PPI network analysis can serve as a paradigm for later experiments such as genomic, proteomic, and metabolomic investigations.

Highlights 
● The mean Midkine (MK) level in Multiple Sclerosis (MS) patients is higher than Neuromyelitis Optica (NMO) patients and the healthy control group.
● The level of MK is higher in the NMO group compared with the healthy one. 
● The healthy subjects have the lowest mean of MK level compared with the other groups.
● Sex and age have no significant association with the MK level.
Plain Language Summary 
Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO) are two distinct diseases with similar clinical symptoms, so it is necessary to distinguish these disorders from each other. Although there are many studies to find biomarkers for this goal, only a few of them have been validated for routine clinical practice. Because of the inflammatory nature of MS and NMO, our research group claims to evaluate the utility of Midkine (MK) as a heparin-binding growth factor that is implicated in inflammation. Our results demonstrated that MS patients have higher MK levels compared to NMO patients and the healthy participants. Also, sex and age have no significant association with the MK level. Therefore, MK may be a reliable biological marker in differentiating between MS and NMO.

Highlights 
● Rat primary mesencephalon neurons were cultured in DMEM/F12 and neurobasal mediums.
● GFAP-immunoreactive cell number was lower in neurobasal compared to DMEM/F12.
● The number of β3-tubulin- and TH-positive cells was the same in both cultures.
● Primary midbrain cells can grow in both DMEM/F12 and neurobasal mediums.
Plain Language Summary 
Dopaminergic neurons are involved in various brain functions, like motor behaviors, and are extensively used in cell culture studies. In this study, we compared dopaminergic neurons and glial cells from mesencephalon tissue of rat embryos in DMEM/F12 and neurobasal mediums. The morphology of the cells in both mediums was observed under light microscopy on day 7 after culturing. The number of the cells was similar in both mediums, however, the cells in the neurobasal medium formed aggregated clustering structures. As expected, the number of GFAP-immunoreactive cells was lower in neurobasal compared to DMEM/F12, but the number of β3-tubulin-positive cells and tyrosine hydroxylase-positive neurons in both cultures was the same. These findings demonstrated that rat primary midbrain cells can grow in both DMEM/F12 and neurobasal mediums. Therefore, considering the costly price of a neurobasal medium, DMEM/F12 can be used for culturing dopaminergic neurons.

Highlights 
● Recombinant His6-tagged PFN1 proteins were purified for pull-down assay.
● Mutant PFN1 forms aggregate and complexes with myelin binding protein in hPFN1G118V mice.
● Misfolding of mutant PFN1 protein occurs earlier, and aggregation is the final product.
Plain Language Summary 
Amyotrophic Lateral Sclerosis (ALS) or motor neuron disease affects 3-5 per 100000 people worldwide. Despite the discovery of causative genes accounting for ~50% of familial ALS, the mechanism of how and why motor neurons degenerate has not been fully understood yet. Currently, there are no effective therapies available for patients suffering from this devastating disease. The mutation in the PFN1 gene, encoding PFN1 protein, was recently discovered as a new cause of ALS, and its study may provide new clues on how nerve cells will die in ALS. PFN1 protein is of great interest for its crucial functions contributing to neuronal morphology and long axons. In this report, our results showed that ALS-linked mutant PFN1 protein forms clumps in the CNS region of ALS-linked mouse models that may damage the neurons and push them to die. We also found that clumping of PFN1 may form complexes with other essential proteins that may further cause stress and damage to neurons.

Highlights 
● A soluble form of mouse Neuropilin1 (msNRP1) was cloned in a lentiviral vector.
● msNRP1 was successfully secreted by the transduced HEK293T in the supernatant.
● msNRP1-containing supernatant inhibited growth cone collapse activity of semaphorins 3A.
Plain Language Summary 
Multiple Sclerosis (MS) is an inflammatory disease of the central nervous system. In MS, axons of neuronal cells become demyelinated, and the remyelination process is also defective. Oligodendrocyte precursor cells must survive, proliferate, and migrate towards demyelinated neurons and differentiate into mature oligodendrocytes to produce myelin and repair the neurons. Semaphorin 3A (Sema 3A) is a molecule that reduces the remyelination by preventing oligodendrocyte precursor cells from proliferating, migrating towards lesions, and differentiating into mature oligodendrocytes. We successfully produced mouse soluble Neuropilin 1 (msNRP1) that can bind Sema 3A and inhibit its activity. In other words, the msNRP1 was used to inhibit the activity of Sema 3A. Neural cells of dorsal root ganglia were cultured in the presence of Sema 3A with and without msNRP1. We observed that when msNRP1 was added to the neuronal cells culture, the growth cones could form. On the other hand, the growth cones collapsed when msNRP1 was not added to the cultures. This finding is promising in outcome of MS treatment. Remyelination is defective in MS patients, and axons are progressively demyelinated. Finding a molecule that can prevent demyelination and enhance remyelination will be of great importance for MS treatment and improvement of their condition.

Highlights 
● The number of relapses considerably decreases in the patients receiving long-term fingolimod. 
● Fingolimod ameliorates magnetic resonance imaging lesions over the 12 months of its administration.
● No serious cardiovascular and macular edema was reported.
● Lymphocyte count and liver enzyme profile are affected by fingolimod administration
Plain Language Summary 
Fingolimod is an FDA-approved medication. It is administrated by neurologists for treating a specific type of multiple sclerosis called Relapsing-Remitting Multiple Sclerosis (RRMS). According to the clinical experiments conducted in the United States and Europe, fingolimod administration is preferred to other medications in terms of side effects and efficacy. In Iran, therapists have no reliable evidence by which they can track the effects of fingolimod on patients. The present study aimed to investigate the safety and efficacy of fingolimod in Iranian patients with RRMS and compare the results (effects and side effects) with other available therapies. Fifty patients were enrolled in the study and assigned to receive fingolimod 0.5 mg per day for 12 months. Magnetic Resonance Imaging (MRI) evaluations, blood sample analysis, and continuous monitoring were performed on the patients who completed the study. The considerable differences observed in this investigation between the beginning and end of the follow-up period supported the effective first-line fingolimod therapy for the first time in Iranian patients with RRMS. A decrease in the number of new attacks, amelioration of MRI lesions, and the protection against brain volume decline were the benefits of fingolimod therapy, suggesting that it is preferred to other therapies to treat RRMS in Iran.

Highlights 
● Methamphetamine (MA) induces excess casp3a transcript in the brain tissue in zebrafish.
● Immediate effect of chronic exposure to 25 mg/L MA is anxiolytic for zebrafish.
● Rosmarinic Acid (RA) counteracts the effects of MA-mediated oxidative stress.
● RA alone does not reduce the anxiolytic effects of MA and even enhances it.
● ZnO/chitosan nanoparticles increase RA penetration to the blood-brain barrier as fast as MA.
Plain Language Summary 
Methamphetamine (MA) called ice or crystal in streets, is a drug of abuse. It has been associated with a variety of neurotoxic effects including oxidative stress, which leads to characteristic cell changes and death. The caspase-3 enzyme is one of the key enzymes of this process. There are storage forms of inactive Caspase-3 in any cell called procaspase-3. It’s been demonstrated previously that MA treatment causes activation of the procaspase-3 resource. The present study was undertaken to investigate whether MA can change the regulation of Caspase-3 gene expression and increase the synthesis of casp3a mRNA in zebrafish. qRT-PCR results demonstrated that MA increases the casp3a mRNA levels up to 18-fold compare to the control group. We were curious to know whether treatment by an antioxidant solution can counteract MA-mediated oxidative stress. So in the second part of this research, we investigated the herbal antioxidant molecule, Rosmarinic Acid (RA). Since the penetration of RA across the Blood-Brain Barrier is not as fast as MA, RA was combined with ZnO/chitosan nanoparticles and then provided to zebrafish as an animal model. The qRT-PCR analysis demonstrated the high potential of RA/ZnO/chitosan in counteracting the MA-mediated elevation in the casp3a mRNA level and brought it back much closer to the level of the control group (2.8-fold). On the other hand, zebrafish is known as a non-mammalian anxiety model system. The immediate effects of treatment of RA on MA-mediated psycho-behaviors were studied by applying the one-sided trapezoidal tank diving test. The diving test of MA-treated zebrafish resulted that the dose of 25 mg/l of MA was anxiolytic compared to the test of saline-treated zebrafish as the control. But the diving pattern of the zebrafish exposed to RA as well as MA was novel and varied from both the control and MA-treated groups. The diving pattern was not similar to any of them and even the stress and speed of diving were less than the MA-treated group.

Highlights 
● Harmaline caused ultrastructural changes and cell loss in IO and Purkinje cells.
 ● Minocycline reversed passive avoidance learning impairment induced by harmaline.
● Minocycline typically ameliorated harmaline-induced tremors. 
● Minocycline exhibited neuroprotective effects on Purkinje cells and IO neurons.
Plain Language Summary 
Tremor as a rhythmic and sinusoidal movement occurs repeatedly in one or more bodies. It is a common disabling symptom of many motor-related disorders such as Parkinson’s disease, Essential Tremor (ET), Multiple sclerosis, and Huntington disease. Patients with ET have other motor problems which imply cerebellar impairment, such as gait ataxia and eye movement abnormalities as well as non-motor conditions, including cognitive, psychiatric, and sensory abnormalities. According to minocycline ameliorating effect on neurodegenerative diseases, the goal of this study was to assess the possible neuroprotective effects of minocycline on motor and cognitive deficits induced by harmaline in the experimental rat model of ET. The rats were randomly divided into four groups (Saline, Minocycline, Harmaline, and Harmaline + minocycline). Each group went through five different behavioral studies which were performed 30 min after harmaline injection with sequentially 15 min rest intervals among each assay in the following order: tremor score assessment, open field test, footprint, rotarod, wire grip, and passive avoidance task. The results showed that pretreatment with minocycline improved tremor status and memory deficit in the rat’s model of tremor induced by harmaline. The memory impairments observed in harmaline-treated rats were somewhat reversed by administration of minocycline. Minocycline exhibited neuroprotective changes on cerebellar Purkinje cells and inferior olivary neurons. However, minocycline seems to act as a neuroprotective agent to improve tremor severity, gait width disturbance, and memory retrieval impairments induced by harmaline. 

Highlights 
● Propose transfer entropy to describe the relationship between EEG signals at frontal and temporal.
● Transfer entropy can effectively fallow the effect-site concentration of propofol.
● Our index is better than the Bispectral index as a commercial DOA monitor.
Plain Language Summary 
Depth of anesthesia (DOA) estimation is the main problem for anesthesiologists to maintain the appropriate level of anesthesia during surgery so that it prevents the possibility of unwanted consciousness and long-term recovery. This study shows that the nonlinear effective connectivity index, called transfer entropy (TE) between pair signals of EEG at frontal and temporal regions can trace effectively the changes in propofol drug effect. TE index is also better than BIS as a single channel commercial index in the clinical setting due to a faster response and a higher correlation with the drug concentration effect-site, less irregularity in the unconscious state, and ultimately has a better ability to discriminate between the three states of anesthesia. Thus, the TE index is a confident effective connectivity indicator for designing a new monitoring system of two EEG channels for the depth of anesthesia estimation.

Highlights 
● Electroencephalography-Based Neurofeedback Therapy is effective in reducing the signs and symptoms of generalized anxiety disorder.
● Electroencephalography-Based Neurofeedback Therapy is effective in reducing the signs and symptoms of depressive disorder.
● Electroencephalography-Based Neurofeedback Therapy improved emotion regulation in people with generalized anxiety disorder.
Plain Language Summary 
Generalized Anxiety Disorder (GAD) is one of the most common anxiety disorders that have significant adverse effects on social functioning, occupational/academic performance, and daily living. The pathological understanding of neurological and psychiatric states has been considered in recent decades, and significant results have been reported on Quantitative Electroencephalography (QEEG) of these disorders. QEEG is a method for examining brain waves, which involves using computers and power spectral analysis of brain waves. In this study, we wanted to evaluate the Effect of Quantitative Electroencephalography-Based Neurofeedback Therapy on Anxiety, Depression, and Emotion Regulation in People with Generalized Anxiety Disorder. The results showed that Electroencephalography-Based Neurofeedback Therapy affected psychological disorders.

Highlights 
● In older adults, the cortical activation, particularly in frontoparietal areas, increases after external perturbations.
● Postural recovery in response to external perturbations requires attentional resources. 
● Attentional demands associated with postural recovery may increase the risk of falling among older adults. 
Plain Language Summary 
Cortical activity in response to external perturbations was compared between 20 healthy older adults and 19 healthy young adults using encephalographic data. The absolute power and coherence of cortical waves were analyzed after predictable and unpredictable perturbations. Our results showed higher frontoparietal beta power in both predictable and unpredictable perturbations and lower alpha power in unpredictable perturbations in older participants. This finding suggests that when the balance task becomes more difficult, the cortical activity and attentional demands increase significantly. Our findings imply greater cortical activation during postural recovery following external perturbations with increasing age. Compelling evidence on this perspective would potentially pave the way towards adopting neurorehabilitation strategies.