Publications by authors named "Gabriele Zanirati"

14 Publications

  • Page 1 of 1

Left Hemisphere Lateralization of Epileptic Focus Can Be More Frequent in Temporal Lobe Epilepsy Surgical Patients with No Consensus Associated with Depression Lateralization.

Dev Neurosci 2021 31;43(1):1-8. Epub 2021 Mar 31.

Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.

Temporal lobe epilepsy (TLE) is considered to be the most common form of epilepsy, and it has been seen that most patients are refractory to antiepileptic drugs. A strong association of this ailment has been established with psychiatric comorbidities, primarily mood and anxiety disorders. The side of epileptogenic may contribute to depressive and anxiety symptoms; thus, in this study, we performed a systematic review to evaluate the prevalence of depression in TLE in surgical patients. The literature search was performed using PubMed/Medline, Web of Science, and PsycNet to gather data from inception until January 2019. The search strategy was related to TLE, depressive disorder, and anxiety. After reading full texts, 14 articles meeting the inclusion criteria were screened. The main method utilized for psychiatric diagnosis was Diagnostic and Statistical Manual of Mental Disorders/Structured Clinical Interview for DSM. However, most studies failed to perform the neuropsychological evaluation. For those with lateralization of epilepsy, focus mostly occurred in the left hemisphere. For individual depressive diagnosis, 9 studies were evaluated, and 5 for anxiety. Therefore, from the data analyzed in both situations, no diagnosis was representative in preoperative and postoperative cases. In order to estimate the efficacy of surgery in the psychiatry episodes and its relation to seizure control, the risk of depression and anxiety symptoms in epileptic patients need to be determined before surgical procedures. Rigorous preoperative and postoperative evaluation is essential for psychiatry conditions in patients with refractory epilepsy candidates for surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000513537DOI Listing
March 2021

Case Report: Placental Maternal Vascular Malperfusion Affecting Late Fetal Development and Multiorgan Infection Caused by SARS-CoV-2 in Patient With PAI-1 4G/5G Polymorphism.

Front Med (Lausanne) 2021 17;8:624166. Epub 2021 Feb 17.

Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.

Pregnant women are susceptible to the novel coronavirus (SARS-CoV-2), and the consequences for the fetus are still uncertain. Here, we present a case of a pregnant woman with subclinical hypothyroidism and a plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism who was infected with SARS-CoV-2 at the end of the third trimester of pregnancy, with unexpected evolution of death of the newborn 4 days postpartum. Nested PCR was performed to detect the virus, followed by ssDNA sequencing. Transplacental transmission of SARS-CoV-2 can cause placental inflammation, ischemia, and neonatal viremia, with complications such as preterm labor and damage to the placental barrier in patients with PAI-1 4G/5G polymorphism. We showed a newborn with several damages potentially caused due to the PAI-1 polymorphisms carried by the mother infected with SARS-CoV-2 during pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.624166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928274PMC
February 2021

Extracellular vesicles from human iPSC-derived neural stem cells: miRNA and protein signatures, and anti-inflammatory and neurogenic properties.

J Extracell Vesicles 2020 Aug 26;9(1):1809064. Epub 2020 Aug 26.

Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University College of Medicine, College Station, Texas, USA.

Grafting of neural stem cells (NSCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise for brain repair after injury or disease, but safety issues have hindered their clinical application. Employing nano-sized extracellular vesicles (EVs) derived from hiPSC-NSCs appears to be a safer alternative because they likely have similar neuroreparative properties as NSCs and are amenable for non-invasive administration as an autologous or allogeneic off-the-shelf product. However, reliable methods for isolation, characterization and testing the biological properties of EVs are critically needed for translation. We investigated signatures of miRNAs and proteins and the biological activity of EVs, isolated from hiPSC-NSCs through a combination of anion-exchange chromatography (AEC) and size-exclusion chromatography (SEC). AEC and SEC facilitated the isolation of EVs with intact ultrastructure and expressing CD9, CD63, CD81, ALIX and TSG 101. Small RNA sequencing, proteomic analysis, pathway analysis and validation of select miRNAs and proteins revealed that EVs were enriched with miRNAs and proteins involved in neuroprotective, anti-apoptotic, antioxidant, anti-inflammatory, blood-brain barrier repairing, neurogenic and Aβ reducing activities. Besides, EVs comprised miRNAs and/or proteins capable of promoting synaptogenesis, synaptic plasticity and better cognitive function. Investigations using an macrophage assay and a mouse model of status epilepticus confirmed the anti-inflammatory activity of EVs. Furthermore, the intranasal administration of EVs resulted in the incorporation of EVs by neurons, microglia and astrocytes in virtually all adult rat and mouse brain regions, and enhancement of hippocampal neurogenesis. Thus, biologically active EVs containing miRNAs and proteins relevant to brain repair could be isolated from hiPSC-NSC cultures, making them a suitable biologic for treating neurodegenerative disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/20013078.2020.1809064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480597PMC
August 2020

Long-term changes in metabolic brain network drive memory impairments in rats following neonatal hypoxia-ischemia.

Neurobiol Learn Mem 2020 05 5;171:107207. Epub 2020 Mar 5.

Preclinical Research Center, Brain Institute (BraIns) of Rio Grande do Sul, Porto Alegre, Brazil. Electronic address:

Background And Purpose: Hypoxia and cerebral ischemia (HI) events are capable of triggering important changes in brain metabolism, including glucose metabolism abnormalities, which may be related to the severity of the insult. Using positron emission microtomography (microPET) with [F]fluorodeoxyglucose (F-FDG), this study proposes to assess abnormalities of brain glucose metabolism in adult rats previously submitted to the neonatal HI model. We hypothesize that cerebral metabolic outcomes will be associated with cognitive deficits and magnitude of brain injury.

Methods: Seven-day-old rats were subjected to an HI model, induced by permanent occlusion of the right common carotid artery and systemic hypoxia. F-FDG-microPET was used to assess regional and whole brain glucose metabolism in rats at 60 postnatal days (PND 60). An interregional cross-correlation matrix was utilized to construct metabolic brain networks (MBN). Rats were also subjected to the Morris Water Maze (MWM) to evaluate spatial memory and their brains were processed for volumetric evaluation.

Results: Brain glucose metabolism changes were observed in adult rats after neonatal HI insult, limited to the right brain hemisphere. However, not all HI animals exhibited significant cerebral hypometabolism. Hippocampal glucose metabolism was used to stratify HI animals into HI hypometabolic (HI-h) and HI non-hypometabolic (HI non-h) groups. The HI-h group had drastic MBN disturbance, cognitive deficit, and brain tissue loss, concomitantly. Conversely, HI non-h rats had normal brain glucose metabolism and brain tissue preserved, but also presented MBN changes and spatial memory impairment. Furthermore, data showed that brain glucose metabolism correlated with cognitive deficits and brain volume outcomes.

Conclusions: Our findings demonstrated that long-term changes in MBN drive memory impairments in adult rats subjected to neonatal hypoxic ischemia, using in vivo imaging microPET-FDG. The MBN analyses identified glucose metabolism abnormalities in HI non-h animals, which were not detected by conventional F-FDG standardized uptake value (SUVr) measurements. These animals exhibited a metabolic brain signature that may explain the cognitive deficit even with no identifiable brain damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nlm.2020.107207DOI Listing
May 2020

The Interstitial System of the Brain in Health and Disease.

Aging Dis 2020 Feb 1;11(1):200-211. Epub 2020 Feb 1.

2Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.

The brain interstitial fluid (ISF) and the cerebrospinal fluid (CSF) cushion and support the brain cells. The ISF occupies the brain interstitial system (ISS), whereas the CSF fills the brain ventricles and the subarachnoid space. The brain ISS is an asymmetrical, tortuous, and exceptionally confined space between neural cells and the brain microvasculature. Recently, with a newly developed measuring technique, a series of discoveries have been made in the brain ISS and the drainage of ISF. The goal of this review is to confer recent advances in our understanding of the brain ISS, including its structure, function, and the various processes mediating or disrupting ISF drainage in physiological and pathological conditions. The brain ISF in the deep brain regions has recently been demonstrated to drain in a compartmentalized ISS instead of a highly connected system, together with the drainage of ISF into the cerebrospinal fluid (CSF) at the surface of the cerebral cortex and the transportation from CSF into cervical lymph nodes. Besides, accumulation of tau in the brain ISS in conditions such as Alzheimer's disease and its link to the sleep-wake cycle and sleep deprivation, clearance of ISF in a deep sleep via increased CSF flow, novel approaches to remove beta-amyloid from the brain ISS, and obstruction to the ISF drainage in neurological conditions are deliberated. Moreover, the role of ISS in the passage of extracellular vesicles (EVs) released from neural cells and the rapid targeting of therapeutic EVs into neural cells in the entire brain following an intranasal administration, and the promise and limitations of ISS based drug delivery approaches are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14336/AD.2020.0103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961771PMC
February 2020

Analysis of genes involved in cell proliferation, adhesion, and control of apoptosis during embryonic neurogenesis in Induced Pluripotent Stem Cells (iPSCs) from patients with Focal Cortical Dysplasia.

Brain Res Bull 2020 02 6;155:112-118. Epub 2019 Dec 6.

Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil; Graduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil; Graduate Program in Medicine, Pediatrics and Child Health, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil; School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil. Electronic address:

Focal cortical dysplasia (FCD) is a malformation of cortical development which is strongly associated with drug-refractory epilepsy. Certain studies have demonstrated an increase in mTOR signaling in patients with FCD on the basis of observation of phosphorylated molecules. The aim of the present study was to verify the differences in genes involved in cell proliferation, adhesion, and control of apoptosis during embryonic neurogenesis in iPSCs derived from the Focal Cortical Dysplasia. Fibroblasts were obtained from the skin biopsies of patients with FCD (n = 2) and controls (n = 2). iPSCs were generated by exposing the fibroblasts to viral vectors that contained the Yamanaka factors (OCT4, SOX2, KLF4, and c-MYC genes) responsible for promoving cell reprogramation. The fibroblasts and iPSCs were tested during different phases of neurodifferentiation for migration capacity and expression of the genes involved in the PI3K pathway. Fibroblasts of patients with FCD migrated with greater intensity during the first two time points of analyses. iPSCs did not exhibit any difference in cell migration between the groups. Fibroblasts, brain tissue, and iPSCs of the patients with FCD exhibited a significant reduction in the relative expression values of 4EBP-1. During neurodevelopment, the iPSCs from patients with FCD exhibited a reduction in the expression of cIAP-1, cIAP-2, PI3K, β-Catenin and 4EBP-1 gene. We suggest that the differences observed in the migration potential of adult cells and in the gene expression related to the fundamental processes involved in normal brain development during the neurodifferentiation process might be associated with cortical alteration in the patients with FCD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainresbull.2019.11.016DOI Listing
February 2020

A Model of Chronic Temporal Lobe Epilepsy Presenting Constantly Rhythmic and Robust Spontaneous Seizures, Co-morbidities and Hippocampal Neuropathology.

Aging Dis 2019 Oct 1;10(5):915-936. Epub 2019 Oct 1.

Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, TX, USA.

Many animal prototypes illustrating the various attributes of human temporal lobe epilepsy (TLE) are available. These models have been invaluable for comprehending multiple epileptogenic processes, modifications in electrophysiological properties, neuronal hyperexcitability, neurodegeneration, neural plasticity, and chronic neuroinflammation in TLE. Some models have also uncovered the efficacy of new antiepileptic drugs or biologics for alleviating epileptogenesis, cognitive impairments, or spontaneous recurrent seizures (SRS). Nonetheless, the suitability of these models for testing candidate therapeutics in conditions such as chronic TLE is debatable because of a lower frequency of SRS and an inconsistent pattern of SRS activity over days, weeks or months. An ideal prototype of chronic TLE for investigating novel therapeutics would need to display a large number of SRS with a dependable frequency and severity and related co-morbidities. This study presents a new kainic acid (KA) model of chronic TLE generated through induction of status epilepticus (SE) in 6-8 weeks old male F344 rats. A rigorous characterization in the chronic epilepsy period validated that the animal prototype mimicked the most salient features of robust chronic TLE. Animals displayed a constant frequency and intensity of SRS across weeks and months in the 5th and 6th month after SE, as well as cognitive and mood impairments. Moreover, SRS frequency displayed a rhythmic pattern with 24-hour periodicity and a consistently higher number of SRS in the daylight period. Besides, the model showed many neuropathological features of chronic TLE, which include a partial loss of inhibitory interneurons, reduced neurogenesis with persistent aberrant migration of newly born neurons, chronic neuroinflammation typified by hypertrophied astrocytes and rod-shaped microglia, and a significant aberrant mossy fiber sprouting in the hippocampus. This consistent chronic seizure model is ideal for investigating the efficacy of various antiepileptic drugs and biologics as well as understanding multiple pathophysiological mechanisms underlying chronic epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14336/AD.2019.0720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764729PMC
October 2019

Evaluation of miR-135a/b expression in endometriosis lesions.

Biomed Rep 2019 Oct 2;11(4):181-187. Epub 2019 Sep 2.

School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil.

The pathogenesis of endometriosis is not clear; however, microRNAs (miRNAs/miRs) are involved in the pathogenesis. miRNAs are short noncoding RNAs involved in post-transcriptional regulation of gene expression by silencing the expression of target genes. The expression of is associated with endometrial receptivity and implantation; the expression is also associated with the expression of certain genes, including homeobox protein Hox-A10 (. The present study investigated the expression of / in eutopic and ectopic endometrium tissues throughout the different phases of the menstrual cycle. Samples of ectopic endometriosis lesions and eutopic endometrium tissue from 23 patients who underwent laparoscopic surgery were obtained and analyzed. miRNA was extracted and the expression levels of were determined by reverse transcription quantitative polymerase chain reaction assays using U6 as a housekeeping control. The expression levels of and in endometriosis lesions were decreased compared with the levels in endometrium tissue. However, expression levels were increased in the secretory phase compared with the proliferative phase in endometriosis lesions. The increased expression of during the secretory phase compared with the proliferative phase suggested that these genes serve a determinant role in the homeostasis of reproductive tissue. Therefore, the expression of genes may affect endometrial functioning, impairing embryo implantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/br.2019.1237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759580PMC
October 2019

Umbilical Mononuclear Cells and Fibroblast Interaction Downregulate the Expression of Cell Cycle Negative Control Genes.

Cell Reprogram 2018 10 11;20(5):320-327. Epub 2018 Sep 11.

1 Brain Institute of Rio Grande do Sul (BraIns) , Porto Alegre, Brazil .

The human umbilical cord blood (HUCB) is an excellent source of adult stem cells, having the benefit of being younger than the bone marrow stem cells. The role of stem cells in the lesion repair mechanism is still being studied. We evaluated the capability of HUCB to interfere into the fibroblast dedifferentiation plasticity through cocultivation. Direct and indirect cocultures were maintained for 24, 48, and 72 hours. Coculture viability was evaluated by MTT assay. The messenger RNA was extracted, and the expression of p16 and p21 genes was estimated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The direct or indirect contact did not interfere with fibroblast cell viability. However, these direct and indirect contacts reduced the expression of p16 and p21 genes. A sigmoidal curve was applied to adjust gene expression against time, and a mathematical function was established for gene expression according to cell culture type. These results suggest that the differentiated cells were influenced by immature cells (HUCB) either by the direct contact or by signaling molecules, which alter their behavior and plasticity. Therefore our data may contribute to paracrine effects other than the commonly known to be responsible for the repair of lesions in stem cell therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/cell.2018.0014DOI Listing
October 2018

Depression comorbidity in epileptic rats is related to brain glucose hypometabolism and hypersynchronicity in the metabolic network architecture.

Epilepsia 2018 05 30;59(5):923-934. Epub 2018 Mar 30.

Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.

Objective: Temporal lobe epilepsy (TLE) is one of the most common types of epilepsy syndromes in the world. Depression is an important comorbidity of epilepsy, which has been reported in patients with TLE and in different experimental models of epilepsy. However, there is no established consensus on which brain regions are associated with the manifestation of depression in epilepsy. Here, we investigated the alterations in cerebral glucose metabolism and the metabolic network in the pilocarpine-induced rat model of epilepsy and correlated it with depressive behavior during the chronic phase of epilepsy.

Methods: Fluorodeoxyglucose ( F-FDG) was used to investigate the cerebral metabolism, and a cross-correlation matrix was used to examine the metabolic network in chronically epileptic rats using micro-positron emission tomography (microPET) imaging. An experimental model of epilepsy was induced by pilocarpine injection (320 mg/kg, ip). Forced swim test (FST), sucrose preference test (SPT), and eating-related depression test (ERDT) were used to evaluate depression-like behavior.

Results: Our results show an association between epilepsy and depression comorbidity based on changes in both cerebral glucose metabolism and the functional metabolic network. In addition, we have identified a significant correlation between brain glucose hypometabolism and depressive-like behavior in chronically epileptic rats. Furthermore, we found that the epileptic depressed group presents a hypersynchronous brain metabolic network in relation to the epileptic nondepressed group.

Significance: This study revealed relevant alterations in glucose metabolism and the metabolic network among the brain regions of interest for both epilepsy and depression pathologies. Thus it seems that depression in epileptic animals is associated with a more diffuse hypometabolism and altered metabolic network architecture and plays an important role in chronic epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.14057DOI Listing
May 2018

Transplantation of bone marrow mononuclear cells prolongs survival, delays disease onset and progression and mitigates neuronal loss in pre-symptomatic, but not symptomatic ALS mice.

Neurosci Lett 2016 10 22;633:182-188. Epub 2016 Sep 22.

Centro de Pesquisa Pré-Clínica, Instituto do Cérebro do Rio Grande do Sul - Brain Institute (BraIns), Porto Alegre, RS, Brazil; Laboratório de Neurociências, Instituto do Cérebro do Rio Grande do Sul - Brain Institute (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil. Electronic address:

Cell-based therapy provides a novel strategy to restore lost neurons or modulate the degenerating microenvironment in amyotrophic lateral sclerosis (ALS). This study verified the therapeutic potential of bone marrow mononuclear cells (BMMCs) in SOD1 mice. BMMCs were obtained from enhanced green fluorescent protein (EGFP) transgenic C57BL/6 mice (BMMCs) or from SOD1 transgenic mice (BMMCs) and given to mice at the pre-symptomatic or late symptomatic stage. Survival, body weight and motor performance data were recorded. DNA integrity was evaluated using the alkaline comet assay. The spinal cords were collected to assess motoneuron preservation and cell migration. BMMCs and BMMCs transplantation to pre-symptomatic SOD1 mice prolonged survival and delayed disease progression. The effects were more significant for the BMMC-transplanted mice. In late symptomatic mice, BMMCs promoted a discrete increase in survival, without other clinical improvements. DNA from BMMCs and BMMCs was found in the spinal cords of transplanted animals. DNA damage was not modified by BMMCs in any of the studied groups. Despite positive behavioral effects observed in our study, the limited results we observed for late transplanted mice call for caution before clinical application of BMMCs in ALS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neulet.2016.09.030DOI Listing
October 2016

Neural Stem Cell or Human Induced Pluripotent Stem Cell-Derived GABA-ergic Progenitor Cell Grafting in an Animal Model of Chronic Temporal Lobe Epilepsy.

Curr Protoc Stem Cell Biol 2016 08 17;38:2D.7.1-2D.7.47. Epub 2016 Aug 17.

Institute for Regenerative Medicine, Texas A&M University Health Science Center College of Medicine, Temple, Texas.

Grafting of neural stem cells (NSCs) or GABA-ergic progenitor cells (GPCs) into the hippocampus could offer an alternative therapy to hippocampal resection in patients with drug-resistant chronic epilepsy, which afflicts >30% of temporal lobe epilepsy (TLE) cases. Multipotent, self-renewing NSCs could be expanded from multiple regions of the developing and adult brain, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). On the other hand, GPCs could be generated from the medial and lateral ganglionic eminences of the embryonic brain and from hESCs and hiPSCs. To provide comprehensive methodologies involved in testing the efficacy of transplantation of NSCs and GPCs in a rat model of chronic TLE, NSCs derived from the rat medial ganglionic eminence (MGE) and MGE-like GPCs derived from hiPSCs are taken as examples in this unit. The topics comprise description of the required materials, reagents and equipment, methods for obtaining rat MGE-NSCs and hiPSC-derived MGE-like GPCs in culture, generation of chronically epileptic rats, intrahippocampal grafting procedure, post-grafting evaluation of the effects of grafts on spontaneous recurrent seizures and cognitive and mood impairments, analyses of the yield and the fate of graft-derived cells, and the effects of grafts on the host hippocampus. © 2016 by John Wiley & Sons, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cpsc.9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313261PMC
August 2016

Transplantation of bone marrow mononuclear cells modulates hippocampal expression of growth factors in chronically epileptic animals.

CNS Neurosci Ther 2015 May 29;21(5):463-71. Epub 2015 Jan 29.

PUCRS, Pós-Graduação em Medicina e Ciências da Saúde, Instituto do Cérebro do Rio Grande do Sul (InsCer), Instituto de Pesquisas Biomódicas, Laboratório de Neurociências e Sinalização Celular, Porto Alegre, RS, Brazil.

Aims: In previous studies, transplantation of bone marrow mononuclear cells (BMMCs) in epileptic animals has been found to be neuroprotective. However, the mechanism by which the BMMCs act remains unclear. We hypothesize that BMMCs may provide neuroprotection to the epileptic brain through trophic support. To test our hypothesis, we studied the temporal expression of neurotrophins after BMMC transplantation in the epileptic rat hippocampus.

Methods: Chronically epileptic rats were intravenously transplanted with 1 × 10(7) BMMCs isolated from GFP transgenic mice. Expression levels of BDNF, GDNF, NGF, VEGF, and TGF-β1, and their receptors, were evaluated by ELISA and/or qRT-PCR analysis.

Results: Our data revealed increased protein expression of BDNF, GDNF, NGF, and VEGF and reduced levels of TGF-β1 in the hippocampus of transplanted epileptic animals. Additionally, an increase in the mRNA expression of BDNF, GDNF, and VEGF, a reduction in TGF-β1, and a decrease in mRNA levels of the TrkA and TGFR-β1 receptors were also observed.

Conclusion: The gain provided by transplanted BMMCs in the epileptic brain may be related to the ability of these cells in modulating the network of neurotrophins and angiogenic signals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cns.12382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495300PMC
May 2015

Bone marrow mononuclear cells reduce seizure frequency and improve cognitive outcome in chronic epileptic rats.

Life Sci 2011 Aug 22;89(7-8):229-34. Epub 2011 Jun 22.

Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Aims: Epilepsy affects 0.5-1% of the world's population, and approximately a third of these patients are refractory to current medication. Given their ability to proliferate, differentiate and regenerate tissues, stem cells could restore neural circuits lost during the course of the disease and reestablish the physiological excitability of neurons. This study verified the therapeutic potential of bone marrow mononuclear cells (BMMCs) on seizure control and cognitive impairment caused by experimentally induced epilepsy.

Main Methods: Status epilepticus (SE) was induced by lithium-pilocarpine injection and controlled with diazepam 90 min after SE onset. Lithium-pilocarpine-treated rats were intravenously transplanted 22 days after SE with BMMCs obtained from enhanced green fluorescent protein (eGFP) transgenic C57BL/6 mice. Control epileptic animals were given an equivalent volume of saline or fibroblast injections. Animals were video-monitored for the presence of spontaneous recurrent seizures prior to and following the cell administration procedure. In addition, rats underwent cognitive evaluation using a Morris water maze.

Key Findings: Our data show that BMMCs reduced the frequency of seizures and improved the learning and long-term spatial memory impairments of epileptic rats. EGFP-positive cells were detected in the brains of transplanted animals by PCR analysis.

Significance: The positive behavioral effects observed in our study indicate that BMMCs could represent a promising therapeutic option in the management of chronic temporal lobe epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2011.06.006DOI Listing
August 2011
-->