Basic and Clinical Neuroscience
Volume:12 Issue: 5, Sep-Oct 2021

In this systematic review, we will discuss the change of stroke incidence during the COVID-19 pandemic period and the proposed mechanisms of the relationship between SARS-CoV-2 and stroke.

Web of Science, PMC/Medline, and Scopus databases were searched until July 2020 without time and language limitations. After quality assessment, 22 articles were included in this study.

Based on the results, it is impossible to conclude any definite relationship between the rising or decreasing stroke frequency or the shift in the ischemic and hemorrhagic ratio and SARS-CoV-2 infection. However, it appears that SARS-CoV-2 infection has some correlation with stroke. The supposed mechanisms for the SARS-CoV-2-related hemorrhagic stroke include 1) SARS-CoV-2-related vasculopathy with the endothelial damage of small vessels, 2) viral infection-induced platelet dysfunction or thrombocytopenia, and 3) activation of the proinflammatory cascade leading to coagulopathy. The helpful strategies are receiving therapeutic anticoagulation for high D-dimer or a known thrombus due to SARS-CoV-2 infection, as well as using extracorporeal membrane oxygenation (ECMO) in some patients. Furthermore, the possible mechanisms for the SARS-CoV-2-related ischemic stroke include 1) dysregulation of angiotensin-converting enzyme 2 (a key host cellular receptor for SARS-CoV-2)-related physiologic functions, 2) endothelial cell damages, 3) thrombo-inflammation, and 4) coagulopathy and coagulation abnormalities related to SARS-CoV-2 infection. 

A better understanding of the SARS-CoV-2 pathogenesis and its relation to neurologic abnormalities such as stroke can help to design new therapeutic approaches.

Computer games as an interactive media play a significant role in the cognitive and behavioral health of the players. Computer games have either positive or negative effects on cognitive indices among players. They also directly influence the lifestyle and quality of life of children, adolescents, and young adults. The present study aimed to evaluate the short-term effects of the brain teaser game on players.

Among 45 male volunteers, 40 subjects with an average age of 20 years were recruited and divided into two groups: the experimental group and the control group. All required tests were conducted before and after the intervention (playing the game) on the experimental group. Also, the same tests were performed on the control group, in which the participants were not allowed to play the game. All participants completed a questionnaire comprised demographic characteristics and specific information regarding the game (e.g., game style and hours spent on playing the game). The saliva samples were collected to measure levels of cortisol and α-amylase. The salivary α-amylase (sAA) and cortisol levels were analyzed using the relevant ELISA kits. The cognitive tests were performed using PASAT software before and after the game to assess the perceptual-cognitive abilities of the players. The brain waveforms were acquired by a 14-channel Emotiv brain signal recording device before and after the game. Data analysis was conducted in R and MATLAB software.

PASAT test suggested that mental health and sustained attention were significantly improved after the intervention. In addition, the sAA and salivary cortisol levels were significantly higher before the intervention. The results of the brainwave analysis revealed that stress index and attention were significantly higher before the intervention.

Findings of the present study suggest that brain teaser games positively influence the central nervous system and activate stress path, leading to changes in brain signals and subsequently improved cognitive elements, such as attention among players.

A brief neuroscience-informed psychoeducation program (Neuroscience-Informed Psychoeducation for Recovery [NIPER]) was developed to promote awareness (metacognition) in the main cognitive domains affected by drug and alcohol use to increase willingness to invest time and effort in the brain and cognition recovery process. The primary aim of this pilot study was to determine the feasibility and acceptability of the NIPER program and its potential effectiveness in increasing metacognition, psychological wellbeing, and willingness for the brain and cognition recovery programs among patients with Substance Use Disorders (SUDs).

A total of 56 patients with SUDs were recruited from four outpatient treatment centers in Tehran City, Iran. They participated in four 90-min weekly sessions delivered adjunct to their routine treatment. The program’s effectiveness was measured in terms of metacognition and psychological wellbeing at baseline and the end of the program. The rate of adherence and participation and willingness to continue with brain and cognition recovery programs were measured as feasibility outcomes.

A total of 51 participants completed the study. Compared to the baseline assessments, patients reported more problems in dimensions of attention, memory, inhibitory control, decision making, motor/speech, interoception, insight, and a higher level of psychological wellbeing (t=4.66; P<0.001). In terms of feasibility outcomes, the adherence and participation rates were found above 85%. Most participants expressed their high willingness to continue the brain and cognition recovery programs (86.2%) and would introduce NIPER to their peers (98%).

Considering the pilot results in terms of feasibility and preliminary effectiveness of NIPER in the clinical context of addiction treatment, we think that NIPER is a potentially beneficial intervention to be offered to people with SUD. It would increase their awareness and engage them in the brain and cognition recovery process. However, the clinical efficacy of the intervention should be tested in future randomized clinical trials.

Previous studies have shown that physical and psychological dependence and the vulnerability to relapse are still present during MMT. Thus, this study examined whether Enriched Environment (EE) would attenuate anxiety, depressive, and obsessive-compulsive-like behaviors, as well as voluntary morphine consumption following Methadone Maintenance Treatment (MMT) in morphine withdrawn rats.

The rats were injected bi-daily doses (10 mg/kg, 12-h interval) of morphine for 14 days. Then, the rats were reared in a Standard Environment (SE) or EE for 30 more days during morphine withdrawal, simultaneous with receiving MMT. The rats were tested for anxiety (the Elevated Plus Maze [EPM]) and depression (Sucrose Preference Test [SPT]), Obsessive-Compulsive Disorder (OCD) as grooming behavior, and voluntary morphine consumption using a Two-Bottle Choice (TBC) paradigm.

The findings revealed that EE experience in morphine withdrawn rats under MMT significantly increased the EPM open-arm time and higher sucrose preference than SE rats. Also, we found that the EE decreased the self-grooming behavior and morphine preference ratio in morphine withdrawn rats receiving MMT compared to the SE group.

We conclude that exposure to EE decreased methadone-induced anxiety, depressive and OCD-like behaviors, and voluntary morphine consumption in morphine withdrawn rats under MMT. Thus, the EE seems to be one of the strategies for reducing MMT-induced behavioral dysfunction and the risk of relapse induced by morphine withdrawal.

Neurosphere-free transdifferentiation of bone marrow stem cells into Retinal Pigment Epithelium (RPE) and Retinal Cells (RCs) in vitro could offer an exceptional opportunity to study cell replacement in degenerative eye diseases. Thus, a simple and efficient protocol for retinal cells production from transdifferentiation of rat BMSCs in the neurosphere-free state is reported. 

Extracted BMSCs from hooded pigment rats were exposed to a single-step protocol, including neurosphere-free, containing a cocktail medium that induced transdifferentiation into Retinal Pigment Epithelium (RPE) and retinal cells. 

The results showed morphological differentiation changes in vitro. Also, the expressed retinal pigment epithelium and retinal cell markers, such as retinal orthodenticle homeobox 2 (23.45%), retinal pigment epithelium protein 65 (91.54%), cellular retinaldehyde-binding protein (91.21%), vascular endothelial growth factor (94.79%), rhodopsin (57.19%), glial fibrillary acidic protein (28.33%), and neurofilament 200 (24.55%). 

Overall, these findings showed that a protocol without using basic fibroblast growth factor, epidermal growth factor, and B-27 supplements could generate RPE and retinal cells in vitro.

Erythrophleum Ivorense (EI) is a tree found across tropical Africa. The bark of EI is widely used as hunting poisons for animals and ordeal poison in humans. Eating this plant causes paralysis, respiratory distress, and amnesia. In folklore, these behavioral changes have been attributed to guilt in victims; nonetheless, no scientific evidence supports this claim. Thus, the mechanism of neurotoxicity and behavioral alteration of this plant should be investigated. 

A total of 48 BALB/c male mice were randomly divided into four groups. The three experimental groups were administered an aqueous extract of EI in a single daily dose of 5, 10, and 15 mg/kg bodyweight for 28 days, while the control group received distilled water. Afterward, the motor coordination, learning, memory, and grip strength of the mice were accessed with wire grip, Morris water maze, and inverted wire mesh grid grip tests. Histological staining of brain sections was also carried out. 

At all tested doses, the aqueous extract of EI caused a significant reduction in hanging latency, significantly increased escape latency, and decreased duration of the target platform in the Morris water maze test compared to control. Reduced grip strength was also observed in the test groups compared to the control. Histology revealed dysmorphic and disoriented Purkinje cells and loss of this cell layer of the cerebellum. 

Erythrophleum ivorense administration altered motor coordination, learning and memory, and grip strength in mice dose-dependently. It also caused disruption of granule cells layer, loss of Purkinje cells, and altered cerebellar anatomy leading to motor deficits in mice.

Identifying a potent biomarker for smoking cessation can play a key role in predicting prognosis and improving treatment outcomes. This study aimed to evaluate the contribution of new biomarkers based on the levels of Cotinine (Cot) and carbon monoxide (CO) to the short- and long-term quit rates of nicotine replacement therapies (Nicotine Patch [NP] and Nicotine Lozenge [NL]).

In this prospective interventional study, 124 smokers under treatment with the 5A’s method were selected from an outpatient smoking cessation center in district 18 of Tehran City, Iran. The study was conducted from April 2016 to December 2018. They were divided into NP (n=56) and NL (n=61) intervention groups. The levels of Cot and CO were measured using ELISA and breath analysis at the beginning of the study. Three markers were calculated: Cot/CO, Cot to cigarette per day ratio (Cot/CPD), and CO/CPD. Binary logistic regression models and generalized estimating equations models were analyzed by SPSS software, version 21 to determine the chances of quitting smoking.

Of the NP participants, 30.4% and 19.6% were abstinent after 2 and 6 months, respectively, while NL was found less effective with 19.7% for 2-month follow-up and 13.1% for 6-month follow-up. The 6-month success of quitting attempts was significantly different for the NP participants at the second half of Cot/CO (P=0.029). Of the NL participants, CO/CPD would be a superior predictor for smoking cessation success (P>0.05). 

The findings of this study suggested two markers of Cot/CO and CO/CPD in this order for the optimum treatment outcomes of NP and NL.

The modality of γ-aminobutyric acid type a receptors (GABAA) controls dorsal horn neuronal excitability and inhibits sensory information. This study aimed to investigate the expression of the GABAA receptor and the effects of its agonist muscimol on Wide Dynamic Range (WDR) neuronal activity in the Chronic Constriction Injury (CCI) model of neuropathic pain.

Adult male Wistar rats weighing 200 to 250 g were used to induce CCI neuropathy. Fourteen days after surgery, muscimol (0.5, 1, and 2 mg/kg IP) was injected. Then, the behavioral tests were performed. After that, the animals were killed, and the lumbar segments of the spinal cords were collected for Western blot analysis of the GABAA receptor α1 subunit expression. The electrophysiological properties of WDR neurons were studied by single-unit recordings in separate groups 14 days after CCI.

The outcomes indicated the development of thermal hyperalgesia and mechanical allodynia after neuropathy; nonetheless, the expression of the GABAA receptor α1 subunit did not change significantly. Moreover, the evoked responses of the WDR neurons to electrical, mechanical, and thermal stimuli increased considerably. Fourteen days after CCI, muscimol administration decreased thermal hyperalgesia, mechanical allodynia, and hyper-responsiveness of the WDR neurons in CCI rats. 

The modulation of the spinal GABAA receptors after nerve injury can offer further insights to design new therapeutic agents to reduce neuropathic pain symptoms.

Oxidative stress plays a critical role in the pathogenesis of neurodegenerative and neuropsychiatric disorders. However, its role in suicidal behavior has not been clarified yet. Consequently, we aimed to evaluate the oxidant-antioxidant status in the serum of suicide attempters in Ilam city. 

Fifty suicide attempters and 40 control subjects (volunteers) aged 18-35 years were studied in the current experiment. To consider the oxidant-antioxidant status, serum levels of Malondialdehyde (MDA), Nitric Oxide (NO), Superoxide Dismutase (SOD), and the Total Antioxidant Capacity (TAC) were measured. 

Serum levels of SOD and TAC were significantly lower in the suicide attempters group compared to the controls. Furthermore, serum NO level was significantly higher in the suicide attempters compared to the control groups. Interestingly, the serum level of MDA was significantly lower in the suicide attempters compared to the control groups.

The oxidative stress without MDA elevation, detected in suicide attempters, can be considered a biochemical hallmark in suicide behavior.

Obsessive-Compulsive Disorder (OCD) is one of the most common debilitating mental disorders with a prevalence rate of 2% to 3% in the general population. Previous studies have indicated abnormalities in the dorsolateral prefrontal cortex (DLPFC) of OCD patients; thus, we decided to use transcranial Direct Current Stimulation (tDCS) to decline these patients’ symptoms.

A total of 24 patients with OCD participated in this study with the hope of improvement after the application of tDCS. The subjects were randomly assigned to three groups of Sham, Right DLPFC, and Left DLPFC. tDCS was applied for five consecutive days and in each session, patients were subjected to 2 mA current flow for two 15 minutes followed by a 10-minute rest in between (every session lasted for 40 minutes).

Subsequently, the changes in obsessive-compulsive level and cognitive functions were evaluated via Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Depression, Anxiety, and Stress Scale 21 (DASS-21) by comparing the results before (pre-test) and after (post-test) tDCS treatment.

Ultimately, the scores of the Yale-Brown scale in the Left DLPFC group showed significant changes after treatment with tDCS (mean difference compared to the sham group: -6.18 and P≤0.05). Hereupon, this study demonstrated that transcranial direct current stimulation may cause improvements in symptoms of OCD.

Caffeine and nicotine are the most widely consumed psychostimulants worldwide. Although the effects of each drug alone on the central nervous system have been studied extensively, the literature on the neurochemical and electrophysiological effects of their combined treatments is scarce. The present study investigated the cortical electrophysiological and neurochemical alterations induced by acute administration of caffeine and nicotine in rats. 

The rats received caffeine and nicotine at a 1-hour interval between the two treatments. 

Caffeine and nicotine administration resulted in a significant decrease in the concentrations of cortical amino acid neurotransmitters, namely glutamate, aspartate, glycine, and taurine, while γ-aminobutyric acid (GABA) significantly increased. Increased cortical lipid peroxidation and reduced glutathione and nitric oxide levels and acetylcholinesterase and Na⁺/K⁺-ATPase activities were also observed. The Electroencephalogram (EEG) showed an increase in delta frequency power band, whereas theta, beta-1, and beta-2 decreased after caffeine and nicotine treatment. 

These findings suggest that caffeine and nicotine adversely exacerbate their stimulant effects manifested by the EEG changes mediated by increasing cholinergic transmission and disturbing the balance between the excitatory and inhibitory amino acids leading to oxidative stress.

Aggression and impulsivity are some of the behavioral symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). Neurofeedback (NF) training has been suggested as a promising treatment in these children. This study aimed to investigate the effect of NF training on aggression and impulsivity in schoolchildren with ADHD. 

A total of 40 male elementary school children with ADHD (aged 11.17±0.97 years) were randomized into the NF and sham groups. The NF group received 12 NF training sessions, each taking about 60 minutes for six consecutive weeks (twice a week), based on the Hammond protocol. The subjects’ parents were questioned to evaluate the outcomes, including aggression and impulsivity, using the Buss-Perry Aggression Questionnaire (BPAQ) and Barratt Impulsiveness Scale (BIS).

After the intervention, in the NF group, the BPAQ score changed from 87.60±9.33 to 81±7.23 and the BIS score from 94.7±7.25 to 88.05±5.4, which were significant (P=0.001). The results indicated the large effect size of NF on aggression and impulsivity in ADHD.

Our findings suggest NF training as a clinically applicable method for decreasing aggression and impulsivity, also support concurrent use of medication and NF training in children with ADHD.

Guillain-Barre Syndrome (GBS) is an autoimmune acute inflammatory demyelinating polyneuropathy usually elicited by an upper respiratory tract infection. Several studies reported GBS associated with Coronavirus Disease 2019 (COVID-19) infection. In this study, we described nine GBS patients following the COVID-19 vaccine.

In this study, nine patients were introduced from six referral centers for neuromuscular disorders in Iran between April 8 and June 20, 2021. Four patients received the Sputnik V, three patients received the Sinopharm, and two cases received the AstraZeneca vaccine. All patients were diagnosed with GBS evidenced by nerve conduction studies and/or cerebrospinal fluid analysis.

The median age of the patients was 54.22 years (ranged 26-87 years), and seven patients were male. The patients were treated with Intravenous Immunoglobulin (IVIg) or Plasma Exchange (PLEX). All patients were discharged with some improvements.

The link between the COVID-19 vaccine and GBS is not well understood. Given the prevalence of GBS over the population, this association may be coincidental; therefore, more studies are needed to investigate a causal relationship.