RESUMO
Previous studies showed that the onset age of second language acquisition (AoA-L2) can modulate brain structure of bilinguals. However, the underlying mechanism of anatomical plasticity induced by AoA-L2 is still a question in debate. In order to explore the issue, we recruited two groups of native Cantonese-Mandarin speakers, the early group began to speak in Mandarin at about 3.5 and the late group at about 6.5 years old. In addition, the early group had earlier experience in reading Chinese characters than the late group did. Through estimating the cortical thickness (CT), we found that (1) compared with the late group, the early group had thicker CT in the lateral occipital region, left middle temporal gyrus, and left parahippocampal region, which are all involved in visuospatial processing, probably reflecting the effect induced by the earlier or later experiences in processing the characters of Chinese for the two groups; and (2) compared with the late group, the early group had thicker CT in left superior parietal region, which is believed to be involved in language switching, maybe for the early group had the earlier experience in switching back and forth between Cantonese and Mandarin and therefore recruited the executive control network earlier. Our findings revealed the effects of the AoA-L2 in oral language acquisition as well as in written language acquisition as the main determinants of bilingual language structural representation in human brain.
Assuntos
Multilinguismo , Encéfalo , Mapeamento Encefálico , Criança , Humanos , Idioma , Desenvolvimento da LinguagemRESUMO
Notoginsenoside R1 (NGR1) is a predominant phytoestrogen extracted from Panax notoginseng that has recently been reported to play important roles in the treatment of cardiac dysfunction, diabetic kidney disease, and acute liver failure. Studies have suggested that NGR1 may be a viable treatment of hypoxic-ischemic brain damage (HIBD) in neonates by reducing endoplasmic reticulum stress via estrogen receptors (ERs). However, whether NGR1 has other neuroprotective mechanisms or long-term neuroprotective effects is unclear. In this study, oxygen-glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons and unilateral ligation of the common carotid artery (CCL) in 7-day-old postnatal Sprague Dawley (SD) rats followed by exposure to a hypoxic environment were used to mimic an HIBD episode. We assessed the efficacy of NGR1 by measuring neuronal damage with MTT assay and assessed brain injury by TTC staining and brain water content detection 24-48 h after OGD/HIE. Simultaneously, we measured the long-term neurophysiological effects using the beam walking test (5 weeks after HI) and Morris water maze test 5-6 weeks after HI. Expression of PI3K-Akt-mTOR/JNK (24 h after HI or OGD/R) proteins was detected by Western blotting after stimulation with HI, NGR1, LY294002 (PI3K inhibitor), 740Y-P (PI3K agonist), or ICI 182780(estrogen receptors inhibitor). The results indicated that NGR1 exerted neuroprotective effects by inhibiting neuronal apoptosis and promoting cell survival via the PI3K-Akt-mTOR/JNK signaling pathways by targeting ER in neonatal hypoxic-ischemic injury.
Assuntos
Ginsenosídeos/uso terapêutico , Hipóxia-Isquemia Encefálica/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Fármacos Neuroprotetores/uso terapêutico , Fosfatidilinositol 3-Quinases/biossíntese , Proteínas Proto-Oncogênicas c-akt/biossíntese , Serina-Treonina Quinases TOR/biossíntese , Animais , Animais Recém-Nascidos , Células Cultivadas , Ginsenosídeos/farmacologia , Hipóxia-Isquemia Encefálica/prevenção & controle , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Notoginsenoside R1 (NGR1) is a phytoestrogen that is isolated from Panax notoginseng It is used in China to treat many diseases, including hypoxic-ischemic encephalopathy (HIE), and it has been shown to target estrogen receptors. Endoplasmic reticulum (ER) stress plays an important role in the development of cell apoptosis during ischemia, and ER stress is known to be regulated by estrogen; however, the neuroprotective mechanisms of NGR1 in neonatal HIE is unclear. In this study, oxygen-glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons and unilateral ligation of the common carotid artery (CCL), followed by exposure to a hypoxic environment in 7-day-old postnatal Sprague-Dawley rats were used to mimic HIE episodes. Potential neuroprotective effects of NGR1 against neonatal HIE and its mechanisms were examined. After HIE conditions in vitro and in vivo, we administered NGR1 or the estrogen receptor inhibitor ICI-182780 and measured cell apoptosis, brain injury by MTT assay, TTC stain, and so forth. Expression of estrogen receptors α (ERα) and ß (ERß), ER stress-associated proteins was detected by Western blot upon stimulation with HIE, NGR1, or ICI-182780. Results showed that after HIE, ER chaperone GRP78 was activated, ER stress-associated proapoptotic proteins (CHOP, PERK, ERO1-α, and IRE1α) were increased, caspase-12 was increased, and BCL-2 was decreased. The ER stress response and neuronal apoptosis were attenuated by NGR1 treatment. However, neuroprotective properties of NGR1 against HIE-induced apoptosis and ER stress were attenuated by ICI-182780. These results suggest that NGR1 may be an effective treatment of HIE by reducing ER stress-induced neuronal apoptosis and brain injury via estrogen receptors.
Assuntos
Citoproteção/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ginsenosídeos/farmacologia , Hipóxia-Isquemia Encefálica/patologia , Fármacos Neuroprotetores/farmacologia , Receptores de Estrogênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Artéria Carótida Primitiva/efeitos dos fármacos , Artéria Carótida Primitiva/patologia , Regulação para Baixo/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Sprague-DawleyRESUMO
An SHS-CFSHS X-joint is fabricated by welding two square hollow section (SHS) braces to a concrete-filled square hollow section (CFSHS) chord. In this paper, the stress concentration factors (SCFs) of SHS-CFSHS X-joints are investigated through experimental tests and finite element analysis (FEA), with the hot spot stress method serving as the analytical approach. Eight specimens are designed and manufactured, with FE models built in software ANSYS. These FE models are validated against the test results. The specimens are tested under brace axial tension to determine the SCFs of the X-joints. It shows that the concrete filled in the chord effectively reduces the SCFs of the X-joints. To further explore various load conditions and the influence of the parameters, FEA is carried out and a total of 64 FE models are built. Based on the FEA results, multiple regression analysis is used to obtain the SCF formulae of SHS-CFSHS X-joints under axial tension load and in-plane bending load in the brace, respectively. Comparison and analysis of the SCF results obtained from experimental tests, the proposed formulae, and FE simulations reveal that the formulae presented in this study are both conservative and suitable for predicting SCFs.
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The hydroxycamptothecin (HCPT) PEGylated liposomes (HCPT-LP) were modified with RGD cyclopeptide formed the tumor-targeting liposomes (HCPT-RGD-LP). HCPT-LP and HCPT-RGD-LP were injected intravenously with single dose of 5 mg x kg(-1) to rats. The drug concentration in plasma was determined and the pharmacokinetic behaviour was compared. The HCPT distribution in heart, liver, spleen, lung, kidney and plasma of mice was investigated following intravenous administration of HCPT-LP and HCPT injection. The nude mice implanted human hepatoma HepG2 cells were studied by in vivo imaging. The fluorescent probe was DiR and the nude mice were injected with DiR PEGylated liposomes (DiR-LP) and DiR-LP modified with RGD cyclopeptide (DiR-RGD-LP). The results showed that there was no significant difference (P > 0.05) of main pharmacokinetic parameters t1/2beta, CL, V(c), AUC(0-48 h), AUC(0-inifinity), MRT(0-48 h), MRT(0-infinity) between HCPT-RGD-LP and HCPT-LP. HCPT-LP had a remarkably better long-circulating effect than HCPT injection in mice and the concentration of HCPT was highest in liver. The DiR accumulation in tumors of DiR-RGD-LP was higher than that of DiR-LP by the visualized fluorescence of in vivo imaging. It indicated that such PEGylated liposomes modified with RGD cyclopeptide could improve the tumor targeting efficacy.
Assuntos
Camptotecina/análogos & derivados , Sistemas de Liberação de Medicamentos , Lipossomos/farmacocinética , Oligopeptídeos/farmacocinética , Polietilenoglicóis/farmacocinética , Animais , Área Sob a Curva , Camptotecina/administração & dosagem , Camptotecina/química , Camptotecina/farmacocinética , Diagnóstico por Imagem , Feminino , Corantes Fluorescentes , Células Hep G2 , Humanos , Lipossomos/administração & dosagem , Lipossomos/química , Neoplasias Hepáticas/diagnóstico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Oligopeptídeos/administração & dosagem , Oligopeptídeos/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espectroscopia de Luz Próxima ao Infravermelho , Distribuição TecidualRESUMO
OBJECTIVE: To observe the effect of Rg1-induced NSCs in treatment of neonatal rat model with hypoxiaischemia. METHOD: The neonatal rat model of HIE was established and assessed by using TTC staining and behavioral observation, then Rg1-induced NSCs was transplanted into the neonatal rat of HIE by lateral ventricle injection. Water maze test and somatosensory evoked potential were detected to observe brain function and the immunohistochemistry was done to assess growth and differentiation about transplanted NSCs a month after transplanted. RESULT: The transplantation of Rg1-induced NSCs could significantly shorten incubation period, swimming distance, exploration time of target quadrants of water maze test and incubation period and amplitude of somatosensory evoked potentials. Additionally, the concentrated expression appeared in the hippocampus and grew around the ischemic injury area in transplantation group. CONCLUSION: Transplantation of Rg1-induced NSCs play a better role in the treatment of neonatal HIE rats.
Assuntos
Ginsenosídeos/farmacologia , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/terapia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/transplante , Recuperação de Função Fisiológica/fisiologia , Animais , Diferenciação Celular/efeitos dos fármacos , Potenciais Evocados , Feminino , Hipocampo/patologia , Hipocampo/fisiopatologia , Hipóxia-Isquemia Encefálica/fisiopatologia , Masculino , Aprendizagem em Labirinto , Células-Tronco Neurais/citologia , Ratos , Ratos Sprague-DawleyRESUMO
It is interesting to explore the effects of second language (L2) acquisition on anatomical change in brain at different stages for the neural structural adaptations are dynamic. Short-term Chinese training effects on brain anatomical structures in alphabetic language speakers have been already studied. However, little is known about the adaptations of the gray matter induced by acquiring Chinese language for a relatively long learning period in adult alphabetic language speakers. To explore this issue, we recruited 38 Indian overseas students in China as our subjects. The learned group included 17 participants who had learned Mandarin Chinese for an average of 3.24 years and achieved intermediate Chinese language proficiency. The control group included 21 subjects who had no knowledge about Chinese. None of the participants had any experience in learning logographic and tonal language before Chinese learning. We found that (1) the learned group had significantly greater gray matter volume (GMV) in the left lingual gyrus (LG) compared with the control group; (2) the Chinese characters' reading accuracy was significantly and positively correlated to the GMV in the left LG and fusiform gyrus (FG) across the two groups; and (3) in the learned group, the duration of Chinese learning was significantly and positively correlated with the GMV in the left inferior frontal gyrus (IFG) after correction for multiple comparisons with small volume corrections. Our structural imaging findings are in line with the functional imaging studies reporting increased brain activation induced by Chinese acquisition in alphabetic language speakers. The regional gray matter changes reflected the additional requirements imposed by the more difficult processing of Chinese characters and tones. The present study also show that the biological bases of the adaptations induced by a relatively long period of Chinese learning were limited in the common areas for first and foreign language processing.
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Subarachnoid hemorrhage (SAH) is a devastating stroke subtype accounting for approximately 3 to 7% of cases each year. Despite its rarity among the various stroke types, SAH is still responsible for approximately 25% of all stroke fatalities. Although various preventative and therapeutic interventions have been explored for potential neuroprotection after SAH, a considerable percentage of patients still experience serious neurologic and/or cognitive impairments as a result of the primary hemorrhage and/or secondary brain damage that occurs. Z-ligustilide (LIG), the primary lipophilic component of the Chinese traditional medicine radix Angelica sinensis, has been shown to reduce ischemic brain injury via antiapoptotic pathways. Accordingly, in our study, we investigated the neuroprotective potential of LIG after experimental SAH in rats. Rats with SAH that was induced using the established double hemorrhage model were studied with and without LIG treatment. Mortality, neurobehavioral evaluation, brain water content, blood-brain barrier (BBB) permeability, and vasospasm assessment of the basilar artery were measured on days 3 and 7 after injury. Additional testing was done to evaluate for apoptosis using TdT-mediated dUTP-biotin nick end labeling staining as well as immunohistochemistry and Western blotting to identify key proapoptotic/survival proteins, i.e., p53, Bax, Bcl-2, and cleaved caspase-3. The results showed that LIG treatment reduced mortality, neurobehavioral deficits, brain edema, BBB permeability, and cerebral vasospasm. In addition, treatment reduced the number of apoptotic cells in the surrounding brain injury site, which accompanied a marked down-regulation of proapoptotic proteins, p53, and cleaved caspase-3. Our data suggest that LIG may be an effective therapeutic modality for SAH victims by altering apoptotic mechanisms.
Assuntos
4-Butirolactona/análogos & derivados , Angelica sinensis , Fármacos Neuroprotetores/uso terapêutico , Fitoterapia , Hemorragia Subaracnóidea/tratamento farmacológico , 4-Butirolactona/farmacologia , 4-Butirolactona/uso terapêutico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Marcação In Situ das Extremidades Cortadas , Masculino , Fármacos Neuroprotetores/farmacologia , Óleos de Plantas/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/mortalidade , Hemorragia Subaracnóidea/patologia , Vasoespasmo Intracraniano/tratamento farmacológico , Vasoespasmo Intracraniano/etiologiaRESUMO
OBJECTIVE: recent trials have shown Ginsenoside Rb1 (GRb1), an active component of a well known Chinese medicine Panax Ginseng, plays a significant role in improving the complications seen after an ischemic brain event. In the present study, we investigated the use of GRb1 as a treatment modality to reduce brain edema, reduce arterial vasospasm, and improve neurobehavioral function after subarachnoid hemorrhage-induced brain injury (SAH) in rats. METHOD: male Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned to three groups: (1) Sham group (n = 10), (2) Vehicle group (SAH + no treatment; n = 12); (3) Treatment group (SAH + GRb1 treatment at 20 mg/kg; n = 11). Subarachnoid hemorrhage was induced using the modified double hemorrhage model followed by treatment administration intravenously. Post-operative assessment included neurobehavioral testing using the spontaneous activity scoring system, brain water content, and histological examination of the basilar artery. RESULTS: post-operative findings indicated treatment with GRb1 had significantly reduced brain edema and improved neurobehavioral functioning. In addition, histological examination revealed a significant reduction in basilar artery vasospasm and lumen thickness with treatment. CONCLUSION: the results of the study suggest that GRb1 treatment reduces brain edema, improves neurobehavioral function, and blocks vasculature thickening and spasm after SAH in rats. Given the novelty of the study, further research will be needed to confirm the benefits of treatment and mechanisms behind neuroprotection.
Assuntos
Lesões Encefálicas/prevenção & controle , Ginsenosídeos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Panax/química , Análise de Variância , Animais , Artéria Basilar/patologia , Artéria Basilar/ultraestrutura , Edema Encefálico/etiologia , Edema Encefálico/prevenção & controle , Lesões Encefálicas/etiologia , Lesões Encefálicas/mortalidade , Modelos Animais de Doenças , Masculino , Microscopia Eletrônica de Transmissão/métodos , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Fatores de TempoRESUMO
Progranulin is a secreted glycoprotein expressed in neurons and microglial cells that is involved in maintaining physiological functions. Many studies have found that progranulin may play a protective role against ischemic brain injury, but little is known about how the expression level and cellular localization status of progranulin is regulated after hypoxia-ischemia. Research has confirmed that sortilin, encoded by SORT1, can bind with progranulin and deliver a mature secretory isoform of progranulin to lysosomes, and progranulin is then cleaved. In the present study, we aimed to figure out whether sortilin could affect the expression and cellular localization of progranulin and regulate cell apoptosis during hypoxia-ischemia. In this study, oxygen-glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons was used to mimic hypoxic-ischemic episodes. After OGD/R, the neuroprotective effects of progranulin against hypoxia-ischemia were examined, and primary cortical neurons were transduced with a SORT1 knockdown lentivirus to inhibit the expression of sortilin. The results showed that sortilin inhibition increased PGRN expression and alleviated cell injury induced by hypoxia-ischemia. Additionally, sortilin inhibition was associated with less PGRN localization in lysosomes. All of these findings suggest that sortilin can regulate the expression of PGRN, most likely by transporting it to lysosomes and affecting the cell injury in hypoxia-ischemia.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/farmacologia , Glucose/metabolismo , Oxigênio/metabolismo , Progranulinas/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Lisossomos/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológicoRESUMO
The brain representation of language in bilinguals is sculptured by several factors, such as age of acquisition (AoA) and proficiency level (PL) in second language. Although the effect of AoA-L2 on brain function and structure has been studied, little attention is devoted to dynamic properties of the language network and their differences between early and late bilinguals. In this study, we acquired resting-state fMRI data from early and late Cantonese (L1)-Mandarin (L2) bilinguals with high PLs of verbal fluency in both languages. We then analyzed dynamic functional connectivity (dFC) by using the sliding-windows approach, estimated the dFC states by using the k-means clustering algorithm, and calculated the dynamic topological properties of the language network for the early and late bilinguals. We detected four dFC states, State 1, State 2, State 3, and State 4, which may be related to phonetic processing, semantic processing, language control, and syntactic processing, respectively. Compared to the late bilinguals, the early bilinguals showed higher dFC between the inferior frontal area and the temporal area in State 1 and State 2, while higher dFC between the cerebellum and other regions in State 3. The early bilinguals showed a higher clustering coefficient and local and global efficiency in State 1 and State 3, but lower characteristic path length in State 1, than the late bilinguals. Together, these results suggested that AoA-L2 affects temporal neural activation and dynamic topological properties of the language network. These findings provide new information to understand the effect of experience of L2 acquisition on language network in bilinguals.
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Individuals with intracerebral hemorrhage (ICH) suffer varying degrees of neurological dysfunction as a result of neuronal apoptosis, and thus, maintenance of neuronal survival may be crucial to prevent ICH brain injury. Here, we report that the expression of transient receptor potential vanilloid 4 (TRPV4) was upregulated in mouse neurons after ICH. The selective TRPV4 agonist GSK1016790 A aggravated neuronal death whereas the TRPV4 antagonist HC-067047 promoted neuronal survival after ICH. We found that GSK1016790 A triggered Ca2+ signals that were amplified and propagated by Ca2+-induced Ca2+ release (CICR) from the endoplasmic reticulum (ER) in the neurons. ICH recruited inositol triphosphate receptors (IP3Rs) into the TRPV4 protein complex, which positively regulated the activity of TRPV4 channels. Excessive activation of TRPV4 channels destroyed Ca2+ homeostasis and induced ER unfolded protein response (UPR). Blocking TRPV4 receptors decreased UPR, inhibited the PERK-CHOP-Bcl-2 signaling pathway and increased neuron survival. Overall, these results suggested that overactivation of TRPV4 channels after ICH ledto the destruction of Ca2+ homeostasis, which in turn caused UPR and neural apoptosis. Inhibition of TRPV4 channels is a promising therapy to promote neurons recover, and to ameliorate disability after ICH.
Assuntos
Hemorragia Cerebral/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Apoptose/fisiologia , Lesões Encefálicas/metabolismo , Cálcio/metabolismo , Morte Celular/fisiologia , Sobrevivência Celular/fisiologia , Hemorragia Cerebral/patologia , Estresse do Retículo Endoplasmático/fisiologia , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Leucina/análogos & derivados , Leucina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfolinas/farmacologia , Neurônios/metabolismo , Pirróis/farmacologia , Sulfonamidas/farmacologia , Resposta a Proteínas não DobradasRESUMO
As documented in our previous study, notoginsenoside R1 (NGR1) can inhibit neuron apoptosis and the expression of endoplasmic reticulum (ER) stress-associated pro-apoptotic proteins in hypoxic-ischemic encephalopathy. Recent evidence indicates that the Phospholipase C (PLC)/inositol 1,4,5-trisphosphate receptor (IP3R) is important for the regulation of Ca2+ release in the ER. Ca2+ imbalance can stimulate ER stress, CAMKII, and cell apoptosis. The purpose of this study was to further investigate the neuroprotective effect of NGR1 and elucidate how NGR1 regulates ER stress and cell apoptosis in the oxygen-glucose deprivation/reoxygenation (OGD/R) model. Cells were exposed to NGR1 or the PLC activator m-3M3FBS. Then, IP3R- and IP3-induced Ca2+ release (IICR) and activation of the ER stress and CaMKII signal pathway were measured. The results showed that NGR1 inhibited IICR and strengthened the binding of GRP78 with PERK and IRE1. NGR1 also alleviated the activation of the CaMKII pathway. Pretreatment with m-3M3FBS attenuated the neuroprotective effect of NGR1; IICR was activated, activation of the ER stress and CaMKII pathway was increased, and more cells were injured. These results indicate that NGR1 may suppress activation of the PLC/IP3R pathway, subsequently inhibiting ER Ca2+ release, ER stress, and CaMKII and resulting in suppressed cell apoptosis.
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Sinalização do Cálcio , Ginsenosídeos/farmacologia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Animais , Apoptose , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Hipóxia Celular , Células Cultivadas , Retículo Endoplasmático/metabolismo , Glucose/deficiência , Proteínas de Choque Térmico/metabolismo , Proteínas de Membrana/metabolismo , Neurônios/efeitos dos fármacos , Oxigênio/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Fosfolipases Tipo C/metabolismo , eIF-2 Quinase/metabolismoRESUMO
Early second language (L2) experience influences the neural organization of L2 in neuro-plastic terms. Previous studies tried to reveal these plastic effects of age of second language acquisition (AoA-L2) and proficiency-level in L2 (PL-L2) on the neural basis of language processing in bilinguals. Although different activation patterns have been observed during language processing in early and late bilinguals by task-fMRI, few studies reported the effect of AoA-L2 and high PL-L2 on language network at resting state. In this study, we acquired resting-state fMRI (R-fMRI) data from 10 Cantonese (L1)-Mandarin (L2) early bilinguals (acquired L2: 3years old) and 11 late bilinguals (acquired L2: 6years old), and analyzed their topological properties of language networks after controlling the language daily exposure and usage as well as PL in L1 and L2. We found that early bilinguals had significantly a higher clustering coefficient, global and local efficiency, but significantly lower characteristic path length compared to late bilinguals. Modular analysis indicated that compared to late bilinguals, early bilinguals showed significantly stronger intra-modular functional connectivity in the semantic and phonetic modules, stronger inter-modular functional connectivity between the semantic and phonetic modules as well as between the phonetic and syntactic modules. Differences in global and local parameters may reflect different patterns of neuro-plasticity respectively for early and late bilinguals. These results suggested that different L2 experience influences topological properties of language network, even if late bilinguals achieve high PL-L2. Our findings may provide a new perspective of neural mechanisms related to early and late bilinguals.
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Encéfalo/fisiologia , Desenvolvimento da Linguagem , Multilinguismo , Adulto , Idade de Início , Mapeamento Encefálico , China/etnologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Fonética , Semântica , Adulto JovemRESUMO
Graphene oxide (GO) is an oxidized derivative of graphene used in biotechnology and medicine. The safety of GO is uncertain, so we evaluated its toxicity in male rats. Rat tail veins were injected with 2.5, 5, or 10 mg/kg GO for seven days and behavioral patterns, pathology, and tissue morphology were assessed. Data show that behaviors were not altered according to an open field test and a functional observational battery test, but histopathological analysis indicated that GO caused inflammation of the lung, liver, and spleen. GO also reduced cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL). No other organs were modified. Thus, high concentrations of GO are toxic for the lung, liver, and spleen, but the mechanism by which this occurs requires more study.
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Grafite/toxicidade , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Compostos Orgânicos/toxicidade , Óxidos/toxicidade , Baço/efeitos dos fármacos , Animais , Masculino , Oxirredução , Ratos , Ratos Sprague-DawleyRESUMO
Although several studies have shown that language exposure crucially influence the cerebral representation of bilinguals, the effects of short-term change of language exposure in daily life upon language control areas in bilinguals are less known. To explore this issue, we employed follow-up fMRI to investigate whether differential exposure induces neuroplastic changes in the language control network in high-proficient Cantonese (L1)-Mandarin (L2) early bilinguals. The same 10 subjects underwent twice BOLD-fMRI scans while performing a silent narration task which corresponded to two different language exposure conditions, CON-1 (L1/L2 usage percentage, 50%:50%) and CON-2 (L1/L2 usage percentage, 90%:10%). We report a strong effect of language exposure in areas related to language control for the less exposed language. Interestingly, these significant effects were present after only a 30-day period of differential language exposure. In detail, we reached the following results: (1) the interaction effect of language and language exposure condition was found significantly in the left pars opercularis (BA 44) and marginally in the left MFG (BA 9); (2) in CON-2, increases of activation values in L2 were found significantly in bilateral BA 46 and BA 9, in the left BA44, and marginally in the left caudate; and (3) in CON-2, we found a significant negative correlation between language exposure to L2 and the BOLD activation value specifically in the left ACC. These findings strongly support the hypothesis that even short periods of differential exposure to a given language may induce significant neuroplastic changes in areas responsible for language control. The language which a bilingual is less exposed to and is also less used will be in need of increased mental control as shown by the increased activity of language control areas.
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Encéfalo/fisiologia , Idioma , Multilinguismo , Plasticidade Neuronal/fisiologia , Adulto , Mapeamento Encefálico , Feminino , Seguimentos , Lateralidade Funcional/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
BACKGROUND: Thrombopoietin (TPO) protects against heart damages by doxorubicin-induced cardiomyopathy in animal models. We aimed to investigate the therapeutic efficacy of TPO for treatment of myocardial infarction (MI) in a rat model and explored the mechanisms in terms of the genome-wide transcriptional profile, TPO downstream protein signals, and bone marrow endothelial progenitor cells (EPCs). METHODS: Sprague-Dawley rats were divided into 3 groups: Sham-operated, MI (permanent ligation of the left coronary artery) and MI+TPO. Three doses of TPO were administered weekly for 2 weeks, and outcomes were assessed at 4 or 8 weeks post-injury. RESULTS AND CONCLUSIONS: TPO treatment significantly improved left ventricular function, hemodynamic parameters, myocardium morphology, neovascularization and infarct size. MI damage upregulated a large cohort of gene expressions in the infarct border zone, including those functioned in cytoskeleton organization, vascular and matrix remodeling, muscle development, cell cycling and ion transport. TPO treatment significantly reversed these modulations. While phosphorylation of janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) was modified in MI animals, TPO treatment regulated phosphorylation of STAT3 and extracellular signal-regulated kinases (ERK), and bone morphogenetic protein 1 (BMP1) protein level. TPO also increased EPC colonies in the bone marrow of MI animals. Our data showed that TPO alleviated damages of heart tissues from MI insults, possibly mediated by multi-factorial mechanisms including suppression of over-reacted ventricular remodeling, regulation of TPO downstream signals and mobilization of endothelial progenitor cells. TPO could be developed for treatment of cardiac damages.
Assuntos
Modelos Animais de Doenças , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Trombopoetina/uso terapêutico , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologia , Animais , Masculino , Infarto do Miocárdio/genética , Ratos , Ratos Sprague-Dawley , Trombopoetina/farmacologiaRESUMO
PURPOSE: Dexrazoxane (DZR), a clinically approved cation chelator, is effective in reducing doxorubicin (DOX)-induced heart damage, yet its cardioprotective mechanism is not fully understood. We aimed to investigate the effects of DZR on the activation of Akt and Erk 1/2 signals in a rat model of DOX-induced cardiomyopathy. METHODS: Male Sprague-Dawley rats received weekly DOX injection (2.5 mg/kg) for 6 weeks, with or without DZR pretreatment at a dose ratio of 20:1. The ventricular functions of these animals were monitored at week 6, 9 and 11 by echocardiography. At week 11, their heart morphology was studied by light and electron microscopy. Phosphorylation of Akt and Erk in heart tissues was measured by Western blot analysis. RESULTS: DOX caused myocardial damage with compromised left ventricular function, increased myocardium injury and reduced phosphorylation of Akt and Erk. DZR exerted a significant cardioprotective effect in terms of improved fractional shortening, cardiac output and cardiomyopathy score at one or more time points. We also provided the first evidence that dexarazoxane-treated animals had increased levels of Akt and Erk activation, whilst total Akt and Erk remained unchanged. CONCLUSIONS: Our results showed that the cardioprotective effect of dexarazoxane has been sustained beyond the treatment period. The data also suggested that activation of the Akt and Erk signaling pathways was regulated in the course of DOX-induced cardiomyopathy and protection by DZR.
Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Cardiomiopatias/prevenção & controle , Quelantes/uso terapêutico , Doxorrubicina/efeitos adversos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Proto-Oncogênicas c-akt/biossíntese , Razoxano/uso terapêutico , Animais , Western Blotting , Peso Corporal/efeitos dos fármacos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/enzimologia , Cardiomiopatias/patologia , Quelantes/administração & dosagem , Ecocardiografia , Masculino , Microscopia Eletrônica , Mitocôndrias Cardíacas/ultraestrutura , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Miocárdio/enzimologia , Miocárdio/ultraestrutura , Tamanho do Órgão/efeitos dos fármacos , Fosforilação , Ratos , Ratos Sprague-Dawley , Razoxano/administração & dosagem , Regulação para CimaRESUMO
OBJECTIVE: To investigate the influence of cervical sympathetic nerve block (SB) on blood flow volume and barrier function of intestinal mucosa after combined radiation and burn injury in rat. METHODS: SD rats were divided into three groups: control (n = 18), combined injury group (n = 100, rats with Co gamma ray body irradiation with a dose of 5 Gy plus 15% TBSA full-thickness burn injury), and combined injury with SB treatment (n = 100, with the same dose of gamma-ray irradiation and burn injury, treated with SB). Twenty rats were sacrificed on 0, 1, 5, 7 days after combined injuries for various observations. SB was conducted with injection of ropivhydrochloride into the neck bilaterally for the SB group, and same amount of normal saline was injected instead in the combined injury group. Blood flow volume, changes in villus height and crypt depth in jejunum, Na(+)-K+ ATPase activity, permeability of small intestine were measured at different time-points. RESULTS: The blood flow volume in small intestinal mucosal on 1 post-injury days (PID) [(0.29 +/- 0.07) ml x min(-1) x g(-1)] were obviously decreased than that in normal controls [(1.26 +/- 0.23) ml x min(-1) x g(-1), P < 0.01 ], with serious destruction of pit cells, decrease in intestinal mucosal Na(+)-K+ ATPase activity, and increase in intestinal mucosal permeability. Compared with combined injury group, the blood flow volume was [(0.82 +/- 0.11) ml x min(-1) x g(-1) 1 day after combined injury, P < 0.01], and the Na(+)-K+ ATPase activity was obviously increased, and the permeability of small intestine was ameliorated. CONCLUSION: SB can increase blood flow volume of rat small intestine after combined radiation and burn injury, promote the repair of intestinal epithelium and improve the barrier function of the intestinal wall.