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INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia among the elderly population. AD is accompanied with the dysregulation of specific neurotrophic factors (NTFs) and their receptors, which plays a critical role in neuronal degeneration. NTFs are small proteins with therapeutic potential for human neurodegenerative diseases. These growth factors are categorized into four families: neurotrophins, neurokines, the glial cell line-derived NTF family of ligands, and the newly discovered cerebral dopamine NTF/mesencephalic astrocyte-derived NTF family. NTFs are capable of preventing cell death in degenerative conditions and can increase the neuronal growth and function in these disorders. Nevertheless, the adverse side effects of NTFs delivery and poor diffusion of these factors in the brain restrict the efficacy of NTFs therapy in clinical situations. MATERIALS AND METHODS: In this review, we focus on the current advances in the use of NTFs to treat AD and summarize previous experimental and clinical studies for supporting the protective and therapeutic effects of these factors. CONCLUSION: Based on reports, NTFs are considered as new and promising candidates for treating AD and AD-associated cognitive impairment.
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Doença de Alzheimer , Fatores de Crescimento Neural , Idoso , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Humanos , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/uso terapêuticoRESUMO
BACKGROUND: Cerebral ischemic stroke can induce the proliferation of subventricular zone (SVZ) neural stem cells (NSCs) in the adult brain. However, this reparative process is restricted because of NSCs' death shortly after injury or disability of them to reach the infarct boundary. In the present study, we investigated the ability of cerebral dopamine neurotrophic factor (CDNF) on the attraction of SVZ-resident NSCs toward the lesioned area and neurological recovery in a photothrombotic (PT) stroke model of mice METHODS: The mice were assigned to three groups stroke, stroke+phosphate buffered saline (PBS), and stroke+CDNF. Migration of SVZ NSCs were evaluated by BrdU/doublecortin (DCX) double immunofluorescence method on days 7 and 14 and their differentiation were evaluated by BrdU/ Neuronal Nuclei (NeuN) double immunofluorescence method 28 days after intra-SVZ CDNF injection. Serial coronal sections were stained with cresyl violet to detect the infarct volume and a modified neurological severity score (mNSS) was performed to assess the neurological performance RESULTS: Injection of CDNF increased the proliferation of SVZ NSCs and the number of DCX-expressing neuroblasts migrated from the SVZ toward the ischemic site. It also enhanced the differentiation of migrated neuroblasts into the mature neurons in the lesioned site. Along with this, the infarct volume was significantly decreased and the neurological performance was improved as compared to other groups CONCLUSION: These results demonstrate that CDNF is capable of enhancing the proliferation of NSCs residing in the SVZ and their migration toward the ischemia region and finally, differentiation of them in stroke mice, concomitantly decreased infarct volume and improved neurological abilities were revealed.
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Células-Tronco Neurais , Acidente Vascular Cerebral , Animais , Camundongos , Ventrículos Laterais , Dopamina , Bromodesoxiuridina , Proliferação de Células , Fatores de Crescimento Neural , Proteínas do Domínio Duplacortina , Infarto , Fosfatos , Neurogênese/fisiologiaRESUMO
Electromagnetic fields (EMFs) could induce oxidative stress (OS) in human tissues. Lipid peroxidation (LPO) is the main hallmark of OS that harms neural cell components, primarily lipids in the myelin sheaths and membranes. Vitamin E is a lipophilic antioxidant that protects cells from OS-related damages and inhibits the LPO process. In this study, male rats were assigned into three groups of Control, EMF, and EMF+ Vitamin E. The EMF producer equipment produced an alternate current of 50 Hz, 3 Mili Tesla (mT). At the end of the experiment, half of the substantia nigra in every sample was used for measurement of the malondialdehyde (MDA) level as the end-product of the LPO and activity of superoxide dismutase (SOD) enzyme. The next half of the tissue was prepared for transmission electron microscopy (TEM). In the EMF group, MDA level was enhanced and SOD value decreased significantly compared to the control group, but Vitamin E could restore these changes. In rats undergone EMF, heterochromatic nucleus and destruction in some portions of the nuclear membrane were detected. The segmental separation or destruction of myelin sheath lamellae was observed in nerve fibers. In treated animals, the nucleus was round, less heterochromatic, with a regular membrane. Separation of myelin sheath lamellae in some nerve fibers was slighter than the radiation group. Considering the results, EMF exposure induces LPO and triggers ultrastructural changes in the cell membranes, nucleus, and myelin sheath of substantia nigra cells, but Vitamin E consumption weakens these neuropathological alterations.
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Campos Eletromagnéticos , Fármacos Neuroprotetores , Animais , Campos Eletromagnéticos/efeitos adversos , Masculino , Malondialdeído , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Ratos , Substância Negra , Vitamina E/farmacologiaRESUMO
In the adult mammalian brain, new functional neurons are generated throughout life because of sustained proliferation and differentiation of neural stem cells (NSCs). The subventricular zone (SVZ), lining the lateral ventricle, and the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus are the two major neurogenic regions in the adult brain. This process is not fixed but is highly modulated by numerous intrinsic and extrinsic factors. Neurogenesis has become in the focus of interest for its involvement in repairing the damaged brain and this motivates researchers to detect controlling mechanisms of this process. Recent evidence suggests that alcohol usage can directly influence adult hippocampal neurogenesis, but its mechanisms remain a matter for debate. Thus, this review summarizes in vivo/in vitro studies on the role of alcohol in hippocampal neurogenesis during adulthood and clarifies its underlying mechanisms by highlighting neurotransmitters and their receptors.
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Alcoolismo/patologia , Hipocampo/patologia , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Alcoolismo/psicologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Etanol/administração & dosagem , Etanol/toxicidade , Hipocampo/efeitos dos fármacos , Humanos , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/patologia , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Neurônios/fisiologiaRESUMO
In the present study paclitaxel (taxol) was labeled with [99m Tc(CO)3 (H2 O)3 ]+ core. Labeling was optimized, and radiochemical analysis was determined by thin layer chromatography and high performance liquid chromatography. Radiocomplex was evaluated and verified further as a tumor characterization agent in B16-F10 melanoma tumor-bearing mice. The [99m Tc(CO)3 (H2 O)3 ]+ -paclitaxel complex with high specific activity (0.77 GBq/µmol) and labeling yield (96.8 ± 1.3) was obtained. No decrease in labeling was observed up to 6 hours, and the stability of the radiocomplex was found adequate. Our main achievement was high accumulation of radiolabeled paclitaxel in tumor (4.51 ± 0.65 percentage injected dose per gram [%ID/g] at 2-h postinjection) followed by significant reduction (1.86 ± 0.27%ID/g) at 4-hour postinjection. Because paclitaxel is a substrate for multidrug resistance, 99m Tc-tricarbonyl-paclitaxel imaging would be useful for tumor characterization rather than tumor detection.
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Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Microtúbulos/efeitos dos fármacos , Compostos de Organotecnécio/química , Paclitaxel/química , Paclitaxel/farmacologia , Animais , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Humanos , Marcação por Isótopo , Camundongos , Microtúbulos/metabolismo , Paclitaxel/farmacocinética , Paclitaxel/uso terapêutico , Radioquímica , Distribuição TecidualRESUMO
BACKGROUND: Infection with parvovirus B19 may cause fetal losses including spontaneous abortion, intrauterine fetal death and non-immune hydrops fetalis. The aim of this study is to determine the frequency of parvovirus B19 in formalin fixed placental tissues in lost fetuses using real-time PCR method. METHODS: In this cross-sectional study, 100 formalin fixed placental tissues with unknown cause of fetal death were determined using real-time PCR method after DNA extraction. RESULTS: Six out of 100 cases (6%) were positive for parvovirus B19 using real-time PCR. Gestational age of all positive cases was less than 20 weeks with a mean of 12.3 weeks. Three cases have a history of abortion and all of positive cases were collected in spring. Mean age of positive cases were 28 years. CONCLUSION: Parvovirus B19 during pregnancy can infect red precursor cells and induces apoptosis or lyses these cells that resulting in anemia and congestive heart failure leading to fetal death. Management of parvovirus B19 infection in pregnant women is important because immediate diagnosis and transfusion in hydropsic fetuses can decrease the risk of fetal death.
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Endoglin (ENG) mutation causes type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22αCre leads to AVM development in the brain and other organs. We hypothesized that an increase in Eng- negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon-improved cre (icre), which is more potent in recombination of the floxed alleles than the wild-type (WT) cre. R26RCreER;Engf/f mice that have a Rosa promoter driving and tamoxifen (TM)-inducible WT cre expression globally, and PdgfbiCreER;Engf/f mice that have a Pdgfb promoter driving and TM-inducible icre expression in ECs were treated with three intra-peritoneal injections of TM (2.5 mg/25 g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that icre caused more Eng deletion in the brain, indicated by a lower level of Eng proteins (p < 0.001) and fewer Eng-positive ECs (p = 0.01) than mice with WT cre. Mice with icre-mediated Eng deletion have more abnormal vessels (p = 0.02), CD68+ macrophages (p = 0.002), and hemorrhage (p = 0.04) and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that has not been detected in WT cre mice before. RNA-seq analysis showed that 8 out of the 10 top upregulated pathways identified by gene ontology (GO) analysis are related to inflammation. Therefore, the increase in Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng-negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients.
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Nosebleeds and intracranial hemorrhage from brain arteriovenous malformations (bAVMs) are among the most devastating symptoms of patients with hereditary hemorrhagic telangiectasis (HHT). All available managements have limitations. We showed that intravenous delivery of soluble FMS-related tyrosine kinase 1 using an adeno-associated viral vector (AAV9-sFLT1) reduced bAVM severity of endoglin deficient mice. However, minor liver inflammation and growth arrest in young mice were observed. To identify AAV variants and delivery methods that can best transduce brain and nasal tissue with an optimal transduction profile, we compared 3 engineered AAV capsids (AAV.cc47, AAV.cc84 and AAV1RX) with AAV9. A single-stranded CBA promoter driven tdTomato transgene was packaged in these capsids and delivered intravenously (i.v.) or intranasally (i.n.) to wild-type mice. A CMV promoter driven Alk1 transgene was packaged into AAV.cc84 and delivered to PdgfbiCre;Alk1 f/f mice through i.v. injection followed by brain AVM induction. Transduced cells in different organs, vessel density and abnormal vessels in the bAVMs, and liver inflammation were analyzed histologically. Liver and kidney function were measured enzymatically. Compared to other viral vectors, AAV.cc84, after i.v. delivery, transduced a high percentage of brain ECs and few hepatocytes; whereas after i.n. delivery, AAV.cc84 transduced ECs and perivascular cells in the brain, and ECs, epithelial cells, and skeletal muscles in the nose with minimum hepatocyte transduction. No changes to liver or kidney function were detected. Delivery of AAV.cc84-Alk1 through i.v. to PdgfbiCre;Alk1 f/f mice reduced bAVM severity. In summary, we propose that AAV.cc84-Alk1 is a promising candidate for developing gene therapy in HHT patients.
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Nosebleeds and intracranial hemorrhage from brain arteriovenous malformations (bAVMs) are among the most devastating symptoms of patients with hereditary hemorrhagic telangiectasis (HHT). All available managements have limitations. We showed that intravenous (i.v.) delivery of soluble Feline McDonough Sarcoma (FMS)-related tyrosine kinase 1 using an adeno-associated viral vector (AAV9-sFLT1) reduced bAVM severity of endoglin deficient mice. However, minor liver inflammation and growth arrest in young mice were observed. To identify AAV variants and delivery methods that can best transduce brain and nasal tissue with an optimal transduction profile, we compared 3 engineered AAV capsids (AAV.cc47, AAV.cc84, and AAV1RX) with AAV9. A single-stranded CBA promoter driven tdTomato transgene was packaged in these capsids and delivered i.v. or intranasally (i.n.) to wild-type mice. A CMV promoter driven Alk1 transgene was packaged into AAV.cc84 and delivered to PdgfbiCre;Alk1f/f mice through i.v. followed by bAVM induction. Transduced cells in organs, vessel density, abnormal vessels in the bAVMs, and liver inflammation were analyzed histologically. Liver and kidney function were measured enzymatically. Compared to other viral vectors, AAV.cc84, after i.v. delivery, transduced a high percentage of brain endothelial cells (ECs) and few hepatocytes; whereas after i.n. delivery, AAV.cc84 transduced ECs and perivascular cells in the brain, and ECs, epithelial cells, and muscles in the nose with minimum hepatocyte transduction. No changes to liver or kidney function were detected. The delivery of AAV.cc84-Alk1 through i.v. to PdgfbiCre;Alk1f/f mice reduced bAVM severity. In summary, we propose that AAV.cc84-Alk1 is a promising candidate for developing gene therapy in HHT patients.
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Background: The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. Hypotheses: The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. Method: COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 (n = 7) or endoglin (n = 7) deleted in the endothelial cells or brain focally (n = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. Results: The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. Conclusions: The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage.
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Malformações Arteriovenosas , Células Endoteliais , Humanos , Animais , Camundongos , Encéfalo , Hemorragia/complicações , Colágeno Tipo IRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and a member of the corona virus family, primarily affecting the upper respiratory system and the lungs. Like many other respiratory viruses, SARS-CoV-2 can spread to other organ systems. Apart from causing diarrhea, another very common but debilitating complication caused by SARS-CoV-2 is neurological symptoms and cognitive difficulties, which occur in up to two thirds of hospitalized COVID-19 patients and range from shortness of concentration and overall declined cognitive speed to executive or memory function impairment. Neuro-cognitive dysfunction and "brain fog" are frequently present in COVID-19 cases, which can last several months after the infection, leading to disruption of daily life. Cumulative evidence suggests that SARS-CoV-2 affects vasculature in the extra-pulmonary systems directly or indirectly, leading to impairment of endothelial function and even multi-organ damage. The post COVID-19 long-lasting neurocognitive impairments have not been studied fully and their underlying mechanism remains elusive. In this review, we summarize the current understanding of the effects of COVID-19 on vascular dysfunction and how vascular dysfunction leads to cognitive impairment in patients.
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Most scholars support the increase in carbon dioxide (CO2) emissions as one of the major causes of the increase in global climate change. Therefore, reducing CO2 emissions from the main emitter countries, including Iran as the sixth emitter, is important to deal with the harmful effects of global climate change. Accordingly, the main aim of this paper was to analyze the social, economic, and technical factors affecting CO2 emissions in Iran. Previous studies on diverse variables affecting emissions are not very accurate and reliable as they do not consider indirect effects. This study applied a structural equation model (SEM) to estimate the direct and indirect impacts of factors on the emissions by panel data for 28 provinces of Iran from 2003 to 2019. According to geographical location, three distinct regions, the north, center, and south of Iran were considered. The findings suggest that a 1% increase in social factor directly increased CO2 emissions by 2.23% (in the north) and 1.58% (in the center), but indirectly reduced emissions by 0.41% (in the north) and 0.92% (in the center). Hence, the total effects of the social factor on CO2 emissions were estimated at 1.82%, and 0.66% in the northern, and central regions, respectively. In addition, the total effects of the economic factor on CO2 emissions were estimated at 1.52%, and 0.73% in those regions. The results of this study showed that the direct effects of a technical factor on CO2 emissions were negative in the north and center. However, they were positive in the south of Iran. Based on the empirical results of this study, three policy implications are discussed in order to control CO2 emissions in regional distinctions of Iran as follows: First, policymakers should pay attention to the social factor, i.e., the growth of human capital in the southern region with the aim of increasing sustainable development. Second, Iranian policymakers must prevent unilaterally increasing gross domestic product (GDP) and financial development in the north and center. Third, policymakers should pay attention to the technical factor, i.e., improving energy efficiency, as well as upgrading information and communications technology (ICT) in the northern and central regions, and limiting the technical factor in the southern region.
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Dióxido de Carbono , Desenvolvimento Econômico , Humanos , Irã (Geográfico) , Dióxido de Carbono/análise , Comunicação , Produto Interno BrutoRESUMO
BACKGROUND: Photothrombotic (PT) stroke model is a reliable method to induce ischemic stroke in the target site using the excitation of photosensitive agents such as Rose Bengal (RB) dye after light illumination. Here, we performed a PT-induced brain ischemic model using a green laser and photosensitive agent RB and confirmed its efficiency through cellular, histological, and neurobehavioral approaches. METHODS: Mice were randomly allocated into RB; Laser irradiation; and RB + Laser irradiation groups. Mice were exposed to a green laser at a wavelength of 532 nm and intensity of 150 mW in a mouse model after injection of RB under stereotactic surgery. The pattern of Hemorrhagic and ischemic changes were evaluated throughout the study. The volume of the lesion site was calculated using unbiased stereological methods. For investigation of neurogenesis, we performed double - (BrdU/NeuN) immunofluorescence (IF) staining on day 28 following the last- BrdU injection. To assess the effect and quality of ischemic stroke on neurological behavior, the Modified neurological severity score (mNSS) test was done on days 1, 7, 14, and 28 days after stroke induction. RESULTS: Laser irradiation plus RB induced hemorrhagic tissue and pale ischemic changes over the 5 days. In the next few days, microscopic staining revealed neural tissue degeneration, demarcated necrotic site, and neuronal injury. BrdU staining showed a significant number of proliferating cells in the periphery of the lesion site in the Laser irradiation plus RB group compared to the group (p < 0.05) while the percent of NeuN+ cells per BrdU- positive cells was reduced. Also, prominent astrogliosis was observed in the periphery of irradiated sites on day 28. Neurological deficits were detected in mice from Laser irradiation plus the RB group. No histological or functional deficits were detected in RB and Laser irradiation groups. CONCLUSIONS: Taken together, our study showed cellular and histologic pathological changes which are associated with the PT induction model. Our findings indicated that the undesirable microenvironment and inflammatory conditions could affect neurogenesis concomitantly with functional deficits. Moreover, this research showed that this model is a focal, reproducible, noninvasive and accessible stroke model with a distinctive demarcation similar to human stroke conditions.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Camundongos , Animais , Bromodesoxiuridina/farmacologia , Acidente Vascular Cerebral/patologia , Neurônios/patologia , Neurogênese , Modelos Animais de Doenças , Isquemia Encefálica/patologiaRESUMO
Government control distorts energy prices which leads to loss of optimal factor combination and, as a result, affects efficiency. Previous researches on energy price distortions did not pay attention to the allocative efficiency specifically. In this paper, we empirically estimate the impact of energy carriers' price distortion on allocative efficiency in 28 Iranian provinces during 2002-2015 using Stochastic Frontier Analysis (SFA). Results indicate that energy carriers' price distortions affect allocative efficiency negatively. However, allocative efficiency increased in 2011 due to the energy price reform of 2010; it showed a downward trend in the following years which means that energy price reform was effective only in the short-term. The energy price distortion trend and inefficiency changes are similar in all regions; nonetheless, there are differences in the measures caused by differences in energy consumption, the existence of energy-intensive industries, and technical barriers. Furthermore, among the 28 provinces which are classified to 5 regions, region 2 has the lowest and region 3 has the biggest price distortion during the same period.
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Eficiência , Indústrias , Irã (Geográfico) , Alocação de RecursosRESUMO
Brain arteriovenous malformations (bAVMs) are abnormal vessels that are prone to rupture, causing life-threatening intracranial bleeding. The mechanism of bAVM formation is poorly understood. Nevertheless, animal studies revealed that gene mutation in endothelial cells (ECs) and angiogenic stimulation are necessary for bAVM initiation. Evidence collected through analyzing bAVM specimens of human and mouse models indicate that cells other than ECs also are involved in bAVM pathogenesis. Both human and mouse bAVMs vessels showed lower mural cell-coverage, suggesting a role of pericytes and vascular smooth muscle cells (vSMCs) in bAVM pathogenesis. Perivascular astrocytes also are important in maintaining cerebral vascular function and take part in bAVM development. Furthermore, higher inflammatory cytokines in bAVM tissue and blood demonstrate the contribution of inflammatory cells in bAVM progression, and rupture. The goal of this paper is to provide our current understanding of the roles of different cellular loci in bAVM pathogenesis.
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It is essential to study CO2 emissions intensity as the most critical factor affecting temperature increase and climate change in a country like Iran, which ranked seven regarding CO2 emissions intensity. Investigating the convergence of CO2 emissions intensity is essential in recognizing its dynamics in identifying the effectiveness of government environmental policies. In this paper, using the Markov chain and spatial Markov chain methods, the convergence of CO2 emissions intensity from fossil-fuel consumption has been investigated in 28 provinces of Iran from 2002 to 2016. The empirical results showed that convergence clubs and neighbors significantly influenced the transition probability of regions to clubs with high and low CO2 emissions. Therefore, if a province had a neighbor with low (high) CO2 emissions intensity, the transition probability of this province to the club with low (high) CO2 intensity increased. Therefore, in provinces that have neighbors with low (high) CO2 emissions intensity, the transition probability to the club with low (high) CO2 intensity increases.
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Dióxido de Carbono , Combustíveis Fósseis , Dióxido de Carbono/análise , Mudança Climática , Desenvolvimento Econômico , Política Ambiental , Irã (Geográfico)RESUMO
Ischemic stroke is characterized by extensive neuronal loss, glial scar formation, neural tissue degeneration that leading to profound changes in the extracellular matrix, neuronal circuitry, and long-lasting functional disabilities. Although transplanted neural stem cells (NSCs) can recover some of the functional deficit after stroke, retrieval is not complete and repair of lost tissue is negligible. Therefore, the current challenge is to use the combination of NSCs with suitably enriched biomaterials to retain these cells within the infarct cavity and accelerate the formation of a de novo tissue. This study aimed to test the regenerative potential of polylactic-co-glycolic acid-polyethylene glycol (PLGA-PEG) micelle biomaterial enriched with Reelin and embryonic NSCs on photothrombotic stroke model of mice to gain appropriate methods in tissue engineering. For this purpose, two sets of experiments, either in vitro or in vivo models, were performed. In vitro analyses exhibited PLGA-PEG plus Reelin-induced proliferation rate (Ki-67+ NSCs) and neurite outgrowth (axonization and dendritization) compared to PLGA-PEG + NSCs and Reelin + NSCs groups (p < 0.05). Besides, neural differentiation (Map-2+ cells) was high in NSCs cultured in the presence of Reelin-loaded PLGA-PEG micelles (p < 0.05). Double immunofluorescence staining showed that Reelin-loaded PLGA-PEG micelles increased the number of migrating neural progenitor cells (DCX+ cells) and mature neurons (NeuN+ cells) around the lesion site compared to the groups received PLGA-PEG and Reelin alone after 1 month (p < 0.05). Immunohistochemistry results showed that the PLGA/PEG plus Reelin significantly decreased the astrocytic gliosis and increased local angiogenesis (vWF-positive cells) relative to the other groups. These changes led to the reduction of cavity size in the Reelin-loaded PLGA-PEG+NSCs group. Neurobehavioral tests indicated Reelin-loaded PLGA-PEG+NSCs promoted neurological outcome and functional recovery (p < 0.05). These results indicated that Reelin-loaded PLGA-PEG is capable of promoting NSCs dynamic growth, neuronal differentiation, and local angiogenesis following ischemic injury via providing a desirable microenvironment. These features can lead to neural tissue regeneration and functional recovery.
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The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2), that already appeared as a global pandemic. Presentation of the disease often includes upper respiratory symptoms like dry cough, dyspnea, chest pain, and rhinorrhea that can develop to respiratory failure, needing intubation. Furthermore, the occurrence of acute and subacute neurological manifestations such as stroke, encephalitis, headache, and seizures are frequently stated in patients with COVID-19. One of the reported neurological complications of severe COVID-19 is the demolition of the myelin sheath. Indeed, the complex immunological dysfunction provides a substrate for the development of demyelination. Nevertheless, few published reports in the literature describe demyelination in subjects with COVID-19. In this short narrative review, we discuss probable pathological mechanisms that may trigger demyelination in patients with SARS-CoV-2 infection and summarize the clinical evidence, confirming SARS-CoV-2 condition as a risk factor for the destruction of myelin.
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COVID-19/complicações , COVID-19/imunologia , Doenças Desmielinizantes/virologia , Humanos , SARS-CoV-2RESUMO
Investigating the energy intensity convergence in Iran, as a country with very high energy intensity in the world, is important in order to assess whether the government's energy policies were effective to reduce energy intensity and its externality effects. This research investigated the convergence of total energy intensity and energy carriers' consumption intensity in Iran and whether the energy intensity in the provinces with high energy intensity has been converged to the provinces with low energy intensity. To that end, the Markov chain method was used to investigate the convergence of total energy intensity and energy carriers' consumption intensity in Iranian provinces from 2002 to 2016. The results indicated that there was club convergence in total energy, natural gas, electricity, and oil consumption intensity. Therefore, provinces with similar levels of energy intensity (e.g., high energy intensity and low energy intensity) converged to a unique steady state.
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Eletricidade , Gás Natural , Irã (Geográfico) , Organizações , Projetos de PesquisaRESUMO
Despite the poor regenerative capacity of the adult central nervous system (CNS) in mammals, two distinct regions, subventricular zone (SVZ) and the subgranular zone (SGZ), continue to generate new functional neurons throughout life which integrate into the pre-existing neuronal circuitry. This process is not fixed but highly modulated, revealing many intrinsic and extrinsic mechanisms by which this performance can be optimized for a given environment. The capacity for self-renewal, proliferation, migration, and multi-lineage potency of neural stem cells (NSCs) underlines the necessity of controlling stem cell fate. In this context, the native and local microenvironment plays a critical role, and the application of this highly organized architecture in the CNS has been considered as a fundamental concept in the generation of new effective therapeutic strategies in tissue engineering approaches. The brain extracellular matrix (ECM) is composed of biomacromolecules, including glycosaminoglycans, proteoglycans, and glycoproteins that provide various biological actions through biophysical and biochemical signaling pathways. Herein, we review predominantly the structure and function of the mentioned ECM composition and their regulatory impact on multiple and diversity of biological functions, including neural regeneration, survival, migration, differentiation, and final destiny of NSCs.