Letter to Editor

Concerns About Mesenchymal Stem Cell Therapy

Mahsa Haseli, Akbar Esmaeili

International Clinical Neuroscience Journal, Vol. 8 No. 1 (2021), 30 December 2020, Page 1-2

Dear Editor,

Multipotent mesenchymal stromal cells (MSCs), because of their potential for treating diseases, have gained considerable attention over the past 30 years for their immunosuppressive properties and tissue regeneration capabilities.1,2 This grew into an interest in the 1970s by Friedenstein and contemporaries after studying the bone m ar row.3 MSCs are an excellent candidate for cell therapy because of having intrinsic differentiation potentials into bone, cartilage and fat cells not found previously in other cells. They can also be isolated and expanded easily in vitro, and produce abundant useful growth factors and cytokines.2,4Mesenchymal stem cells have become the top used stem cell type for clinical application with encouraging results.5,6 Significant progress has been made in stem cell research in recent years. The main therapeutic effects of MSCs are now attributed to the stimulation of several innate repair processes in injured tissues in vivo by secreted factors as well as the immunomodulation response. Therefore, MSC therapy is expected to find clinical application in human diseases.6,7 However, there are some critical issues that need to be addressed before MSCs can be used for clinical therapy in humans which will help determine the efficiency of cells administered to the patients as a therapeutic approach, most important of which is immunosuppressive properties.8,9 MSCs can be affected by tumor support that may affect potential tumorigenesis after MSCs transplantation, including different donors and tissues, inconsistent protocols, varying dosages and differing transfusion patterns, and mechanisms that control the behavior of the MSCs at the target site.10,11 Because of their unique features, stem cells are undoubtedly a great hope for the treatment of many diseases. More research is developing on the potential long-term risks associated with MSC therapy. However, Additional studies would also be a major contribution to stem cell biology in general as well as their transplantation.

Review Article

Neurocognitive Manifestations of SARSCoV2: A Narrative Review of Mechanisms

Mahrooz Roozbeh, Mehrdad Roozbeh, Hossein Pakdaman, Seyed Ali Sobhanian, Amin Edalatkhah, Saeid Safari

International Clinical Neuroscience Journal, Vol. 8 No. 1 (2021), 30 December 2020, Page 3-9

Since the outbreak of COVID-19 that is caused by severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) in 2020 throughout the world, a lot of aspects of people’s lives are affected including
their psychological status. Follow-up assessment of survivors of this infection showed that they
had multiple psychological disorders including depression, panic attacks, obsessive compulsive
disorder, and post-traumatic stress disorder. It is estimated that more than one-third of patients with
COVID-19 experience neuropsychiatric symptoms, including headache, paresthesia, and disturbed
consciousness. Among patients affected by COVID-19, there are different mechanisms that can
cause cognitive dysfunction. COVID-19 can affect the central nervous system (CNS) directly by
invasion and indirectly by inducing hypoxia, inflammation, and delirium. The pandemic and fear
of infection can also cause anxiety which impairs the cognition as well. By assessing the patients’
cognition and knowing the higher probable cause of cognitive impairment, we can form a better
strategy to better treat the impairment. Cognitive behavioral therapy can be effective in reducing the
anxiety and cognitive rehabilitation therapy (CRT) can be used to lower the detrimental effects of
cognitive impairment caused by COVID-19.

Original / Research Article

Effectiveness of Autologous Schwann Cell and Bone Marrow-Derived Mesenchymal Stem Cell Transplantation for Individuals With Spinal Cord Injury in Promoting Sensory Recovery

Maryam Golmohammadi, Mohammadhosein Akhlaghpasand, Saeed Oraee-Yazdani, Alireza Zali

International Clinical Neuroscience Journal, Vol. 8 No. 1 (2021), 30 December 2020, Page 9-13

Background: In recent decades, improvement in sensory and motor function after spinal cord injury
(SCI) is a major treatment goal. Stem cell therapy has become a promising treatment strategy in the
regeneration of central nervous system injuries.
Methods: We assessed the effectiveness of autologous Schwann cell (SC) and bone marrow-derived
mesenchymal stem cell (MSC) for individuals with SCI in promoting sensory recovery. Five patients
with a mean ± SD age of 38.80 ± 5.84 years were enrolled in the study. The follow-up course was
12 months.
Results: We found sensory changes in two patients assessed by the American Spinal Injury
Association’s (ASIA’s) impairment scale. Systemic complications were not observed during the
course of the study.
Conclusion: There were no adverse finding after cell transplantation. Also we observed improvement
in sensory score in two patients. It seems that the use of this combination of cell therapy may be
effective; but large group studies with control group are required to clarify the effect of either cells.

Berberine Supplement and Resistance Training May Ameliorate Diazinon Induced Neural Toxicity in Rat Hippocampus Via the Activation of the TrkB and ERK Signaling Pathway

Elham Shakouri, Mohammad Ali Azarbayjani, Seyed Behnamedin Jameie, Maghsoud Peeri, Mona Farhadi

International Clinical Neuroscience Journal, Vol. 8 No. 1 (2021), 30 December 2020, Page 14-21

Background: Diazinon is an organophosphate pesticide that is broadly applied to control insects
which causes oxidative damages in hippocampus tissue. We aimed to examine whether resistance
training and berberine supplementation can protect the hippocampus against berberine-induced
neural toxicity.
Methods: Fifty-six male Wistar rats were assigned randomly into eight groups of seven including:
Control (Ctrl), Sham (normal saline), T1 (diazinon + berberine chloride (2 mg/kg) + resistance
training), T2 (diazinon + berberine chloride [15 mg/kg] + resistance training), T3 (diazinon), T4
(diazinon +resistance training), T5 (diazinon + berberine chloride [2 mg/kg]), and T6 (diazinon
+ berberine chloride [15 mg/kg]). In the experimental groups, diazinon was intraperitoneally
administered at a dose of 1.5 mg/kg. In the training groups, rats were trained every three days for six
weeks and 8-12 dynamic movements (repetitions) during each climb (six climbs for two sets). The
expression of hippocampus PI3K and CDK genes and TrkB and ERK protein levels were evaluated in
the brain of diazinon-treated rats.
Results: The protein expression of ERK and TrkB were increased following the treatment of diazinonintoxicated rats with berberine and resistance training (P=0.001). The administration of berberine
at a dose of 15 mg/kg in combination with resistance training significantly (P=0.001) decreased
the cell death rate in the hippocampus. Diazinon treatment caused extensive apoptosis in the
hippocampus region of the rats’ brain (P=0.001). The gene expression of PI3K and CDK was
significantly increased and the cell death rate significantly decreased (P=0.001) in the hippocampus
following the treatment of rats with berberine and resistance training.
Conclusion: Six weeks of resistance training in combination with berberine treatment significantly
reduced apoptosis in the hippocampus region of diazinon-intoxicated rats. It seems the
neuroprotection effects of berberine and resistance training are mediated by the stimulation of the
expression of enzymes responsible for the antioxidant defense within neuronal cells

Isolation of Cancer Stem Cells and Astrocytes from Human Glioblastoma: Morphological Characterization of Two Cells Types

Mansoureh Hashemi

International Clinical Neuroscience Journal, Vol. 8 No. 1 (2021), 30 December 2020, Page 22-25


 Background: Glioblastoma multiforme is the most aggressive astrocytoma in adults. Glioblastoma is a heterogenous tumor formed from various cells including astrocyte and cancer stem cells. Here, we explain the isolation, culture, morphology and specific markers of human glioblastoma astrocyte and stem cells.

Methods: We isolated astrocyte and cancer stem cells from human glioblastoma tissue. The obtained glioblastoma tissues were digested and cultured in DMEM12, B27 supplemented with basic fibroblast growth factor and epidermal growth factor . The morphology and specific markers were assessed in astrocyte and cancer stem cell of human glioblastoma through immunochemistry.

Results: Results indicated that there were two morphology types in cell culture including epithelioid morphology and fibroblastic morphology. The astrocyte confirmed via expression of the GFAP protein. Cancer stem cells were round and floating in the culture medium. Immunocytochemical staining indicated that nestin and SOX2 antigens were positively expressed in primary neurospheres.

Conclusion: The expression of glial and stem cell markers show that both cells are in the human glioblastoma.

Clinical and Pathological Features of Lipid Storage Myopathy; A Retrospective Study of a Large Group from Iran

Yalda Nilipour, Parveneh Karimzadeh, Shahriar Nafissi, Mohammad Mahdi Taghdiri, Hedyeh Saneifard, Marjan Shakiba, Yalda Rahbarfar

International Clinical Neuroscience Journal, Vol. 8 No. 1 (2021), 30 December 2020, Page 26-29

Background: Lipid storage myopathies (LSMs) are rare diseases. The phenotype and genotype of lipid metabolism disorders are heterogeneous and divided into two major groups. Constant or progressive proximal and axial muscle weakness associated with or without metabolic crisis, is often seen in patients with LSM such as primary carnitin deficiency (PCD) or multiple acyl-coenzyme a dehydrogenase deficiency disorder (MADD). On the other hand, rhabdomyolysis triggered by fasting, fever, or physical activity usually occurs in patients with disorders affecting intramitochondrial fatty acid transport and β-oxidation, such as carnitine palmitoyltransferase II deficiency (CPT2), mitochondrial trifunctional protein deficiency and very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD).

Methods: In this cross-sectional study, we summarized the clinical profiles and muscle histology of 64 Iranian patients diagnosed with LSM by muscle biopsy. These patients were selected from 3000 patients referred for muscle biopsy to Toos and Mofid children’s hospitals during 2010 to 2016. Their affected siblings were also added to the study.

Result: In our study 45.3% of the patients were men and 54.7% were women. Mean age of the patients was 27.05 years (SD: 14.26) and the mean age of onset of symptoms in these patients was 20.94 (SD: 14.25) years.  Most patients (70.3%) had proximal weakness and no bulbar involvement. Only 9.3% of the patients had a positive family history.

Conclusion: LSMs are not incommon in Iran and their phenotype can mimic inflammatory myopathy or limb girdle muscular dystrophy. Overall the demographic and clinical features of LSMs in Iranian patients were similar to prior reports.

Introduction: We aimed to compare and determine the effectiveness of three methods of attention training based on Fletcher's program, Delacato's neuropsychological treatment, and computerized cognitive rehabilitation, on executive functions of children with special learning disability.

Methods: This was a four-group pretest-posttest design with a control group (three experimental groups and one control group) quasi-experimental study. The population included all students aged 7 to 12 years with learning disorders referred to the Learning Disorders Treatment Centers in Tehran during 2019. First, 40 students were selected from these centers by convenience sampling. This number was then randomly divided into four groups of attention training based on Fletcher's program, Delacato's neuropsychological treatment, computerized cognitive rehabilitation, and one group as a control group (N=10). Three methods of attention training based on Fletcher's program (12 sessions of 45 minutes), Delacato's neuropsychological method (12 sessions of 50 minutes), computerized cognitive rehabilitation (10 sessions of 30 minutes individually), were separately trained to the three experimental groups. Gerard and colleagues’ (2000) Behavioral Rating Inventory of Executive Functions (parent form) was used to collect data.

Results: The results of the study revealed that the three methods were effective on executive functions in children with a special learning disability (P<0.05). Based on the results of the post hoc test, the scores of both attention training groups based on Fletcher's program and computerized cognitive rehabilitation method were significantly different from the control group (P<0.0001). This indicates that both interventions had an effect on increasing the executive function of children with special learning disability, but there was no significant difference between the three experimental groups (P>0.05).

Conclusion: Given that computers are available in almost all schools, such programs can be considered as part of the curriculum for students with learning disabilities. Accordingly, through Fletcher’s attention-based training method and computerized cognitive rehabilitation improved the performance of this group and prevented the creation of a defective process of failure in these students by improving their executive functions.

Effectiveness of Group Therapy Based on Acceptance and Commitment on the Severity of Fatigue and Depression with the Moderating role of Alexithymia in Multiple Sclerosis Patients

Tahereh Haji Seyed Javadi, Maryam Aghel Masjedi, Elnaz Hamzehloo, Mir Javad Chehraghi, Leila Razavi, Soheila Rahmani, Somayeh Nejati

International Clinical Neuroscience Journal, Vol. 8 No. 1 (2021), 30 December 2020, Page 37-43

Objective: Alexithymia is a symptom that most psychosomatic patients experience and can affect their performance, psychological state, and the severity of their physical symptoms. Therefore, the present study was conducted to determine the effectiveness of group therapy based on acceptance and commitment on the severity of fatigue and depression with the moderating role of alexithymia in MS patients in Tehran.

Methodology: In this research, a semi-experimental design was used with pre-test, post-test, and three months of follow-up. Using convenience sampling, 40 patients with MS were randomly assigned to two experimental and control groups. Before and after the intervention and three months later in the follow-up phase, all of the subjects responded to fatigue severity, depression, and alexithymia questionnaires. The intervention consisted of 10 sessions of 90-minutes group therapy based on acceptance and commitment, which was provided only to the experimental group.

Findings: Analysis of covariance indicated a significant difference between the mean scores of fatigue severity, depression, and alexithymia in the experimental and control groups in post-test and follow-up stages.

Conclusion: The findings of this study indicated the effectiveness of group therapy based on acceptance and commitment on reducing the severity of fatigue and depression with the moderating role of alexithymia in MS patients.



Case Series

Motor Task Processing After Constraint- Induced Movement Therapy in Children With Cerebral Palsy: A Case Series

Dr. Karen P.Y. Liu, Dr. Michael Kuo, Dr. Kin-hung Ting

International Clinical Neuroscience Journal, Vol. 8 No. 1 (2021), 30 December 2020, Page 44-47

Constraint-induced movement therapy (CIMT) has shown positive results in children with hemiplegic cerebral palsy (CP). However, studies on neural basis of such functional gains are limited. This study reports the event-related potential (ERP) changes in two children with hemiplegic CP after receiving CIMT for three weeks. Both cases were nine years old, had a diagnosis of left hemiplegic CP, had normal intelligence, and were able to extend the wrist at least 20° and the metacarpophalangeal joint at least 10° from full flexion. Before and after the three-week intervention, the children participated in ERP sessions with a choice reaction task to capture the changes in neural mechanism after intervention. Both children exhibited improvement in reaction time (RT) in both hand tasks after the intervention. The improvement was larger in the affected hand than the unaffected hand. Improved accuracy rate (AC) and shortened P300 latencies in the affected hand were also demonstrated in both cases. Topographical maps showed that in centro-parietal regions, patterns shifted from central and left-lateralized to more central and right-lateralized. CMIT was a useful method in improving upper limb function in our cases.

Case Report

A Rare Case of Type II Odontoid Fracture With Bilateral Vertebral Arteries Occlusion Without Neurological Deficits

Morteza Sanei Taheri, Hamidreza Haghighatkhah, Arash Azhideh, Mehran Arab Ahmadi

International Clinical Neuroscience Journal, Vol. 8 No. 1 (2021), 30 December 2020, Page 48-50

Cervical spine fractures are common fractures due to spine trauma. Odontoid fracture is responsible for 20% of cervical spine fractures. Vertebral artery injuries (VAIs) had widely focused in this setting due to its occurrence with upper cervical fractures. In our case of study, a 42-year-old female presented in the hospital’s emergency department with a history of cervical spine injury without neurological deficits. In further investigations, cervical spine X-ray, magnetic resonance imaging (MRI), and angiography were done to evaluate the possible injuries to the bone, spinal cord, and vascular structures surrounding the spine that eventuated in the accidental diagnosis of bilateral vertebral artery occlusion. This case of the study demonstrated the importance of diagnostic investigations that can evaluate in an emergency department and bilateral vertebral artery occlusion without neurological symptoms due to collateral arteries establishment.