فصلنامه علوم اعصاب شفای خاتم
سال دوم شماره 2 (پیاپی 6، بهار 1393)

Traumatic brain injuries may cause some neurological deficits¡ such as altered level of consciousness or coma¡ sensory-motor dysfunction¡ and seizure attacks. The neuroprotective effect of progesterone and erythropoietin has been shown in different types of brain injuries and cerebral ischemia. This study aims to evaluate the probable additional neuroprotective effects of progesterone and erythropoietin after brain injury.
The effects of progesterone¡ erythropoietin or the combination of these substances were investigated in 54 male Wistar rats suffering from traumatic brain injury. The effects of drugs were investigated using Modified Neurological Severity Scores as well as counting the number of dark neurons (injured cells) in the hippocampal CA1 and CA3 areas.
Our data revealed that the scale of neurological deficits increased by co-application of progesterone and erythropoietin in brain-injured rats. Assessment of dark neurons did not show a significant decrease in the number of dark neurons after combined treatment compared to control groups.
Our study showed that the combination therapy did not exhibit any synergistic effect and may worsen the outcome of traumatic brain injury.

Apoptosis plays a crucial role in normal development of central nervous system. In fact, disregulation of apoptosis is the major pathophysiological mechanism of many diseases, such as Alzheimer's disease. The aim of this survey was to study the role of apoptosis in neuronal injury during Alzheimer's disease.
The experiments were carried out in adult (6-7 months old) male Wistar rats (230-270 g) in 2 groups of sham and streptozocin (STZ). Animals in sham and STZ groups received normal saline and STZ intracerebroventricular (ICV) injections for two days, respectively. To assess neuronal apoptosis, 18, 45 and 90 days after STZ injection, TUNEL test was performed.
The result showed that apoptosis in hippocampal CA1 and CA3 areas were significantly increased in rats treated with STZ after 90 days. Also, there was a significant increase in the mean number of apoptotic cells in rats treated with STZ after 90 days compared to their age-matched sham group in the hippocampal CA1 and CA3 area.
ICV-STZ injection in rats was resulted in significant neuronal apoptosis in the hippocampus.

Tertiary (3D) structure determination using X-ray diffraction crystallography is a time consuming method, needs special facilities and expert operators. 3D structure determination by bioinformatics software is worth in experimental research, especially for drug discovery purposes and evolutionary relationships. Using computational biology software and databases, we have determined probable 3D structure of human voltage-gated sodium ion channels (VGSCs) and their developmental associations.
Amino acid sequences of VGSCs were obtained from Uniprot and used to predict their 3D structure using SWISS-MODEL server and by its definitive algorithm for protein basic local alignment search tool (BLAST)-(followed by visualization using Molegro Virtual Viewer software). Phylogenic tree was plotted using Mega 5 application for VGSCs sequences. VGSCs interactions were determined by String-db server.
According to the Neuron data-base, there are 9 types of human VGSCs named SCN1A-5A and SCN8A-11A. SWISS-MODEL software was just only able to predict some domains of VGSCs with high identity percentages. The identity percentages were variable for each VGSC and varied from 16.57% (SCN4A) to 100% (SCN2A, SCN5A). Blast results and drawing phylogenetic trees practice showed that animals, such as chimpanzee, gibbon, and gorilla have the most similar protein sequences.
In most cases, modeling using SWISS-MODEL is not enough decisive for prediction of protein 3D structure. Thus, we propose that researchers use mentioned animals for experiments of VGSCs, characterized structures for bioinformatics and drug designing surveys. In this case, the results of animal trials could be generalized to human more precisely.

The origin of 16% to 30% of low back pain is sacroiliac joint. It is difficult to distinguish the sacroiliac joint pain from other types of low back pain using history and physical examination. Radiological imaging has little role in diagnosis of the sacroiliac joint pain and diagnostic blocks are the gold standard in these patients. The main objective of this study is to evaluate the accuracy and safety of diagnostic sacroiliac joint block (DSJB) under sonographic guidance.
This analytic cross sectional study was conducted on 65 patients. DSJB under sonographic guidance was done for all patients with 1 ml radiographic contrast material and 1ml local anesthetic (2% lidocaine). In order to confirm intra-articular injection by sonographic guidance, fluoroscopic spot images were considered. The side effect and positive predictive value of physical provocative tests of sacroiliac joint were evaluated.
Of 65 diagnostic blocks, after fluoroscopic confirmation, 62 injections were intra-articular and only 3 were peri-articular. There was a significant statistical correlation between procedure time and patient's body mass index. 3 and 4 to 6 positive provocative tests of sacroiliac joint resulted in a positive predictive value of 83.3% and 93.3%, respectively. The procedure had no side effect and complication.
Based on the obtained results, diagnostic block of sacroiliac joint under sonographic guidance has reasonable accuracy without side effects. If performed by experienced clinicians in nerve block under sonographic guidance, it can be valuable alternative method for other guidance modalities in diagnosis of patient with sacroiliac joint pain.

Spinal cord injury (SCI) is a serious disabling condition associated with paralysis. Owing to suitable effects of hydrogels compared to preformed scaffolds, in this study a hydrogel based biomaterial, Matrigel, was applied. Matrigel is a termogel that forms nanofibers and hydrogel above 20°C. It contains laminin, nidogen and some growth factors that induce neural differentiation.
A moderate spinal cord contusion was performed in adult rats and 10 days after injury, matrigel was implanted. Then, they follow up via Basso, Beattie, Bresnahan test for 42 days. Cresyl violet staining was performed as a histopatological analysis.
Our data indicated less inflammation and dark cells in Matrigel group compared to control group. Locomotor test showed significant improvement of motor recovery in Matrigel group.
Our results suggest that Matrigel via some growth factors and adhesive molecules may have beneficial effects on functional recovery in SCI.

Despite major progress in pharmacological and surgical approaches, spinal cord injury remains a complex medical challenge. Cell replacement therapy is one of the new approaches for spinal cord injury treatment. In this study, bioactive substance TNT (a new supplement) was utilized for induction of bone marrow stromal cells (BMSCs) into neural stem cells (NSCs).
The BMSCs were extracted and cultured from the femurs and tibias of adult female wistar rats. After 3 or 4 passages, these cells were preinduced into neurospheres by TNT and neural induction supplement. Then neurospheres were induced into NSCs with B27 and TNT. The NSCs were evaluated with nestin, NF68 and SOX2.
The outcomes indicated that BMSCs were immunoreactive to CD106 (95.7 ± 0.76), OCT4 (96.2 ± 1.3) and CD45 (0.4 ± 1.2). The optimal dose and time for application of TNT were 1 M and 6 days, respectively. Differentiated cells were able to express nestin and NF68.
TNT as a non-toxic substance may be a good alternative for cell induction into NSCs for treatment of neurodegenerative disorders.

The ability to induce pluripotency in somatic cells by reprogramming factors offers new opportunities for drug discovery and cell therapy. Induced pluripotent stem cells have the potential to differentiate to various cell types, such as neural and glial cells. Astrocytes, the major glial cells of the central nervous system, play an important role in the function of the brain by regulating of extracellular ions and neurotransmitters, feeding and protection of neurons as well as modulating the activity of microglia. Microglia over-activation can be resulted in brain inflammation with subsequent susceptibility to epileptic seizures. Hypothesis: For many years, embryonic Stem cell transplantation has been examined to prevent seizure attacks in epilepsy. These studies have indicated that adult cells from patient have the ability to be transformed to embryonic stage and convert to a pluripotent stem cell by using some Transcription factors (such as Oct4, Sox2, Nanog, Rex1, Klf, c-Myc and LIN28). Accordingly, fibroblasts from an epileptic have also been reprogrammed to embryonic stage. The resulting iPS cells are isogenic to patient and are able to transform to neurons or glia in a suitable culture condition. Previous studies on ES cell therapy have focused more on neurons than astrocytes. Astrocytes, by secretion of glial cell-derived neurotrophic factor, not only regulate the different microglial activities, such as proliferation, migration and cell adhesion, but can also reduce destructive effects of microglia.
In this hypothesis, we suggest a reprogramming system for generating functional astrocyte from human pluripotent stem cell in the presence of neural growth factors. We hypothesize that these cells might reduce neuroinflammation induced by microglia and subsequent susceptibility to seizure. The reprogrammed cells could be used in cell replacement therapy of epilepsy.

Many internal medicine conditions may be presented to pain centers and an interdisciplinary and holistic approach is necessary for optimal management.
Case Description: A 46 year old man presented to the interdisciplinary pain clinic at Shefa Neuroscience Research Center complaining of periodic weakness, pain and tenderness in proximal lower extremities, anxiety, irritability and weight loss since 3 months ago. On examination and laboratory results, hyperthyroidism and severe hypokalemia were evident. On echocardiography, ejection fraction was 25%. He was admitted in coronary care unit for cardiac monitoring and received propranolol and methimazole.
After stabilizing the heart rate and correction of potassium level, paralysis was completely subsided and ejection fraction increased to 55%. He was discharged from the hospital in good situation.
Hyperthyroid hypokalemic periodic paralysis is a rare but well-known condition with episodes of muscular weakness or paralysis. It can be diagnosed by good history taking, physical examination, and laboratory evaluation. Appropriate therapy is necessary for treatment and prevention of paralytic episodes. Although the prognosis is usually good, in case of misdiagnosis and maltreatment this condition may be fatal.

Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system, plays a pivotal role in synchronization of local neural networks and coupling of brain regions functions. GABA is synthesized in the brain by a metabolic pathway known as ‘GABA shunt’ as it does not cross the blood-brain barrier. There are three types of GABA receptors named GABAA, GABAB and GABAC, which in turn are divided into two classes of ionotropic and metabotropic receptors. Ionotropic receptors of GABA including GABAA and GABAC receptors are ligand-gated ion channels, permit influx of chloride ion into neurons after activation, hyperpolarize membrane potential, and subsequently inhibit firing of new action potentials. GABAA receptors are heteropentameres of eight subunits including α, β, γ, δ, ε, θ, π and ρ, which some subunits have more than one isoform. Expression of α1, β2, γ2 subunits of the GABAA receptors in the brain is dominant. GABAC receptors only consist of ρ subunits. GABAB metabotropic receptors belong to G-protein coupled receptors, which via second messengers abolish calcium influx, increase potassium efflux, and decrease cAMP level in neurons. GABAB receptors are heterodimers of GABAB1 and GABAB2 subunits. Changes in expression of GABA receptors in different brain regions may cause some neuropsychological disorders, including schizophrenia, epilepsy, anxiety, sleep disorder and autism spectrum disorders.
With knowledge of diversities in subunit structure of GABA receptors in different brain areas, it is possible to treat neural disorders more effectively.

Memory is ability to acquisition, maintenance and retrieval of information, which is classified through different ways. Complex mechanisms play a role in learning and memory that ultimately leads to biochemical, morphological and physiological changes at the level of synaptic and neural networks. The basic mechanisms involved in the formation and stabilization of memory are synaptic facilitation, long term potentiation and long term depression.
Considering the importance of glutamate receptors (especially NMDA subtype), calcium homeostasis, balance between kinases and phosphatases, calcineurin, cellular adhesion molecules, extracellular matrix, glial cells, and different neurotransmitters in process of memory formation, this study evaluate the cellular and molecular pathways involved in learning and memory.