Basic and Clinical Neuroscience
Volume:14 Issue: 4, Jul-Aug 2023

Spinal cord injury (SCI) is characterized by serious both motor and sensory disability of the limbs below the injured segment. It is the most traumatic disorder among central nervous system (CNS) conditions which not only leads to psychological and physical harm to patients but also results in a dramatic loss in the life quality. Many efforts have been developed to find a therapeutic approach for SCI; however, an effective treatment has not yet been found. The lack of effective treatment approach and rehabilitation of SCI underscores the need to identify novel approaches. Tissue engineering associated with stem cells has been recently introduced as an effective treatment approaches for traumatic SCI. Although, low survival rates, immune rejection, cell dedifferentiation, and tumorigenicity have been addressed for tissue engineering. Regenerative medicine is an interdisciplinary field developing and applying tissue engineering, stem cell (SC) therapy, and SC-derived extracellular vesicle therapy that aims to provide reliable and safe ways to replace injured tissues and organs. The application of mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) has recently attracted attention to improve central nervous system dysfunction such as SCI, mainly by promoting neurogenesis and angiogenesis.

In this review article the latest information of SCI improvement using stem cell-derived extracellular vesicles published data in the Web of Science, Scopus, Science Direct and Pub Med databases were collected. 

The data collected show that MSC-EVs, including exosomes, alone or in combination with scaffolds can can regenerate the injured nerve in SCI.

This study summarizes the efficacy of MSC-EVs, including exosomes, alone or in combination with scaffolds in the treatment of SCI and then discusses the therapeutic outcomes observed in SCI experimental models following treatment with MSC-EVs alone or loaded on scaffolds in particular collagen-based scaffolds.

Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease. Beta-amyloid (Aβ)-induced neurotoxicity has a pivotal role in AD pathogenesis; therefore, the modulation of Aβ toxicity is the promising therapeutic approach to control the disease progression. Medicinal plants because of their multiple active ingredients are effective in complex diseases, such as AD. Therefore, several studies have studied medicinal plants to find an effective treatment for AD. Ferulago angulata is a medicinal plant with antioxidant and neuroprotective activity. The present study was done to assess the protective effect of the methanolic extract of Ferulago angulate on Aβ-induced toxicity and oxidative stress in PC12 cells.

The methanolic extract of aerial parts of the plant was prepared by the maceration method. PC12 cells were cultured according to a standard protocol. PC12 cells were incubated for 24 hours with Aβ alone, and Aβ in combination with various concentrations of the F. angulata extract. Cell viability was determined by the methyl thiazole tetrazolium (MTT) assay. Also, reactive oxygen species (ROS) production and the activity of acetylcholine esterase (AChE), glutathione peroxidase (GPx), and caspase-3 enzymes were measured. 

The extract dose-dependently protected PC12 cells against Aβ-induced cell death. Also, Aβ increased ROS production, AChE, and caspase-3 activity, and decreased the GPx activity, which all were ameliorated by F. angulata extract. 

F. angulata extract protects against Aβ-induced oxidative stress and apoptosis. These effects may be due to the antioxidant and anticholinesterase activity of the extract. It is recommended to assess F. angulata extract as an anti-AD agent.

Serotonergic system hyperactivity at 5-HT2A receptors on glutamate neurons in the cerebral cortex is one of the pathways that is theoretically linked to psychosis. In addition to neurotransmitter dysfunction, volumetric studies have revealed the loss of cortical gray matter and ventricular enlargement in patients with schizophrenia, although there is no case-control research on patients with schizophrenia to evaluate echogenicity of raphe nuclei (RN) or diameter of the third ventricle (DTV). To address these issues, the present study assessed midbrain RN, as the main source of brain serotonin, and DTV, as an index of atrophy, by transcranial sonography (TCS) in a group of patients with schizophrenia.

Thirty patients with schizophrenia and 30 controls were assessed by TCS for RN echogenicity and DTV. TCS was done through a temporal bone window via a phased-array ultrasound using a 2.5 MHz transducer in a depth of 14-16 cm. RN echogenicity was assessed by a semi-quantitative visual scale and DTV was measured in the thalamic plane.

Twenty-three patients (76.5%) and 15 controls (50 %) showed hypoechogenicity of RN, which was marginally significant (P=0.06). DTV was on average larger in the experimental group (0.388 cm vs 0.234 cm, P<0.001).

Increased DTV in patients with schizophrenia is consistent with previous neuroimaging findings. However, marginally lower echogenicity of midbrain RN on TCS in schizophrenia is a new finding that supports the serotonin hypothesis of schizophrenia.

The opiate dosage adequacy scale (ODAS) is one of the most common assessment tools in studies on substance use disorders, which evaluates the “adequacy” of opiate medication doses in individuals recruited in maintenance approaches. There is no investigation on the Persian version of this questionnaire in Iran. This research validated a Persian version of the ODAS. 

The Persian version of the ODAS was translated and revised based on the original scale presented by González-Saiz et al. The psychometric characteristics of the ODAS were assessed via direct interviews. Three trained interviewers questioned 250 patients treated in methadone maintenance clinics in Mazandaran Province (Northern Iran) for more than three months. Internal consistency and factor analysis were conducted using SPSS software, version 24.

The internal consistency of ODAS was satisfactory (Cronbach’s α=0.81). Across all items, considerable inter-rater reliability was discovered (kappa values between 0.90 and 1). A four-component structure was produced by the factor analysis that accounted for 77.5% of the total variance. Cronbach’s α coefficients of the four components of Heroin craving and overmedication, Consumption, objective opiate withdrawal symptoms, and subjective opiate withdrawal symptoms were 0.84, 0.91, 0.83, and 0.74, respectively.

The reliability and validity of the Persian version of the ODAS were satisfactory in a sample of methadone maintenance subjects.

The aim of the present study was to examine the effectiveness of acceptance and commitment therapy (ACT) on symptom severity, fear of negative evaluation, quality of life (QoL), and the mediating role of acceptance, cognitive fusion, and value among patients with social anxiety disorder (SAD).

Thirty patients diagnosed with SAD were randomized in the intervention (n=15) or waiting list groups (n=15). The social phobia and Anxiety inventory (SPAI), brief fear of negative evaluation scale (BFNE), World Health Organization quality of life (WHOQoL) scale, social anxiety-acceptance and action questionnaire (SA-AAQ), cognitive fusion questionnaire (CFQ), and valued living questionnaire (VLQ) were administered before, immediately after, and at a one-month follow-up. Repeated measurement design was used in the intervention group to investigate the changes of mediation and outcomes variables in the pre-test, during treatment, and post-test. Twenty-four patients completed the study. Data were analyzed using one-way analysis of covariance (ANCOVA), multivariate analysis of covariance (MANCOVA), and repeated measurements.

There were significant differences between the intervention and waiting list groups in the severity of symptoms (P=0.001), fear of negative evaluation (P=0.002), and QoL (P=0.03), as well as in terms of specific measures of SA-AAQ (P=0.001), cognitive fusion (P=0.001), an important section of VLQ (P=0.001). Repeated measurement results showed that acceptance and action of social anxiety and cognitive fusion had a mediating role in the severity of social anxiety, fear of negative evaluation, and QoL. 

The results indicated the effectiveness of ACT for SAD and highlighted the mediator role of social anxiety, acceptance and action, and cognitive fusion in the severity of SAD.

Investigating an effective controller to shift hippocampal epileptic periodicity to normal chaotic behavior will be new hope for epilepsy treatment. Astrocytes nourish and protect neurons and maintain synaptic transmission and network activity. Therefore, this study explored the ameliorating effect of the astrocyte computational model on epileptic periodicity. 

Modified Morris-Lecar equations were used to model the hippocampal CA3 network. Network inhibitory parameters were employed to generate oscillation-induced epileptiform periodicity. The astrocyte controller was based on a functional dynamic mathematical model of brain astrocytic cells.

Results demonstrated that the synchronization of two neural networks shifted the brain’s chaotic state to periodicity. Applying an astrocytic controller to the synchronized networks returned the system to the desynchronized chaotic state.

It is concluded that astrocytes are probably a good model for controlling epileptic periodicity. However, more research is needed to delineate this effect.

In this research, we investigated any possible effect of receiving hyperbaric oxygen therapy (HBOT) or risperidone on the core symptoms of autism in children diagnosed with autism spectrum disorder (ASD). 

This study was a randomized, controlled clinical trial in Minia and Assiut University hospitals in Egypt with three parallel groups. One hundred and eighty children with autism, aged 5–8 years were divided into three equal groups (n=60). Group 1 (G1) received 40 sessions of HBOT within two months, group 2 (G2) received risperidone (dose: 0.25 mg per day in children weighing less than 20 kg and 0.5 mg per day in cases weighing more) for six months, and group 3 (G3) as the control group, received a placebo for six months. The assessment was done using childhood autism rating scale (CARS) and autism treatment evaluation checklist (ATEC) at the beginning of the study (baseline) and after one year.

The mean total CARS and ATEC scores significantly decreased (improved) by varying degrees in the three groups after a year of follow-up compared to the baseline scores, but the best results were found in G1, G2, and G3, respectively.

Using HBOT or risperidone is effective in treating the core symptoms of autism in children diagnosed with autism spectrum disorder, but using HBOT gives better results than risperidone therapy.

Since the introduction of the Food and Drug Administration (FDA)-approved repetitive transcranial magnetic stimulation (rTMS) intervention in 2008, a breakthrough has been made in treating major depressive disorder (MDD). However, many sessions of treatment and its cost make it inconvenient for those who seek treatment, especially in large cities as well as in developing countries.

A total of 22 patients (out of initial 24 referrals) who met diagnostic and statistical manual of mental disorders, 4th edition (DSM IV) criteria for MDD were enrolled in the study. All subjects had to fail at least one prior treatment for depression. The patients received the FDA-approved protocol of high-frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex. 

Seventeen out of twenty-two cases showed significant improvements after two weeks of treatment. Only six patients continued their treatments for the next two to four weeks.

We have replicated other studies showing that the use of rTMS is effective for many patients with MDD without major side effects and their improvements are measurable mostly after two weeks. Our data highlight the importance of the application of more convenient protocols that require fewer sessions on fewer days to help with compliance and outcome, particularly in large populated cities and countries, such as Iran going through economic hardship.

The electroencephalography signal is well suited to calculate brain connectivity due to its high temporal resolution. When the purpose is to compute connectivity from multi-trial electroencephalography (EEG) data, confusion arises about how these trials involved in calculating the connectivity. The purpose of this paper is to study this confusing issue using simulated and experimental data. 

To this end, Granger causality-based connectivity measures were considered. Using simulations, two signals were generated with known AR (auto-regressive) coefficients and then simple multivariate autoregressive (MVAR) models based on different numbers of trials were extracted. For accurate estimation of the MVAR model, the data samples should be sufficient. Two Granger causality-based connectivity, granger causality (GC) and Partial directed coherence (PDC) were estimated.

Estimating connectivity corresponding to small trial numbers (5 and 10 trials) resulted in an average value of connectivity that is significantly higher and also more variable over different estimates. By increasing the number of trials, the MVAR model has fitted more appropriately to the data and the connectivity values were converged. This procedure was implemented on real EEG data. The obtained results agreed well with the findings of simulated data.

The results showed that the brain connectivity should calculate for each trial, and then average the connectivity values on all trials. Also, the larger the trial numbers, the MVAR model has fitted more appropriately to the data, and connectivity estimations are more reliable.

Frontoparietal (FPN) and cingulo-opercular network (CON) control cognitive functions needed in deductive and inductive reasoning via different functional frameworks. The FPN is a fast intuitive system while the CON is slow and analytical. The default-interventionist model presents a serial view of the interaction between intuitive and analytic cognitive systems. This study aims to examine the activity pattern of the FPN and CON from the perspective of the default-interventionist model via reasoning. 

We employed functional magnetic resonance imaging (fMRI) to investigate cingulo-opercular and frontoparietal network activities in 24 healthy university students during Raven and Wason reasoning tasks. Due to the different operation times of the CON and FPN, the reaction time was assessed as a behavioral factor.

During Raven’s advanced progressive matrices (RAPM) test, both the CON and FPN were activated. Also, with the increase in the difficulty level of the Raven test, a linear increase in response time was observed. In contrast, during the Wason’s selection task (WST) test, only the activity of FPN was observed.

The results of the study support the hypothesis that the default-interventionist model of dual-process theory provides an accurate explanation of the cognitive mechanisms involved in reasoning. Thus, the response method (intuitive/analytical) determines which cognitive skills and brain regions are involved in responding.

Memory is probably one of the most complex human cognitive functions, and in many years, thousands of studies have helped us better recognize this brain function. Professor Kandel and his colleagues have written one of the reference textbooks in neuroscience, which has also elaborated on the memory function. In this book, I encountered several ambiguities while explaining the memory system. Here, I share those points, either to find an answer to them or to let them be a suggestion for our future works. Professor Kandel has spent most of his meritorious lifetime studying the memory system; however, the brain is extremely complex, and as a result, we still have many years to comprehensively understand the neural mechanisms of brain functions.