72 research outputs found
Effects of low- and high-frequency repetitive magnetic stimulation on neuronal cell proliferation and growth factor expression: A preliminary report
No full textRepetitive magnetic stimulation is a neuropsychiatric and neurorehabilitation tool that can be used to investigate the neurobiology of sensory and motor functions. Few studies have examined the effects of repetitive magnetic stimulation on the modulation of neurotrophic/growth factors and neuronal cells in vitro. Therefore, the current study examined the differential effects of repetitive magnetic stimulation on neuronal cell proliferation as well as various growth factor expression. Immortalized mouse neuroblastoma cells were used as the cell model in this study. Dishes of cultured cells were randomly divided into control, sham, low-frequency (0.5Hz, 1Tesla) and high-frequency (10Hz, 1Tesla) groups (n=4 dishes/group) and were stimulated for 3 days. Expression of neurotrophic/growth factors, Akt and Erk was investigated by Western blotting analysis 3 days after repetitive magnetic stimulation. Neuroblastoma cell proliferation was determined with a cell counting assay. There were differences in cell proliferation based on stimulus frequency. Low-frequency stimulation did not alter proliferation relative to the control, while high-frequency stimulation elevated proliferation relative to the control group. The expression levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3) and platelet-derived growth factor (PDGF) were elevated in the high-frequency magnetic stimulation group. Akt and Erk expression was also significantly elevated in the high-frequency stimulation group, while low-frequency stimulation decreased the expression of Akt and Erk compared to the control. In conclusion, we determined that different frequency magnetic stimulation had an influence on neuronal cell proliferation via regulation of Akt and ERK signaling pathways and the expression of growth factors such as BDNF, GDNF, NT-3 and PDGF. These findings represent a promising opportunity to gain insight into how different frequencies of repetitive magnetic stimulation may mediate cell proliferation.ope
Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury
No full textPolydeoxyribonucleotide (PDRN) is an agonist that selectively stimulates adenosine A2A receptor (ADORA2A), which suppresses inflammatory responses. Ischemia/reperfusion (I/R) injury plays a major role in the pathogenesis of ischemic stroke by inducing neuroinflammation. Therefore, this study aimed to investigate the therapeutic effects of PDRN in an in vitro I/R injury model. The in vitro model was established with differentiated Neuro-2a cells under oxygen and glucose deprivation condition. The cells were treated with PDRN for 24 h under reoxygenation condition. As the results of RNA-seq transcriptome analysis, CSF1, IL-6, PTPN6, RAC2, and STAT1 were identified of its relation to the effect of PDRN on inflammatory responses in the model. To further investigate therapeutic effects of PDRN, RT-qPCR, western blotting, LDH assay, and TUNEL assay were performed. PDRN significantly reversed the expression of genes and proteins related to inflammatory responses. The elevated ADORA2A expression by PDRN treatment downregulated JAK/STAT pathway in the model. Furthermore, PDRN inhibited neuronal cell death in the model. Consequently, our results suggested that PDRN alleviated inflammatory responses through inhibition of JAK/STAT pathway by mediating ADORA2A expression and inhibited neuronal cell death in the model. These results provide significant insights into potential therapeutic approaches involving PDRN treatment for I/R injury. © 2023. The Author(s).ope
Three-dimensional brain-like microenvironments facilitate the direct reprogramming of fibroblasts into therapeutic neurons
No full textBiophysical cues can improve the direct reprogramming of fibroblasts into neurons that can be used for therapeutic purposes. However, the effects of a three-dimensional (3D) environment on direct neuronal reprogramming remain unexplored. Here, we show that brain extracellular matrix (BEM) decellularized from human brain tissue facilitates the plasmid-transfection-based direct conversion of primary mouse embryonic fibroblasts into induced neuronal (iN) cells. We first show that two-dimensional (2D) surfaces modified with BEM significantly increase the generation efficiency of iN cells and enhance neuronal transdifferentiation and maturation. Moreover, in an animal model of ischaemic stroke, iN cells generated on the BEM substrates and transplanted into the brain led to significant improvements in locomotive behaviours. We also show that compared with the 2D BEM substrates, 3D BEM hydrogels recapitulating brain-like microenvironments further promote neuronal conversion and potentiate the functional recovery of the animals. Our findings suggest that 3D microenvironments can boost nonviral direct reprogramming for the generation of therapeutic neuronal cells. © 2018 The Author(s
Therapeutic effects of repetitive transcranial magnetic stimulation in an animal model of Parkinson's disease
No full textRepetitive transcranial magnetic stimulation (rTMS) is used to treat neurological diseases such as stroke and Parkinson's disease (PD). Although rTMS has been used clinically, its underlying therapeutic mechanism remains unclear. The objective of the present study was to clarify the neuroprotective effect and therapeutic mechanism of rTMS in an animal model of PD. Adult Sprague-Dawley rats were unilaterally injected with 6-hydroxydopamine (6-OHDA) into the right striatum. Rats with PD were then treated with rTMS (circular coil, 10 Hz, 20 min/day) daily for 4 weeks. Behavioral assessments such as amphetamine-induced rotational test and treadmill locomotion test were performed, and the dopaminergic (DA) neurons of substantia nigra pas compacta (SNc) and striatum were histologically examined. Expression of neurotrophic/growth factors was also investigated by multiplex ELISA, western blotting analysis and immunohistochemistry 4 weeks after rTMS application. Among the results, the number of amphetamine-induced rotations was significantly lower in the rTMS group than in the control group at 4 weeks post-treatment. Treadmill locomotion was also significantly improved in the rTMS-treated rats. Tyrosine hydroxylase-positive DA neurons and DA fibers in rTMS group rats were greater than those in untreated group in both ipsilateral SNc and striatum, respectively. The expression levels of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, platelet-derived growth factor, and vascular endothelial growth factor were elevated in both the 6-OHDA-injected hemisphere and the SNc of the rTMS-treated rats. In conclusion, rTMS treatment improved motor functions and survival of DA neurons, suggesting that the neuroprotective effect of rTMS treatment might be induced by upregulation of neurotrophic/growth factors in the PD animal model.ope
Reducing ammonia volatilization in rice paddy: the importance of lower fertilizer rates and soil incorporation
No full textIn rice paddies, which exhibit higher ammonia (NH₃) emission factors than upland soils, identifying key drivers of NH₃ flux intensity is crucial. Contrary to the commonly held view that NH₃ flux is primarily governed by soil ammonium (NH₄⁺) concentrations, we found no significant relationship between NH₃ flux and NH₄⁺ levels in the soil during rice cultivation. To pinpoint a primary factor influencing NH₃ flux intensity under conventional rice cropping practices, we conducted a 2-year field study applying four nitrogen (N) fertilization rates (0, 45, 90, and 180 kg N ha⁻¹) using urea [(NH₂)₂CO], the most common N fertilizer. NH₃ emissions were tracked using the ventilation method. Following N application, NH₃ flux sharply increased but rapidly returned to baseline. Half of the N applied as a basal fertilizer was incorporated within the soil, contributing only 10% of total NH₃ emissions. In contrast, top-dressed applications—20% of total N at the tillering stage and 30% at panicle initiation—accounted for approximately 90% of NH₃ loss. Seasonal NH₃ flux increased quadratically with rising N application rates, correlating strongly with NH₄⁺ concentrations in floodwater rather than soil. Grain yield responded quadratically to N levels, peaking at 120 kg N ha⁻¹ with a 37% increase over control yields. NH₃ flux intensity, defined as seasonal NH₃ flux per unit of grain yield, showed a quadratic response to N fertilization, decreasing with initial fertilizer additions (up to 38 kg N ha⁻¹) but then sharply increased with further N fertilization increase. Hence, reducing NH₄⁺ concentrations in floodwater through moderated N application and deeper fertilizer placement could be essential for minimizing NH₃ volatilization in rice systems
Uncertainty of methane emissions coming from the physical volume of plant biomass inside the closed chamber was negligible during cropping period.
No full textIn rice paddy, the closed chamber method is broadly used to estimate methane (CH4) emission rate. Since rice plants can significantly affect CH4 production, oxidation and emission, rice plantation inside the chamber is standardized in IPCC guidelines. Methane emission rate is calculated using the increased concentration inside the headspace. Biomass growth might decrease the headspace volume, and thus CH4 emission rates might be overestimated. To evaluate the influence of chamber headspace decreased by rice plant development on CH4 emission rates, five Korean rice cultivars were cultivated in a typical rice paddy, and physical volume changes in rice biomass were assayed using water displacement method. The recommended acrylic closed chambers (H. 1.2 m x W. 0.6 m x L. 0.6 m) were installed, and eight rice plants were transplanted inside the chamber with the same space interval with the outside. Biomass growth significantly decreased the headspace volume of the chamber. However, this volume covered only 0.48-0.55% of the closed chamber volume at the maximum growth stage. During the whole cropping period, mean 0.24-0.28% of chamber headspace was allocated by plant biomass, and thus this level of total CH4 emissions was overestimated. However, this overestimation was much smaller than the errors coming from other investigation processes (i.e., chamber closing hour, temperature recording, inconstant flooding level, different soil environments, etc.) and rice physiological changes. In conclusion, the influence of physical biomass volume inside the closed chamber was negligible to make the error in total CH4 emission assessment in rice paddies
Effects of low- and high-frequency repetitive magnetic stimulation on neuronal cell proliferation and growth factor expression: A preliminary report
No full textAbstractRepetitive magnetic stimulation is a neuropsychiatric and neurorehabilitation tool that can be used to investigate the neurobiology of sensory and motor functions. Few studies have examined the effects of repetitive magnetic stimulation on the modulation of neurotrophic/growth factors and neuronal cells in vitro. Therefore, the current study examined the differential effects of repetitive magnetic stimulation on neuronal cell proliferation as well as various growth factor expression. Immortalized mouse neuroblastoma cells were used as the cell model in this study. Dishes of cultured cells were randomly divided into control, sham, low-frequency (0.5Hz, 1Tesla) and high-frequency (10Hz, 1Tesla) groups (n=4 dishes/group) and were stimulated for 3 days. Expression of neurotrophic/growth factors, Akt and Erk was investigated by Western blotting analysis 3 days after repetitive magnetic stimulation. Neuroblastoma cell proliferation was determined with a cell counting assay. There were differences in cell proliferation based on stimulus frequency. Low-frequency stimulation did not alter proliferation relative to the control, while high-frequency stimulation elevated proliferation relative to the control group. The expression levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3) and platelet-derived growth factor (PDGF) were elevated in the high-frequency magnetic stimulation group. Akt and Erk expression was also significantly elevated in the high-frequency stimulation group, while low-frequency stimulation decreased the expression of Akt and Erk compared to the control. In conclusion, we determined that different frequency magnetic stimulation had an influence on neuronal cell proliferation via regulation of Akt and ERK signaling pathways and the expression of growth factors such as BDNF, GDNF, NT-3 and PDGF. These findings represent a promising opportunity to gain insight into how different frequencies of repetitive magnetic stimulation may mediate cell proliferation
The effect of intracoronary nicorandil on coronary myocardial bridging
No full textMedical treatments of coronary myocardial bridging (CMB) generally include beta-blockers and calcium channel blockers. Nitrates are avoided because symptoms may worsen. Nicorandil is a hybrid of a nitrate and a potassium channel opener. However, the effect of nicorandil on CMB is unknown. We analyzed nicorandil reactivity at the site with CMB in 51 patients. Maximal and minimal diameters of CMB were measured by quantitative angiography at baseline and at 60 seconds after intracoronary administration of 200 mg nicorandil. The maximal diameter during diastole increased from 2.15 + 0.42 mm to 2.34 + 0.44 mm after administration of nicorandil (P < .001), and the minimal diameter during systole increased from 1.24 + 0.63 mm to 1.67 + 0.64 mm (P < .001). Thus, nicorandil reduced the percentage vessel narrowing from 44.0 + 26.1% to 30.3 + 21.2% (P < .001). In 22 patients, we also evaluated the effect of nitroglycerin. The maximal diameter during diastole increased from 2.25 + 0.47 mm to 2.51 + 0.44 mm after administration of nitroglycerin (P < .019), and the minimal diameter during systole decreased from 1.28 + 0.64 mm to 1.14 + 0.60 mm (P = .276). Thus, nitroglycerin augmented the percentage vessel narrowing from 44.9% + 25.0% to 56.0% + 23.5% (P = .023). These results indicate that intracoronary administration of nicorandil could dilate coronary arteries during diastole as well as systole in patients with CMB during coronary angiography.ope
Clopidogrel pretreatment before primary percutaneous coronary stenting in patients with acute ST-segment elevation myocardial infarction: comparison of high loading dose (600 mg) versus low loading dose (300 mg)
No full textBACKGROUND: Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardiac events after coronary intervention. As compared with the conventional 300-mg dose, pretreatment with a 600-mg loading dose of clopidogrel significantly reduced periprocedural myocardial infarction (MI) in patients undergoing percutaneous coronary intervention (PCI). We investigated that the advantage of the 600-mg dose in inhibiting platelet aggregation more rapidly than the 300-mg dose may actually have special value for acute ST-segment elevation MI patients.
METHODS: A total of 171 patients with ST-segment elevation MI underwent primary PCI. A 600-mg (n=73) or 300-mg (n=98) loading regimen of clopidogrel was given before the procedure. We did a follow-up of all patients clinically for 30 days after coronary intervention. the primary endpoint was the 30-day occurrence of death, MI, urgent revascularization, or stroke.
RESULTS: the primary endpoint occurred in 1.4% (1 of 73) of patients in the high dose versus 11.2% (11 of 98) of those in the conventional loading dose group (P=0.013). Death, recurrent MI, urgent revascularization, and stroke were lower in patients treated with the high dose of clopidogrel compared with conventional dose. Safety endpoints were similar in the two groups.
CONCLUSION: Pretreatment with a 600-mg loading dose of clopidogrel before the procedure is safe and, as compared with the conventional 300-mg dose, significantly reduces recurrent MI and urgent revascularization in patients with primary PCI.ope
Spatial Distribution of Glucose Hypometabolism Induced by Intracerebroventricular Streptozotocin in Monkeys
No full textIntracerebroventricular injection of streptozotocin (icv-STZ) in rodents induces cellular and behavioral features mimicking Alzheimer's disease (AD). However, the effect of icv-STZ in terms of regional cerebral glucose metabolism has not yet been examined in vivo. Given that regionally specific hypometabolism of glucose is a consistent neuroimaging marker in early AD, we monitored 18F-deoxyglucose uptake using a high-resolution micro-PET after icv-STZ in non-human primates. Two cynomolgus monkeys (Macaca fascicularis) received STZ (2 mg/kg), and another two were given normal saline as controls, at the cerebellomedullary cistern (CM) three times (day 1, 7, and 14). FDG-PET, as well as MRI for structural evaluation, was performed immediately before, six weeks after, and 12 weeks after the first icv injection. In the STZ group, FDG uptake decreased significantly in comparison to the pre-injection baseline, at the precuneus, the posterior cingulate, and medial temporal cortices. Increase in sulcal markings suggesting brain atrophy was observed by MRI at six weeks post-injection. The structural changes normalized at 12 weeks, but the reduced FDG uptake persisted at the same loci. The cortical distribution of glucose hypometabolism was similar to that at early stages of AD patients. The findings demonstrate that the effect of icv-STZ is regionally specific, lending further support for the method as a model of AD pathogenesis. [ABSTRACT FROM AUTHOR]Copyright of Journal of Alzheimer's Disease is the property of IOS Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)This research was supported by The Original Technology Research Program for Brain Science through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology, Republic of Korea (2009-0080348 & 2009-0080357)
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