Acta neurobiologiae experimentalis (ACTA NEUROBIOL EXP)
Description
Acta Neurobiologiae Experimentalis (quarterly) publishes the results of original brain research in English.
- Impact factor2.11
- WebsiteActa Neurobiologiae Experimentalis (Warsaw) website
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Other titlesActa neurobiologiae experimentalis (Online)
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ISSN1689-0035
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OCLC50995560
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Material typeDocument, Periodical, Internet resource
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Document typeInternet Resource, Computer File, Journal / Magazine / Newspaper
Publications in this journal
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Article: The number decision task: Investigation of the representation of multi-digit numbers
Acta neurobiologiae experimentalis 04/2013; -
Article: Epigenetic and molecular signature of human umbilical cord blood-derived neural stem cell (HUCB-NSC) neuronal differentiation.
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ABSTRACT: In the context of cell therapy, the epigenetic status of core stemness transcription factor (STF) genes regulating the cell proliferation/differentiation program is of primary interest. Our results confirmed that in vitro differentiation of the umbilicalcord-blood-derived-neural-stem-cells (HUCB-NSC) coincides with the progressive down-regulation of Oct3/4 and Nanog gene expression. Consistently and in parallel with the repression of gene transcription, a substantial increase in the mosaic cytosine methylation CpG dinucleotide was observed in the promoter regions of these STF genes. However none of the histone-H3 post-translational-modifications (PTM) known to be associated with transcriptionally active genes (H3Ac and H3K4me3) or repressed genes (H3K9me3 and H3K27me3) seemed to vary in relation to the progression of cell differentiation and down-regulation of STF genes. This indicates an uncoupling between STF gene expression and above mentioned histone PTMs. In contrast, the overall methylation of nuclear chromatin at repressive histone H3K9me3 was significantly higher than H3K4 trimetylation in expanding HUCB-NSC cultures and then increases through the progression of cell differentiation. These observations suggest different epigenetic programs of gene repression realized in the cell nuclei of differentiating HUCB-NSC cultures with uneven involvement of the repressive histone PTMs.Acta neurobiologiae experimentalis 01/2013; 73(1):143-56. -
Article: Oxygen-glucose deprivation promotes gliogenesis and microglia activation in organotypic hippocampal slice culture: Involvement of metalloproteinases.
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ABSTRACT: Organotypic hippocampal cultures are used as an alternative model for studying molecular mechanism(s) of neurogenesis after combined oxygen-glucose deprivation (OGD) mimicking ischemic conditions. The aim of the present work was to investigate the effect of OGD on stem/progenitor cells proliferation and/or differentiation in the hippocampus. Our attention was primarily focused on the relationship between neurogenesis-associated processes and activity of matrix metalloproteinases (MMPs). Cell proliferation was detected by using BrdU incorporation. Newly generated BrdU (+) cells were identified by labeling with specific cell markers. In order to check the activity and localization of MMPs we conducted in situ zymography in conjunction with immunohistochemistry. In our experimental conditions OGD-insult followed by 24 h of recovery caused the damage of neuronal cells in CA1. At 1 week cell death appears all over the hippocampus. We found that expected stimulation of endogenous neurogenesis fails as a source of compensation for the lost neurons in OGD-treated cultures. The modulation of culture microenvironment after ischemia favors the dominant proliferation of glial cells expressed by the enhancement of newly-generated oligodendrocyte progenitors. In addition, during our study we also detected some BrdU labeled nuclei encapsulated by GFAP positive processes. However, the majority of BrdU positive cells expressed microglial specific stain, particularly pronounced in CA1area. The OGD-promoted responses involved activation of metalloproteinases, which matches the progression of gliogenesis. On the other hand, the high activity of MMPs associated with microglial cells implicate their involvement in the mechanism participating in OGD-induced cell damage.Acta neurobiologiae experimentalis 01/2013; 73(1):130-42. -
Article: Different methods of immunosuppresion do not prolong the survival of human cord blood-derived neural stem cells transplanted into focal brain-injured immunocompetent rats.
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ABSTRACT: Cerebrovascular diseases are the leading cause of severe disability worldwide, with an enormous financial burden for society. There is growing evidence that stem cell-based therapy may positively influence recovery from stroke. Cord blood is an attractive source of ontogenetically young, yet safe, stem cells. Conceptually, preclinical studies in which donor cells were of human origin have been the most valuable, and thus, it is likely that these cells will be used in clinical trials. Unfortunately, immunological barriers impede discordant xenotransplantations. We have previously observed acute rejection of cord blood derived neural stem cells (HUCB-NSC) after transplantation to the brains of intact animals. Since it was reported recently that a brain lesion may actually improve the chances of graft survival, in this study, we used infarcted animals as graft recipients. In ongoing studies, we tested three immunosuppressive regimes: group I received cyclosporine A (CsA: 10 mg per kg i.p.); group II received a triple-drug therapy (CsA: 10 mg per kg i.p., azathioprine: 5 mg per kg i.p., and methylprednisolone: 1.5 mg per kg i.m.); group III included rats that were formerly desensitized with HUCB, group IV had not undergone immunosuppression. Animals were sacrificed at five time-points: 1, 3, 7, 14, and 21 days post-transplantation to evaluate graft survival and the time-course of immunological response. We observed a gradual decrease in the number of transplanted cells, with complete disappearance by day 14, surprisingly, with no difference among the experimental groups. The involvement of the innate immune system in the process of graft rejection dominated over an adaptive immunoresponse, with the highest activity on day 3, and subsequent fading of immune cell infiltration. In this work, we have shown that none of our immunosuppressive strategies proved adequate to prevent rejection of human stem cell grafts after transplantation into immunocompetent animals.Acta neurobiologiae experimentalis 01/2013; 73(1):88-101. -
Article: Object-based analysis of astroglial reaction and astrocyte subtype morphology after ischemic brain injury.
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ABSTRACT: The astrocytic response to ischemic brain injury is characterized by specific alterations of glial cell morphology and function. Various studies described both beneficial and detrimental aspects of activated astrocytes, suggesting the existence of different subtypes. We investigated this issue using a novel object-based approach to study characteristics of astrogliosis after stroke. Spontaneously hypertensive rats received permanent middle cerebral artery occlusion. After 96 h, brain specimens were removed, fixed and stained for GFAP, glutamine synthetase (GS), S100Beta and Musashi1 (Msh1). Three regions of interest were defined (contralateral hemisphere, ipsilateral remote zone and infarct border zone), and confocal stacks were acquired (n=5 biological with each n=4 technical replicates). The stacks were background-corrected and colocalization between the selected markers and GFAP was determined using an automated thresholding algorithm. The fluorescence and colocalization channels were then converted into 3D-objects using both intensity and volume as filters to ultimately determine the final volumes of marker expression and colocalization, as well as the morphological changes of astrocyte process arborisation. We found that both S100Beta and Msh1 determined the same GFAP-positive astroglial cell population albeit the cellular compartments differed. GFAP stained most of the astrocyte processes and is hence suitable for the analysis of qualitative characteristics of astrogliosis. Due to its peri-nuclear localization, Msh1 is appropriate to estimate the total number of astrocytes even in regions with severe reactive astrogliosis. GS expression in GFAP-positive astrocytes was high in the remote zone and low at the infarct border, indicating the existence of astrocyte subclasses.Acta neurobiologiae experimentalis 01/2013; 73(1):79-87. -
Article: Human mesenchymal stem cells in the treatment of neurological diseases.
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ABSTRACT: Here we provide a comprehensive data on the unique features of mesenchymal stem cells (MSCs) which makes them feasible and preferred candidate for cell-based therapy in neurological clinic. From this point of view the most important features of these cells are: (1) availability from autologous sources independently from age of patient; (2) extensive expansion in vitro; (3) immunomodulatory "bystander" function after transplantation in vivo; (4) potentiality to protect, repair or eventually replace impaired or dysfunctional host cells. For complete this last task of functional regeneration of central nervous system, we have to take advantages of MSCs capability for transient, time-locked proliferation, migration to site of injury and their commitment to neuronal differentiation. However, if we are to make progress in the use of MSCs for therapy in the clinic it will be necessary to establish more unified, advanced standards for cells processing in vitro as well as safer and improved procedures for their delivery in vivo.Acta neurobiologiae experimentalis 01/2013; 73(1):38-56. -
Article: Treating spinal cord injury in rats with a combination of human fetal neural stem cells and hydrogels modified with serotonin.
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ABSTRACT: Currently, there is no effective strategy for the treatment of spinal cord injury (SCI). A combination of biomaterials and stem cell therapy seems to be a promising approach to increase regenerative potential after SCI. We evaluated the use of a cellpolymer construct based on a combination of the conditionally immortalized spinal progenitor cell line SPC-01_GFP3, derived from human fetal spinal cord tissue, with a serotonin-modified poly(2-hydroxyethyl methacrylate) hydrogel (pHEMA-5HT). We compared the effect of treatment with a pHEMA-5HT hydrogel seeded with SPC-01_GFP3 cells, treatment with a pHEMA-5HT only and no treatment on functional outcome and tissue reconstruction in hemisected rats. Prior to transplantation the cell-polymer construct displayed a high potential to support the growth, proliferation and differentiation of SPC-01 cells in vitro. One month after surgery, combined hydrogel-cell treatment reduced astrogliosis and tissue atrophy and increased axonal and blood vessel ingrowth into the implant; however, two months later only the ingrowth of blood vessels remained increased. SPC-01_GFP3 cells survived well in vivo and expressed advanced markers of neuronal differentiation. However, a majority of the transplanted cells migrated out of the lesion and only rarely remained in the hydrogel. No differences among the groups in motor or sensory recovery were observed. Despite the support of the hydrogel as a cell carrier in vitro, and good results in vivo one month postsurgery, there was only a small effect on long term recovery, mainly due to the limited ability of the hydrogels to support the in vivo growth and differentiation of cells within the implant. Further modifications will be necessary to achieve stable long term improvement in functional outcome.Acta neurobiologiae experimentalis 01/2013; 73(1):102-15. -
Article: Bone marrow stromal cell transplantation for ischemic stroke - its multi-functional feature.
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ABSTRACT: In this article, the author reviews recent advancements of basic research on bone marrow stromal cell (BMSC) transplantation for ischemic stroke. The BMSCs are easily isolated from the patients themselves and transplanted into them without any ethical and immunological problem. Animal experiments have shown that BMSC transplantation significantly enhance the recovery of motor and/or cognitive function in various types of neurological disorders such as ischemic stroke. The transplanted BMSCs aggressively migrate toward the damaged tissue and proliferate in the host brain. The BMSCs significantly improve the neuronal receptor function and local glucose metabolism in the peri-infarct area when transplanted into the infarct brain. Recent studies strongly suggest that the BMSCs contain heterogeneous subpopulations and contribute to functional recovery through multiple mechanisms, including neuroprotection, inflammatory modulation, cell fusion, and neural differentiation. The author describes the importance to establish BMSC transplantation as a therapeutic entity that is scientifically proven.Acta neurobiologiae experimentalis 01/2013; 73(1):57-65. -
Article: Epigenetic mechanisms of gene expression regulation in neurological diseases.
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ABSTRACT: Neurological diseases are a heterogenous group of disorders that are related to alterations in nervous system function. The genetic background of neurological diseases is heterogenous and may include chromosomal aberrations, specific gene mutations and epigenetic defects. This review is aimed at presenting of selected diseases that are associated with different epigenetic alterations. The imprinting defects on chromosome 15 are the cause of Prader-Willi and Angelman syndromes that both are characterized by intellectual disability, developmental delay and specific behavioral phenotype. Besides the imprinting defect, these diseases can also be caused by deletion of chromosome 15 or uniparental disomy. Aberrant epigenetic regulation is also specific for Fragile X syndrome that is caused by expansion of CGG repeats in the FMR1 gene that leads to global methylation of the promoter region and repression of FMR1 transcription. A number of neurological diseases, mainly associated with intellectual impairment, may be caused by mutations in genes encoding proteins involved in epigenetic regulation. The number of such diseases is rapidly growing thanks to the implementation of genomic sequencing for the identification of their molecular causes. One of the best known diseases linked to defects in epigenetic modifiers is Rett syndrome caused by a mutation in the MECP2 gene or its variant - Rett-like syndrome caused by a mutation in CDKL5 or FOXG1 genes. As the epigenetic signature is potentially reversible, much attention is focused on possible therapies with drugs that influence DNA or histone modifications. This is especially important in the case of neurological disorders in which epigenetic changes are observed as the effect of the disease.Acta neurobiologiae experimentalis 01/2013; 73(1):19-37. -
Article: Genetic engineering of stem cells for enhanced therapy.
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ABSTRACT: Stem cell therapy is a promising strategy for overcoming the limitations of current treatment methods. The modification of stem cell properties may be necessary to fully exploit their potential. Genetic engineering, with an abundance of methodology to induce gene expression in a precise and well-controllable manner, is particularly attractive for this purpose. There are virus-based and non-viral methods of genetic manipulation. Genome-integrating viral vectors are usually characterized by highly efficient and long-term transgene expression, at a cost of safety. Non-integrating viruses are also highly efficient in transduction, and, while safer, offer only a limited duration of transgene expression. There is a great diversity of transfectable forms of nucleic acids; however, for efficient shuttling across cell membranes, additional manipulation is required. Both physical and chemical methods have been employed for this purpose. Stem cell engineering for clinical applications is still in its infancy and requires further research. There are two main strategies for inducing transgene expression in therapeutic cells: transient and permanent expression. In many cases, including stem cell trafficking and using cell therapy for the treatment of rapid-onset disease with a short healing process, transient transgene expression may be a sufficient and optimal approach. For that purpose, mRNA-based methods seem ideally suited, as they are characterized by a rapid, highly efficient transfection, with outstanding safety. Permanent transgene expression is primarily based on the application of viral vectors, and, due to safety concerns, these methods are more challenging. There is active, ongoing research toward the development of non-viral methods that would induce permanent expression, such as transposons and mammalian artificial chromosomes.Acta neurobiologiae experimentalis 01/2013; 73(1):1-18. -
Article: Differentiation of glia-committed NG2 cells: The role of factors released from hippocampus and spinal cord.
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ABSTRACT: The NG2-positive cells are the oligodendrocyte precursors, which, when terminally differentiated, are capable of myelinating the central nervous system. There is however an ever-growing list of evidences that NG2 cells actually possess an intrinsic neurogenic potential and they are capable of neuronal differentiation in response to environmental stimuli. To address the question, we have established a model of an indirect co-culture system of the freshly isolated rat neonatal NG2 cells and organotypic slices derived from two distinct CNS regions (hippocampus and spinal cord) to mimic the nervous tissue microenviroment. The cell differentiation in microenvironment of OGD-injured hippocampal slices has been studied as well. The molecular analysis of selected trophic factors has been performed to determine the patterns of their expression. Indeed, the comparison of the cell commitment and development in various microenvironments has pointed to significant dissimilarities. First of all, the medium being continuously conditioned by the hippocampal slices efficiently promoted neurogenesis. The effect has been significantly abolished in co-cultures with the injured tissue. The less pronounced susceptibility to adopting neuronal phenotype and the considerable slowdown of oligodendroglial development was observed in the co-cultures with the spinal cord slices. The role of BDNF in oligodendroglial progenitor commitment and development has been investigated proving that it is one of the key players in the examined processes. The specificity of the instructive clues cocktail might module the fate choice of mobilized endogenous or transplanted cells, which should be taken into consideration while planning neurorepair strategies.Acta neurobiologiae experimentalis 01/2013; 73(1):116-29. -
Article: From otoacoustic emission to late auditory potentials P300: The inhibitory effect.
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ABSTRACT: This study verifies the effects of contralateral noise on otoacoustic emissions and auditory evoked potentials. Short, middle and late auditory evoked potentials as well as otoacoustic emissions with and without white noise were assessed. Twenty-five subjects, normal-hearing, both genders, aged 18 to 30 years, were tested . In general, latencies of the various auditory potentials were increased at noise conditions, whereas amplitudes were diminished at noise conditions for short, middle and late latency responses combined in the same subject. The amplitude of otoacoustic emission decreased significantly in the condition with contralateral noise in comparison to the condition without noise. Our results indicate that most subjects presented different responses between conditions (with and without noise) in all tests, thereby suggesting that the efferent system was acting at both caudal and rostral portions of the auditory system.Acta neurobiologiae experimentalis 01/2012; 72(3):296-308. -
Article: Endogenous neurogenesis induced by ischemic brain injury or neurodegenerative diseases in adults.
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ABSTRACT: The discovery of neurogenic response subsequent to brain injuries has led to the hypothesis that the expansion of the pool of endogenous progenitors could augment the regenerative capacity of the damaged areas. However, it occurred that endogenous spontaneous neurogenesis is insufficient for replacing the lost neurons and to achieve global repair, particularly in aging brain. Until today, a great effort has been made attempting to promote "reactive neurogenesis" more successful. It was found that small chemical molecules exert stimulation of neurogenesis and probably might help to induce neuronal endogenous cell replacement in various neurological diseases. In this review we briefly highlight the current data regarding effect of brain ischemia and age-related neurodegenerative diseases on neural stem cells in situ and potential therapeutic effect of their stimulation.Acta neurobiologiae experimentalis 01/2012; 72(4):309-24. -
Article: Patterning of human cord blood-derived stem cells on single cell posts and lines: Implications for neural commitment.
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ABSTRACT: Using stem cells (SC) in new strategies for clinical treatment requires control of stem cell fate decision and the ability to govern their patterning and commitment in tissue engineering. Neural stem cells and other adult SC can respond to the different components of the microenvironment and their spatial arrangement in the stem cell niche. It has been shown previously by our group that different composition and architecture of patterned bioactive domains influence the developmental response of neural stem cells. In the present report we verify the commitment and differentiation of neural stem cells derived from human cord blood (HUCB-NSC) by a single cell patterning system. Microcontact printing technology was used to generate single cell positioning areas of different geometry: 10 micrometer-thin lines and 10 micrometer-width one cell posts. The commitment and differentiation of HUCB-NSC cells cultured on different surfaces were dependent on the geometry and the type of biomaterial present in bioactive domains. Fibronectin promoted neuronal protrusion outgrowth (Beta-tubulin III and MAP-2 positive cells) and gap junction development (Cx43 marker) between cells growing on lines while poly-L-lysine promoted HUCB-NSC differentiation into astrocytic, glial fibrillary acidic protein expressing (GFAP positive) cell phenotype. Here we also demonstrate by scanning electron microscopy that morphology of cells on the patterned surface is highly dependent upon the type of biomolecules used for printing. These kinds of platforms can be used for investigating the influence of spatial organization of environment on the SC fate decision and for studying the molecular processes occurring in a single cell.Acta neurobiologiae experimentalis 01/2012; 72(4):325-36. -
Article: Association between plasma biomarkers, CDK5 polymorphism and the risk of Alzheimer's disease.
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ABSTRACT: In this study we evaluated biochemical blood serum parameters and the association of Cyclin-dependent kinase 5 (CDK5) gene polymorphisms with the risk of Alzheimer's disease (AD) in the Polish population. We observed an elevated total cholesterol, low-density lipoproteins (LDL) and homocysteine levels and lower concentrations of high-density lipoproteins (HDL) and vitamin B12 in AD patients. However, the analyzed CDK5 polymorphisms were not associated with the biochemical parameters. Moreover, we found no association between the studied polymorphisms and the risk of AD in the Polish population. The meta-analysis of previously published and current study was performed. In conclusion, our study demonstrated that alteration of cholesterol, LDL, HDL, homocysteine and B12 concentration may be an important factor in pathogenesis of AD.Acta neurobiologiae experimentalis 01/2012; 72(4):397-411. -
Article: Different strategies of exploration and phenotypic variability of the locomotor behavior in new environment: Comparative study of the laboratory opossum (Monodelphis domestica) and Wistar rat (Rattus norvegicus).
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ABSTRACT: Spontaneous locomotor activity of opossums and Wistar rats during a two-hour session in the open field has been recorded, assessed and behavior of individuals of the two species compared. Afterwards, groups of highly active (HA) and low active (LA) opossums and rats were selected on the basis of the distance traveled in the test. Differences between the selected groups were evaluated. Opossums were generally more active, moving faster and covering longer distance. They spent more time in the central part of the open field and traveled across the center more times than rats, therefore they showed also a lower level of anxiety. These data confirm our previous results indicating that opossums preferentially use the risky exploration strategy while rats mainly rely on the defensive behavior. Opossums showed a higher variability of the volume of locomotor activity than rats. Comparison of the HA and LA groups of opossums and rats showed that in each species they differed on another principle: the level of anxiety in Wistar rats and level of locomotor activity in opossums. Therefore results of the open field test might measure different parameters in different species.Acta neurobiologiae experimentalis 01/2012; 72(4):452-60. -
Article: The catechol-O-methyltransferase and monoamine oxidase B polymorphisms and levodopa therapy in the Iranian patients with sporadic Parkinson's disease.
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ABSTRACT: Parkinson's disease (PD) patients vary widely in their response to levodopa treatment, and this may be partially genetic in origin. Recent studies suggest that catechol-O-methyltransferase (COMT), G1947A and monoamine oxidase B (MAOB), A644G polymorphisms might influence the risk and treatment of PD. Herein, we aimed to test the possible influence of MAOB and COMT genetic polymorphisms on the effective daily dose of levodopa administered in the fifth year of treatment. We also examined the effect of COMT and MAOB haplotypes on levodopa therapy outcome. There were 31 females and 72 males of Iranian origin diagnosed with sporadic PD included into the study. The patients were divided into two groups. Group 1: patients received daily doses of levodopa below 500 mg in the fifth year of treatment. Group 2: those patients receiving daily doses exceeding 500 mg in the fifth year of treatment. MAOB and COMT polymorphism genotyping was performed by using PCR-based restriction fragment length polymorphism (RFLP) analyses. Our data show that the first group suffered less frequently from dyskinesia than patients from the second group. No statistically significant differences were found in allele frequencies and genotype distributions of the studied genes between two groups. In addition, the incidence of the specific haplotypes between the two groups did not show any difference. The present data suggest that pharmacokinetic or pharmacodynamic factors other than the investigated genetic variants of the MAOB and COMT enzymes seem to determine the response to levodopa in the Iranian PD patients.Acta neurobiologiae experimentalis 01/2012; 72(3):272-82. -
Article: Electrophysiological differences between high and low frequency rTMS protocols in depression treatment.
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ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is a rapidly expanding mean in drug resistant depression treatment. Yet, despite vast research in this field, exact neurophysiological mechanism of rTMS therapy still remains unclear. This results in difficulties choosing suitable rTMS parameters in advance and compromises thorough evaluation of efficacy after the treatment. In order to obtain more explicit assessment of rTMS therapy in the psychiatric field, we evaluated and compared the influence of two most widely used antidepressive rTMS protocols on EEG band power spectrum and relation to clinical test scores (MADRS, BDI, HAM-D17). Forty-five patients (12 male, 33 female, mean age 52.16 years) participated in the study. Twenty-three patients received high frequency (10 Hz) stimulation, the rest 22 were stimulated using low frequency (1 Hz) protocol. Both groups received 10 to 15 daily rTMS sessions. EEG recordings and clinical tests were obtained the day before rTMS course and same day after the last session. Majority (57.78%) of patients showed considerable improvement after the treatment. There were no notable differences in clinical test score drop between the two rTMS protocols. However, we found that different protocols resulted in significantly different electrophysiological changes. High frequency (10 Hz) rTMS resulted in widespread changes off EEG band power, including delta power increase on the left hemisphere and alpha power growth on the right. Theta power increase was also obtained in parietal-occipital areas. Low frequency (1 Hz) rTMS showed to have no major effect on basic EEG band power, however, we found a notable shift of frontal alpha power asymmetry towards the right hemisphere, which correlated with the clinical outcome. Our study results suggest that two widely used rTMS protocols strongly differ in their electrophysiological mechanisms. Low frequency stimulation finesse on frontal alpha power asymmetry shift, whereas high frequency protocol acts on wider electrophysiological changes in the brain.Acta neurobiologiae experimentalis 01/2012; 72(3):283-95.
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