Basic and Clinical Neuroscience
Volume:13 Issue: 5, Sep-Oct 2022

Electrical impedance tomography (EIT) is a non-invasive technique utilized in various medical applications, including brain imaging and other neurological diseases. Recognizing the physiological and anatomical characteristics of organs based on their electrical properties is one of the main applications of EIT, as each variety of tissue structure has its own electrical characteristics. The high potential of brain EIT is established in real-time supervision and early recognition of cerebral brain infarction, hemorrhage, and other diseases. In this paper, we review the studies on the neurological applications of EIT.

EIT calculates the internal electrical conductivity distribution of an organ by measuring its surface impedance. A series of electrodes are placed on the surface of the target tissue, and small alternating currents are injected. The related voltages are then observed and analyzed. The electrical permittivity and conductivity distributions inside the tissue are reconstructed by measuring the electrode voltages.

The electrical characteristic of biological tissues is remarkably dependent on their structures. Some tissues are better electrical conductors than the others since they have more ions that can carry the electrical charges. This difference is attributed to changes in cellular water content, membrane properties, and destruction of tight junctions within cell membranes. 

EIT is an extremely practical device for brain imaging, capturing fast electrical activities in the brain, imaging epileptic seizures, detecting intracranial bleeding, detecting cerebral edema, and diagnosing stroke.

The present systematic review and meta-analysis aims to conduct a comprehensive and complete search of electronic resources to investigate the role of administrating Chondroitinase ABC (ChABC) in improving complications following Spinal Cord Injuries (SCI).

MEDLINE, Embase, Scopus, and Web of Sciences databases were searched until the end of 2019. Two independent reviewers assessed the studies conducted on rats and mice and summarized the data. Using the STATA 14.0 software, the findings were reported as pooled standardized mean differences (SMD) with 95% confidence intervals (CI). 

A total of 34 preclinical studies were included. ChABC administration improves locomotion recovery after SCI (SMD=0.90; 95% CI: 0.61 to 1.20; P<0.001). The subgroup analysis showed that the differences in the SCI model (P=0.732), the severity of the injury (P=0.821), the number of ChABC administrations (P=0.092), the blinding status (P=0.294), the use of different locomotor score (P=0.567), and the follow-up duration (P=0.750) have no effect on the efficacy of ChABC treatment.

The findings of the present study showed that prescribing ChABC has a moderate effect in improving locomotion after SCI in mice and rats. However, this moderate effect introduces ChABC as adjuvant therapy and not as primary therapy.

The induction of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) toward dopaminergic neurons is a major challenge in tissue engineering and experimental and clinical treatments of various neurodegenerative diseases, including Parkinson disease. This study aims to differentiate HUC-MSCs into dopaminergic neuron-like cells.

Following the isolation and characterization of HUC-MSCs, they were transferred to Matrigel-coated plates and incubated with a cocktail of dopaminergic neuronal differentiation factors. The capacity of differentiation into dopaminergic neuron-like cells in 2-dimensional culture and on Matrigel was assessed by real-time polymerase chain reaction, immunocytochemistry, and high-performance liquid chromatography.

Our results showed that dopaminergic neuronal markers’ transcript and protein levels were significantly increased on the Matrigel differentiated cells compared to 2D culture plates.

Overall, the results of this study suggest that HUC-MSCs can successfully differentiate toward dopaminergic neuron-like cells on Matrigel, having great potential for the treatment of dopaminergic neuron-related diseases.

Parkinson disease (PD) results from the destruction of dopaminergic neurons in the brain. This study aimed to investigate the protective effects of natural antioxidants such as caffeic acid phenethyl ester (CAPE) to maintain these neurons.

CAPE is one of the main ingredients of propolis. Intranasal administration of 1-methyl-4-phenyl-2;3;4;6-tetrahydropyridine (MPTP) was used to generate a PD model in rats. A total of 2×bone marrow stem cells (BMSCs) were injected from the tail vein. Behavioral tests, immunohistochemistry, DiI, cresyl fast violet, and TUNEL staining were used to evaluate the rats 2 weeks after treatment.

In all treatment groups with stem cells, the DiI staining method revealed that the cells migrated to the substantia nigra pars compacta after injection. Treatment with CAPE significantly protects dopaminergic neurons from MPTP. The highest number of tyrosine hydroxylase (TH) positive neurons was seen in the pre-CAPE+PD+stem cell (administration of CAPE, then the creation of PD, finally injection of stem cells) group. The number of TH+cells in all groups that received CAPE was significant compared to groups that received the stem cells only (P<0.001). Intranasal administration of MPTP significantly increases the number of apoptotic cells. The lowest number of apoptotic cells was in the CAPE+PD+stem cell group. 

The results showed that the use of CAPE and stem cells in Parkinson rats caused a significant reduction in the apoptotic cells.

The functions of the endoplasmic reticulum (ER) are important, particularly in the proteins’ synthesis, folding, modification, and transport. Based on traditional medicine and our previous studies on Zanthoxylum alatum in lipopolysaccharide-induced depressive behavior and scopolamine-induced impaired memory, the present study explored the role of hydroalcoholic extract of Z. alatum (ZAHA) seeds in reducing the ER stress in mice.

The mice were restrained for 28 days in polystyrene tubes. ZAHA (100 and 200 mg/kg, PO) and imipramine (10 mg/kg, IP) were administered daily, 45 min before restraint from day 22 to 28. The mice were assessed by the forced swim test. Also, the antioxidant enzyme levels of Superoxide Dismutase (SOD), reduced glutathione (GSH), and lipid peroxidation (LPO) were measured in the hippocampus of mice. The expression of 78 kDa glucose-regulated protein (GRP78), 94 kDa Glucose-Regulated Protein (GRP94), and C/EBPhomologous protein (CHOP) genes was assessed by real-time PCR to explore the molecular mechanism.

ZAHA (100 and 200 mg/kg, PO, and imipramine, IP) counteracted the stress by significantly reducing the immobility time in the force swimming test, receding oxidative stress and lipid peroxidation. The antioxidant enzyme (SOD and GSH) levels were elevated in the restraint stress group. Down-regulation of genes (GRP78, GRP94, and CHOP) compared to the chronic restraint stress group indicated stress modulating properties of the seeds in ER stress. Hesperidin, magnoflorine, melicopine, and sesamin, isolated from the active extract, were hypothesized to exert the activity.

It can be concluded that Z. alatum reverted chronic restraint stress through its antioxidant properties and down-regulation of genes involved in ER stress.

Memantine (MEM) is a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist clinically used for the treatment of Alzheimer disease (AD) in mild to severe conditions. The present study was conducted to investigate the effects of memantine on the spontaneous firing frequency of CA1 pyramidal neurons in rats caused by an electrical lesion of Nucleus Basalis Magnocellularis (NBM). Then, this model of AD rats was compared with the intact adult male rats.

In this study, adult male rats were divided into two groups. Group I (lesion of NBM, n=53) includes the following subgroups: lesion+saline, sham+saline, lesion+MEM 5 mg/kg, lesion+MEM 10 mg/kg, and lesion+MEM 20mg/kg. Group II (intact, n=48) includes the following subgroups: intact+saline, intact+MEM 3mg/kg, intact+MEM 5mg/kg, and intact+MEM 10mg/kg. Extracellular single-unit recording (15 min baseline+105 min after MEM or saline) was performed under urethane-anesthetized rats. 

The results showed that the mean frequency of CA1 pyramidal neurons after saline in the lesion+saline (P<0.001) group significantly decreases compared with the intact+saline and sham+saline groups. In addition, after saline and memantine, the mean frequency of CA1 pyramidal neurons in the lesion+MEM 10 mg/kg (P<0.01) and lesion+MEM 20 mg/kg (P<0.001) groups significantly increased compared with the lesion+saline group. Also, the mean frequencies of CA1 pyramidal neurons in the intact+MEM 10 mg/kg (P<0.001) group significantly decreased compared with the intact+saline group. 

Results showed that memantine increases the electrical activity of CA1 pyramidal neurons in a rat model of AD. Furthermore, in the intact adult male rats, the low-dose memantine, contrary to high dose, does not decrease the electrical activity of CA1 pyramidal neurons.

Alzheimer disease (AD) is the most common form of dementia worldwide. The modalities to diagnose AD are generally expensive and limited. Both the central nervous system (CNS) and the retina are derived from the cranial neural crest; therefore, changes in retinal layers may reflect changes in the CNS tissue. Optical coherence tomography (OCT) machine can show delicate retinal layers and is widely used for retinal disorders. This study aims to find a new biomarker to help clinicians diagnose AD via retinal OCT examination. 

After considering the inclusion and exclusion criteria, 25 patients with mild and moderate AD and 25 healthy subjects were enrolled in the study. OCT was done for all eyes. The central macular thickness (CMT) and the ganglion cell complex (GCC) thickness were calculated. The groups were compared using the SPSS software, v. 22.

Both GCC thickness and CMT were significantly decreased in patients with AD when compared to healthy age- and sex-matched individuals.

Retinal changes, specifically CMT and GCC thickness, may reflect the AD process in the brain. OCT can be considered a non-invasive and inexpensive method to help diagnose AD.

Appropriate information about the ability of patients with Parkinson disease (PD) to perform cognitive instrumental activities of daily living (IADL) is necessary. The present study aimed to assess the psychometric properties of the Persian version of the Penn Parkinson daily activities questionnaire-15 (PDAQ-15).

A total of 165 knowledgeable informants of PD patients completed the PDAQ-15. The clinical dementia rating scale, Hoehn and Yahr staging, hospital anxiety and depression scale (HADS), and Lawton IADL scale were used in the study. Internal consistency and test-retest reliability were evaluated by the Cronbach α coefficient and intraclass correlation coefficient (ICC), respectively. To examine the dimensionality of the questionnaire, exploratory factor analysis was used. The construct validity was assessed using the Spearman rank correlation test. To assess the discriminative validity, PDAQ-15 scores were compared across cognitive stages.

The PDAQ-15 showed strong internal consistency (the Cronbach α=0.99) and test-retest reliability (ICC= 0.99). Only one dimension was identified for the PDAQ-15 in the factor analysis. There was a strong correlation between PDAQ-15 with the depression domain of the HADS scale and the Lawton IADL scale (rs=|0.71–0.95|). The correlation of PDAQ-15 with the anxiety domain of the HADS scale was moderate (rs=0.66). Discriminative validity analysis showed that the PDAQ-15 has significant power to discriminate between PD patients across cognitive stages.

These results suggest that the PDAQ-15 is a valid and reliable PD-specific instrument and can be useful in clinical and research settings.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder in women that is associated with an increased risk of infertility. This study aims to evaluate the neurobehavioral and neurochemical changes along with the associated changes in the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) of the dehydroepiandrosterone (DHEA)-induced PCOS model rats.

A total of 12 female juvenile Wistar rats (30 to 50 g) about 22 to 44 days old were divided into 2 groups. The control group received sesame oil while the PCOS group received sesame oil plus DHEA. All treatment was done via daily subcutaneous injection for 21 days.

Subcutaneous DHEA-induced PCOS significantly depleted the line crossing and rearing frequency in the open field, along with the percentage of the time in the white box, line crossing, rearing, and peeping frequency in the black and white box, and the percentage of alternation in the Y-maze. PCOS significantly increased the immobility time, freezing period, and the percentage of time in the dark area in the forced swim test, open field test, and black and white box, respectively. The level of luteinizing hormone, follicle-stimulating hormone, malondialdehyde (MDA), reactive oxygen species (ROS), and interleukin-6 (IL-6) increased significantly, while norepinephrine depleted significantly with an obvious decrease in the brain-derived neurotrophic factor level in the PCOS model rats. PCOS rats exhibited cystic follicles in the ovaries and necrotic or degenerative like features in the hippocampal pyramidal cells.

DHEA-induced PCOS results in anxiety and depressive behavior with structural alteration in rats, possibly through the elevation of MDA, ROS, and IL-6 levels, which also attributes to impaired emotional and executive functions in the mPFC and ACC.

Maintenance of neurogenesis depends on the function of some histone-modifying enzymes; including Enhancer of zeste homolog 2 (EZH2) and histone acetyltransferases (P300). The mechanism of epigenetic regulation and gene expression underlying the transition of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) into MNs has not been fully clarified. 

Two morphogens; sonic hedgehog (Shh: 100 ng/mL) and retinoic acid (RA: 0.01 mM) were involved in the specification of hUCB-MSCs into MNs after MSC characterization using Flow cytometry. Real time-quantitative PCR and immunocytochemistry were performed to find the expression of the genes at the level of mRNA and protein. 

The expression of MN-related markers was confirmed at the level of mRNA and protein by induction of differentiation. The results were confirmed by immunocytochemistry and showed those mean cell percentages of 55.33%±15.885% and 49.67%±13.796% could express Islet-1 and ChAT, respectively. The gene expression level of Islet-1 and ChAT was significantly increased in the first and second week of exposure, respectively. After two weeks, the expression level of P300 and EZH-2 genes increased remarkably. No significant expression of Mnx-1 was detected when compared to the control sample.

MN-related markers, Islet-1 and ChAT, were detected in differentiated cells of hUCB-MSCs, supporting the potency of cord blood cells in the regeneration of MN-related disorders. Assessing these epigenetic regulatory genes at the protein level can be suggested to confirm their functional epigenetic modifying effects during motor neuron differentiation.

Several neuropsychiatric disorders, such as addiction, have indicated variations in the levels of neurotrophic factors. As an extremely addictive stimulant, methamphetamine (METH) is associated with rising levels of abuse worldwide. We have recently demonstrated that repeated intracerebroventricular (ICV) of cannabidiol (CBD), the most important non-psychotomimetic compound, can lead to diminished impairing memory and hippocampal damage caused by chronic exposure to METH (CEM) in rats over the abstinence period. Furthermore, the results indicated a possible contribution of the neurotrophin signaling pathway (NSP) in regulating neurogenesis and survival. This study intends to evaluate whether these effects remained as measured in molecular pathways after the abstinence period.

The animals were given 2mg/kg METH twice a day for 10 days. Then, we adopted real-time polymerase chain reaction (PCR) throughout the 10-day abstinence period to assess the CBD’s effect (10 and 50μg/5μL) on the levels of the mRNA expression of the NSP.

The findings suggested that CEM, when compared to the control group in the hippocampus, downregulated mRNA expression of NSP. Moreover, a dosage of 50 μg/5μL CBD may possibly enhance the mRNA expression level of BDNF/TrkB and NGF/TrkA in the hippocampus. Besides, the expression of RAF-1 mRNA level could be reversed significantly by both doses of CBD.

According to our results, CBD may partly bring about neuroprotective effects by modulating the NSP. These findings set forth solid evidence demonstrating that CBD is a protective factor attributed to neuropsychiatric disorders, such as METH addiction.

Natural rewards are essential for survival. However, drug-seeking behaviors can be maladaptive and endanger survival. The present study was conducted to enhance our understanding of how animals respond to food and morphine as natural and drug rewards, respectively, in a conditioned place preference (CPP) paradigm.

We designed a protocol to induce food CPP and compare it as a natural reward with morphine CPP in rats. The protocol for reward induction in both groups (foods and morphine) consisted of three phases: pre-test, conditioning, and post-test. In morphine groups, we injected morphine as a reward (5 mg/kg, SC). To induce natural reward, we used two different protocols. In the first one, the rats were deprived of food for 24 h. In the other method, the rats were restricted to food for 14 days. During the conditioning period, the animals received daily chow, biscuits, or popcorn as a reward inducer.

Results revealed that CPP was not induced in food-deprived rats. A combination of food restriction (as a facilitator) and a biscuit or popcorn-induced reward using CPP. In contrast, food deprivation did not facilitate food CPP in response to regular food. Interestingly the CPP score of the group which received biscuits during a 7-day conditioning period was more than that of the morphine group.

In conclusion, food restriction could be a better protocol than food deprivation to facilitate food reward.