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OBJECTIVE: Previously, we have successfully purified and synthesized viscolin, an agent derived from Viscum coloratum extract, which has shown significant potential in the treatment of stroke. Our study aimed to evaluate the neuroprotective effects of viscolin. METHODS: We first assessed the cytotoxicity of viscolin on primary neuronal cultures and determined its antioxidant and radical scavenging properties. Subsequently, we identified the optimal dose-response of viscolin in protecting against glutamate-induced neurotoxicity. RESULTS: Our results demonstrated that viscolin at a concentration of 10 µM effectively reduced neuronal cell death up to 6 hours after glutamate-induced neurotoxicity. Additionally, we investigated the therapeutic window of opportunity and the potential of viscolin in preventing necrotic and apoptotic damage in cultured neurons exposed to oxygen glucose deprivation-induced neurotoxicity. Our findings showed that viscolin treatment significantly reduced DNA breakage, prevented the release of cytochrome c from mitochondria to cytosol, increased the expression of anti-apoptotic protein Bcl-2, decreased the expression of pro-apoptotic protein Bax, and reduced the number of TUNEL-positive cells. Additionally, our in vivo investigation demonstrated a reduction in brain infarction following middle cerebral artery occlusion. CONCLUSION: Viscolin has potential utility as a therapeutic agent in the treatment of stroke.
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In posterior spine surgery, retractors exert pressure on paraspinal muscles, elevating intramuscular pressure and compromising blood flow, potentially causing muscle injury during ischemia-reperfusion. Ginkgo biloba extract (EGb 761), known for its antioxidant and free radical scavenging properties and its role in treating cerebrovascular diseases, is investigated for its protective effects against muscle ischemia-reperfusion injury in vitro and in vivo. Animals were randomly divided into the control group, receiving normal saline, and experimental groups, receiving varying doses of EGb761 (25/50/100/200 mg/kg). A 2-h hind limb tourniquet-induced ischemia was followed by reperfusion. Blood samples collected pre-ischemia and 24 h post-reperfusion, along with muscle tissue samples after 24 h, demonstrated that EGb761 at 1000 µg/mL effectively inhibited IL-6 and TNF-α secretion in RAW 264.7 cells without cytotoxicity. EGb761 significantly reduced nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and increased glutathione (GSH) levels compared to the control after 24 h. Muscle tissue sections revealed more severe damage in the control group, indicating EGb761's potential in mitigating inflammatory responses and oxidative stress during ischemia-reperfusion injury, effectively protecting against muscle damage.
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Anti-Inflamatórios , Antioxidantes , Ginkgo biloba , Membro Posterior , Músculo Esquelético , Extratos Vegetais , Traumatismo por Reperfusão , Animais , Ginkgo biloba/química , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Extratos Vegetais/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/irrigação sanguínea , Camundongos , Membro Posterior/irrigação sanguínea , Masculino , Ratos , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Interleucina-6/metabolismo , Ratos Sprague-Dawley , Extrato de GinkgoRESUMO
Prothymosin α (ProT), a highly acidic nuclear protein with multiple cellular functions, has shown potential neuroprotective properties attributed to its antinecrotic and antiapoptotic activities. The present study aimed to investigate the beneficial effect of ProT on neuroplasticity after ischemiareperfusion injury and elucidate its underlying mechanism of action. Primary cortical neurons were either treated with ProT or overexpressing ProT by gene transfection and exposed to oxygenglucose deprivation for 2 h in vitro. Immunofluorescence staining for ProT and MAP2 was performed to quantify ProT protein expression and assess neuronal arborization. Mice treated with vehicle or ProT (100 µg/kg) and ProT overexpression in transgenic mice received middle cerebral artery occlusion for 50 min to evaluate the effect of ProT on neuroplasticityassociated protein following ischemiareperfusion injury. The results demonstrated that in cultured neurons ProT significantly increased neurite lengths and the number of branches, accompanied by an upregulation mRNA level of brainderived neurotrophic factor. Furthermore, ProT administration improved the protein expressions of synaptosomalassociated protein, 25 kDa and postsynaptic density protein 95 after ischemicreperfusion injury in vivo. These findings suggested that ProT can potentially induce neuroplasticity effects following ischemiareperfusion injury.
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Traumatismo por Reperfusão , Timosina , Timosina/análogos & derivados , Camundongos , Animais , Camundongos Transgênicos , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Regulação para Cima , Timosina/genética , Timosina/farmacologia , Timosina/metabolismo , Traumatismo por Reperfusão/tratamento farmacológicoRESUMO
(1) Background: Inducing experimental stroke leads to biphasic immune responses, where the early activation of immune functions is followed by severe immunosuppression accompanied by spleen and thymus atrophy. Nicotinamide, a water-soluble B-group vitamin, is a known neuroprotectant against brain ischemia in animal models. We examined the effect of nicotinamide on the central and peripheral immune response in experimental stroke models. (2) Methods: Nicotinamide (500 mg/kg) or saline was intravenously administered to C57BL/6 mice during reperfusion after transiently occluding the middle cerebral artery or after LPS injection. On day 3, the animals were examined for behavioral performance and were then sacrificed to assess brain infarction, blood-brain barrier (BBB) integrity, and the composition of immune cells in the brain, thymus, spleen, and blood using flow cytometry. (3) Results: Nicotinamide reduced brain infarction and microglia/macrophage activation following MCAo (p < 0.05). Similarly, in LPS-injected mice, microglia/macrophage activation was decreased upon treatment with nicotinamide (p < 0.05), suggesting a direct inhibitory effect of nicotinamide on microglia/macrophage activation. Nicotinamide decreased the infiltration of neutrophils into the brain parenchyma and ameliorated Evans blue leakage (p < 0.05), suggesting that a decreased infiltration of neutrophils could, at least partially, be the result of a more integrated BBB structure following nicotinamide treatment. Our studies also revealed that administering nicotinamide led to retarded B-cell maturation in the spleen and subsequently decreased circulating B cells in the thymus and bloodstream (p < 0.05). (4) Conclusions: Cumulatively, nicotinamide decreased brain inflammation caused by ischemia-reperfusion injury, which was mediated by a direct anti-inflammatory effect of nicotinamide and an indirect protective effect on BBB integrity. Administering nicotinamide following brain ischemia resulted in a decrease in circulating B cells. This warrants attention with respect to future clinical applications.
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OBJECTIVES: Lithium has numerous neuroplastic and neuroprotective effects in patients with stroke. Here, we evaluated whether delayed and short-term lithium treatment reduces brain infarction volume and improves electrophysiological and neurobehavioral outcomes following long-term recovery after cerebral ischemia and the possible contributions of lithium-mediated mechanisms of neuroplasticity. METHODS: Male Sprague Dawley rats were subjected to right middle cerebral artery occlusion for 90 min, followed by 28 days of recovery. Lithium chloride (1 mEq/kg) or vehicle was administered via intraperitoneal infusion once per day at 24 h after reperfusion onset. Neurobehavioral outcomes and somatosensory evoked potentials (SSEPs) were examined before and 28 days after ischemia-reperfusion. Brain infarction was assessed using Nissl staining. Primary cortical neuron cultures were exposed to oxygen-glucose deprivation (OGD) and treated with 2 or 20 µM lithium for 24 or 48 h; subsequent brain-derived neurotrophic factor (BDNF), growth-associated protein-43 (GAP-43), postsynaptic density-95 (PSD-95), and synaptosomal-associated protein-25 (SNAP-25) levels were analyzed using western blotting. RESULTS: Compared to controls, lithium significantly reduced infarction volume in the ischemic brain and improved electrophysiological and neurobehavioral outcomes at 28 days post-insult. In cultured cortical neurons, BDNF, GAP-43, and PSD-95 expression were enhanced by 24- and 48-h treatment with lithium after OGD. CONCLUSION: Lithium upregulates BDNF, GAP-43, and PSD-95, which partly accounts for its improvement of neuroplasticity and provision of long-term neuroprotection in the ischemic brain.Abbreviations: BDNF: brain-derived neurotrophic factor; ECM: extracellular matrix; EDTA: ethylenediaminetetraacetic acid; GAP-43: growth-associated protein-43; GSK-3ß: glycogen synthase kinase-3ß; HBSS: Hank's balanced salt solution; LCBF: local cortical blood perfusion; LDF: laser-Doppler flowmetry; MCAO: middle cerebral artery occlusion; MMP: matrix metalloproteinase; NMDA: N-methyl-D-aspartate; NMDAR: N-methyl-D-aspartate receptor; OCT: optimal cutting temperature compound; OGD: oxygen-glucose deprivation; PSD-95: postsynaptic density-95; SDS: sodium dodecyl sulfate; SNAP-25: synaptosomal-associated protein-25; SSEP: somatosensory evoked potential.
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Isquemia Encefálica , Proteína 4 Homóloga a Disks-Large , Proteína GAP-43 , Lítio , Fármacos Neuroprotetores , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Ácido Edético , Proteína GAP-43/metabolismo , Glucose , Glicogênio Sintase Quinase 3 beta/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Lítio/farmacologia , Cloreto de Lítio/farmacologia , Masculino , N-Metilaspartato , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Oxigênio , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Dodecilsulfato de SódioRESUMO
OBJECTIVES: Lithium exerts a broad neuroprotective effect on the brain. This study examined whether lithium exerts therapeutic effects on stroke by restoring neural connections at the ischemic core of cortices post brain insult. METHODS: We treated rats with lithium or vehicle (saline) every 24 h for the first 72 h, starting at the beginning of reperfusion after inducing middle cerebral artery occlusion (MCAO) in rats. Somatosensory evoked potential (SSEP) recording and behavioral testing were employed to evaluate the beneficial effects of lithium treatment. To examine the effects of lithium-induced neuroplasticity, we evaluated the dendritic morphology in cortex pyramidal cells and the primary neuronal cell culture that underwent brain insults and oxygen and glucose deprivation (OGD), respectively. RESULTS: The results demonstrated that rats subjected to MCAO had prolonged N1 latency and a decreased N1/P1 amplitude at the ipsilateral cortex. Four doses of lithium reduced the brain infarction volume and enhanced the SSEP amplitude. The results of neurobehavioral tests demonstrated that lithium treatment improved sensory function, as demonstrated by improved 28-point clinical scale scores. In vitro study results showed that lithium treatment increased the dendritic lengths and branches of cultured neurons and reversed the suppressive effects of OGD. The in vivo study results indicated that lithium treatment increased cortical spine density in various layers and resulted in the development of the dendritic structure in the contralateral hemisphere. CONCLUSION: Our study confirmed that neuroplasticity in cortical neurons is crucial for lithium-induced brain function 50 recovery after brain ischemia.
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Córtex Cerebral/efeitos dos fármacos , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Infarto da Artéria Cerebral Média/complicações , AVC Isquêmico/complicações , Compostos de Lítio/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Células Piramidais/efeitos dos fármacos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Células Cultivadas , Modelos Animais de Doenças , Compostos de Lítio/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , RatosRESUMO
BACKGROUND: Temozolomide (TMZ) has been widely used to treat glioblastoma multiforme (GBM). However, many mechanisms are known to quickly adapt GBM cells to chemotherapy with TMZ, leading to drug resistance and expansion of tumor cell populations. METHODS: We subjected human glioblastoma cell lines and an animal model of glioblastoma xenografts with TMZ-based adjuvant treatments to evaluate the synergistic effect of cinnamophilin (CINN), a free radical scavenger. RESULTS: Our results showed that the combined treatment of CINN and TMZ potentiated the anticancer effect and apoptotic cell death in glioma cell lines and enhanced antitumor action in glioma xenografts. TMZ induced reactive oxygen species (ROS) burst and elevated G2 arrest in glioma cells. The CINN-suppressed ROS burst in TMZ-treated glioma cells might be associated with increased apoptosis, as indicated by the upregulation of TUNEL-positive glioma cells. CINN-pretreated glioma cells exhibited increased cyclin B expression and reduced phosphorylation of Cdk1, suggesting reduced G2 arrest in the combined treatment group. Moreover, CINN lowered the protein level of LC3, a hallmark of autophagy, in TMZ-treated cells. CONCLUSIONS: These findings suggest that CINN may restore TMZ toxicity in glioma cancer by suppressing the ROS/G2 arrest pathway.
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Objective Atlantoaxial fixation is technically demanding and challenging, especially in cases with anatomical abnormality. The purpose of this study is to report the effectiveness of the three-dimensional (3D)-customized guiding template for placement of C1 and C2 screws in cases with abnormalities. Method Two patients with anatomical abnormality and one without were included. The preoperative computed tomography (CT) image was analyzed using our software. The entry point, trajectory, and depth of the screws were designed based on these images. Templates with screw guiding cylinders and cervical spine model were created. In operation, guiding templates were applied directly to the laminae. Drilling, tapping, and screwing were performed through the cylinders. To evaluate the accuracy, deviation of the screw axis from the preplanned trajectory was measured on postoperative CT. A classification system was taking to evaluate the pedicle screw insertion. Results In complex cases, one of C2 screws has grade 2 deviation, and two has grade 1. There was no deviation in screws of C1. All patients achieved symptoms free after 6 months follow-up. Conclusion Although 3D-printed template for atlantoaxial fixation still has limitation in complex cases, it has been proved usefulness and makes the most difficult and dangerous spinal posterior fixation easy to achieve.
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The Machilus genus (Lauraceae) had been extensively utilized in folk medicine due to its broad range of bioactivities. In the present study, a series of chromatographic separations of the methanol extract of stems of M. philippinensis led to the identification of thirty eight compounds totally. Among these, biscinnamophilin (1), machilupins A-C (2-4), machilutone A (5), and machilusoxide A (6) were new compounds reported for the first time. In addition, 5 was characterized with a unprecedented carbon skeleton. Other known compounds, including the major compounds cinnamophilin (7) and meso-dihydroguaiaretic acid (8), are identified by comparison of their physical and spectroscopic data with reported values. One of the reported compounds, cinnamophilin A (10), should be revised as dehydroguaiaretic acid (9) after careful comparison of all the 1H and 13C NMR data. Moreover, the neuroprotective activity of cinnamophilin (7) was examined in a primary cortical neuron culture and the results indicated that 7 was effective against glutamate induced excitotoxicity.
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3(5hydroxymethyl2furyl)1benzylindazole (YC1) is understood to protect against ischemic stroke, but the molecular basis for its neuroprotection remains to be fully characterized. The present study investigated the influence of YC1 on inflammatory responses following experimental stroke. Previous studies indicated that nuclear factor (NF)κBdriven signals serve a pivotal role in mediating inflammatory responses following stroke. Ischemic stroke results in activation of NFκB to induce gene expression of factors including inducible nitric oxide synthase, interleukin (IL)1ß, IL6 and matrix metalloproteinases (MMPs). The results of the present study demonstrated that YC1 effectively reduced brain infarction and brain edema, and improved bloodbrain barrier leakage. Additionally, animals treated with YC1 exhibited significant reductions in neutrophil and macrophage infiltration into the ischemic brain. Furthermore, YC1 effectively inhibited NFκB translocation and binding activity, and the activity and expression of MMP9 following ischemic stroke. In conclusion, YC1 may effectively attenuate NFκBinduced inflammatory damage following cerebral ischemiareperfusion.
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Edema Encefálico/metabolismo , NF-kappa B/metabolismo , Traumatismo por Reperfusão/metabolismo , Acidente Vascular Cerebral/metabolismo , Animais , Edema Encefálico/patologia , Isquemia Encefálica/patologia , Indazóis , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Acidente Vascular Cerebral/patologiaRESUMO
Endoplasmic reticulum (ER) stress plays a vital role in mediating ischemic reperfusion damage in brain. In this study, we evaluated whether melatonin inhibits ER stress in cultured neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to transient focal cerebral ischemia. Sprague-Dawley rats were treated with melatonin (5 mg/kg) or control at reperfusion onset after transient occlusion of the right middle cerebral artery (MCA) for 90 min. Brain infarction and hemorrhage within infarcts were measured. The expression of ER stress proteins of phosphorylation of PRKRlike endoplasmic reticulum kinase (p-PERK), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) were detected by western blotting and immunohistochemistry analysis. The terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) method, cleaved caspase-3 and cytochrome c were used to investigate cell apoptosis in OGD-induced cultured neurons. Our results demonstrated that animals treated with melatonin had significantly reduced infarction volumes and individual cortical lesion sizes as well as increased numbers of surviving neurons. Melatonin can significantly modulate protein levels by decreasing both p-PERK and p-eIF2α in the ischemic core and penumbra. Moreover, the expressions of ATF4 and CHOP were restrained in the ischemic core and penumbra, respectively. Furthermore, pretreatment with melatonin at 10-100 µM effectively reduced the levels of p-PERK and p-eIF2α in cultured neurons after OGD injury. Melatonin treatment also effectively decreased neuron apoptosis resulting from OGD-induced neuron injury. These results indicate that melatonin effectively attenuated post-ischemic ER stress after ischemic stroke.
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Encéfalo/patologia , Estresse do Retículo Endoplasmático , Melatonina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Fator 4 Ativador da Transcrição/metabolismo , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fator de Iniciação 2 em Eucariotos/metabolismo , Glucose/deficiência , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Sistema de Sinalização das MAP Quinases , Masculino , Melatonina/farmacologia , Modelos Biológicos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Oxigênio , Fosforilação , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Transdução de Sinais , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/metabolismoRESUMO
3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), has been demonstrated to inhibit platelet aggregation, vascular contraction and hypoxiainducible factor 1 activity in vitro and in vivo. The present study investigated the neuroprotective efficacy of YC1 in cultured neurons exposed to glutamateinduced excitotoxicity and in an animal model of stroke. In a cortical neuronal culture model, YC1 demonstrated neurotoxicity at a concentration >100 µM, and YC1 (1030 µM) achieved potent cytoprotection against glutamateinduced neuronal damage. Additionally, YC1 (30 µM) effectively attenuated the increase in intracellular Ca2+ levels. Delayed treatment of YC1 (30 µM) also protected against glutamateinduced neuronal damage and cell swelling in cultured neurons, though only at 4 h posttreatment. In addition, immediate treatment of YC1 (30 µM) following the exposure of cortical neurons to glutamate (300 µM) produced a marked reduction in intracellular pH. Delayed treatment of YC1 (25 mg/kg) protected against ischemic brain damage in vivo, though only when administered at 3 h postinsult. Thus, YC1 exhibited neuroprotection against glutamate-induced neuronal damage and in mice subjected to transient focal cerebral ischemia. This neuroprotection may be mediated via its ability to limit the glutamateinduced excitotoxicity. However, the neuroprotective therapeutic window of YC1 is only at 3 h in vivo and 4 h in vitro, which may, at least in part, be attributed to its ability to reduce the intracellular pH in the early phase of ischemic stroke. Although YC1 provided the potential for clinical therapy, the treatment time point must be carefully evaluated following ischemia.
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Isquemia Encefálica , Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Ácido Glutâmico/efeitos adversos , Indazóis/farmacologia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Animais , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Citoproteção/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Camundongos , Neurônios/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
In the present study, the neuroprotective potential of magnolol against ischemia-reperfusion brain injury was examined via in vivo and in vitro experiments. Magnolol exhibited strong radical scavenging and antioxidant activity, and significantly inhibited the production of interleukin6, tumor necrosis factora and nitrite/nitrate (NOX) in lipopolysaccharide-stimulated BV2 and RAW 264.7 cells when applied at concentrations of 10 and 50 µM, respectively. Magnolol (100 µM) also significantly attenuated oxygenglucose deprivationinduced damage in neonatal rat hippocampal slice cultures, when administered up to 4 h following the insult. In a rat model of stable ischemia, compared with a vehicletreated ischemic control, pretreatment with magnolol (0.011 mg/kg, intravenously) significantly reduced brain infarction following ischemic stroke, and posttreatment with magnolol (1 mg/kg) remained effective and significantly reduced infarction when administered 2 h following the onset of ischemia. Additionally, magnolol (0.3 and 1 mg/kg) significantly reduced the accumulation of superoxide anions at the border zones of infarction and reduced oxidative damage in the ischemic brain. This was assessed by measuring the levels of NOX, malondialdehyde and myeloperoxidase, the ratio of glutathione/oxidized glutathione and the immunoreactions of 8hydroxy2'deoxyguanosine and 4hydroxynonenal. Thus, magnolol was revealed to protect against ischemiareperfusion brain damage. This may be partly attributed to its antioxidant, radical scavenging and antiinflammatory effects.
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Antioxidantes/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Lignanas/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Linhagem Celular , Glucose/metabolismo , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/metabolismo , Células RAW 264.7 , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
As spine surgery flourished in Taiwan and neurosurgeons became more involved in spine surgery towards the end of the 20th century, the Taiwan Neurosurgical Spine Society (TNSS), earlier named the Taiwan Neurospinal Society, was established on March 11, 2001. As its main founder, Dr. Chun-I Huang was elected as the first president of the TNSS. The goals of the TNSS were to promote research, to hold academic seminars, to participate in international conferences, and to exchange clinical experiences. The mission of the TNSS was successful, and the profession of spine surgery in Taiwan advanced during the first decade of the 21st century, culminating in the TNSS joining ASIA SPINE in 2010. Since its establishment, the TNSS has always been supportive of collaboration and communication with the Korean Spinal Neurosurgery Society and the Neurospinal Society of Japan. Through periodical meetings, supported by the TNSS, surgeons worldwide have enjoyed a platform of sharing and mutual learning. To further promote academic research, the TNSS has officially supported the journal Neurospine since 2018. With extensive efforts from local and international surgeons, the TNSS will continue to adhere to its mission and to advance the profession of spine surgery.
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Objectives Focal cerebral ischemia may induce synaptic, electrophysiological, and metabolic dysfunction in remote areas. We have shown that the remote dendritic spine density changes and electrophysiological diaschisis in the acute and subacute stages after stroke previously. Here, we further evaluated electrophysiological outcomes and synapto-dendritic plasticity in long-term recovery in the contralateral cortex following focal cerebral ischemia. Methods Male Sprague-Dawley rats were subjected to intraluminal suture occlusion for 90 min or sham-occlusion. Somatosensory electrophysiological recordings (SSEPs) and neurobehavioral tests were recorded each day for 28 days. Postmortem brains were sectioned and subjected to Nissl staining and Golgi-Cox impregnation through a 28-day period following ischemic stroke. Results In the ipsilateral cortex, infarct size in the cortex and striatum was decreased after the subacute stage; the brains showed reduced swelling in the cortex and stratum 3 days after ischemic insults. Dendritic spine density and SSEP amplitude decreased significantly during a 28-day recovery period. In the contralateral cortex, dendritic spine density and SSEP amplitude decreased significantly for 21 days after ischemic stroke, but recovered to baseline by day 28. The deterioration of the dendritic spine (density reduction) in the ischemic cortex was observed; however, this increased neuroplasticity in the contralateral cortex in the subacute stage. Discussion Focal cerebral ischemia-reperfusion induces time-dependent reduction of dendritic spine density and electrophysiological depression in both the ipsilateral and contralateral cortices and intact brain. This neuroanatomical and electrophysiological evidence suggests that neuroplasticity and functional re-organization in the contralateral cortex is possible following focal cerebral ischemia.
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Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Lateralidade Funcional , Ataque Isquêmico Transitório/patologia , Ataque Isquêmico Transitório/fisiopatologia , Recuperação de Função Fisiológica , Animais , Corpo Estriado/patologia , Corpo Estriado/fisiopatologia , Espinhas Dendríticas/patologia , Espinhas Dendríticas/fisiologia , Modelos Animais de Doenças , Potenciais Somatossensoriais Evocados , Masculino , Plasticidade Neuronal/fisiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologiaRESUMO
Four A-type flavan-3-ol-dihydroretrochalcone dimers, dragonins A-D (1-4), were characterized from the traditional Chinese medicine Sanguis Draconis. The structures of 1-4 were elucidated by spectroscopic and spectrometric analyses. Compounds 1 and 2 exhibited significant inhibition of fMLP/CB-induced superoxide anion and elastase. The signaling pathways accounting for the inhibitory effects of compound 2 were also elucidated. These purified A-type flavan-3-ol-dihydroretrochalcones are new potential leads for the development of anti-inflammatory drugs.
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Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Chalconas/isolamento & purificação , Chalconas/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Resinas Vegetais/química , Anti-Inflamatórios/química , Chalconas/química , Flavonoides/química , Humanos , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Ressonância Magnética Nuclear Biomolecular , Elastase Pancreática/antagonistas & inibidores , Superóxidos/antagonistas & inibidoresRESUMO
Fifty compounds were isolated from the fruits of Forsythia suspensa, including 13 new compounds characterized as eight new diterpenoids (1-8), three new lignans (9-11), a new iridoid (12), and a new triterpenoid (13). Their structures were established on the basis of spectroscopic and spectrometric analysis. Most of the isolated compounds were examined for their anti-inflammatory activity in vitro. The results showed that several compounds displayed significant inhibition of fMLP/CB-induced superoxide anion generation and elastase release, with IC50 values ranging from 0.6 ± 0.1 to 8.6 ± 0.8 µg/mL and from 0.8 ± 0.3 to 7.3 ± 1.1 µg/mL, respectively.