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1.
Brain Struct Funct ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34626230

RESUMO

To date, ischemia-induced damage to dendritic spines has attracted considerable attention, while the possible effects of ischemia on presynaptic components has received relatively less attention. To further examine ischemia-induced changes in pre- and postsynaptic specializations in the hippocampal CA1 subfield, we modeled global cerebral ischemia with two-stage 4-vessel-occlusion in rats, and found that three postsynaptic markers, microtubule-associated protein 2 (MAP2), postsynaptic density protein 95 (PSD95), and filamentous F-actin (F-actin), were all substantially decreased in the CA1 subfield after ischemia/reperfusion (I/R). Although no significant change was detected in synapsin I, a presynaptic marker, in the CA1 subfield at the protein level, confocal microscopy revealed that the number and size of synapsin I puncta were significantly changed in the CA1 stratum radiatum after I/R. The size of synapsin I puncta became slightly, but significantly reduced on Day 1.5 after I/R. From Days 2 to 7 after I/R, the number of synapsin I puncta became moderately decreased, while the size of synapsin I puncta was significantly increased. Interestingly, some enlarged puncta of synapsin I were observed in close proximity to the dendritic shafts of CA1 pyramidal cells. Due to the more substantial decrease in the number of F-actin puncta, the ratio of synapsin I/F-actin puncta was significantly increased after I/R. The decrease in synapsin I puncta size in the early stage of I/R may be the result of excessive neurotransmitter release due to I/R-induced hyperexcitability in CA3 pyramidal cells, while the increase in synapsin I puncta in the later stage of I/R may reflect a disability of synaptic vesicle release due to the loss of postsynaptic contacts.

2.
Chem Biodivers ; 18(8): e2100049, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34118114

RESUMO

We aimed to investigate the impact of apigenin on LOX-1, Bcl-2, and Bax expression in hyperlipidemia rats and explore the possible molecular pathological mechanism of apigenin in improving hyperlipidemia and preventing atherosclerosis. In hyperlipidemia models, the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and the LOX-1 protein expression were apparently increased (P<0.01), while the high-density lipoprotein cholesterol (HDL-c) levels and the ratio of Bcl-2/Bax were reduced significantly (P<0.01) in comparison with the standard control group. After the treatment of apigenin, the levels of TC, TG, LDL-c, and the LOX-1 protein expression were noticeably decreased (P<0.01), while the levels of HDL-c and the Bcl-2/Bax ratio were increased (P<0.01). The intima was thickened and had protrusions in the hyperlipidemia model group compared to the normal control group. In comparison with the atherosclerosis model group, the degree of aortic lesions in the low-dose, middle-dose, high-dose groups was alleviated. Apigenin can reduce the level of blood lipid, improve hyperlipidemia, and prevent atherosclerosis in hyperlipidemia rats. The molecular mechanism may be related to inhibiting LOX-1 gene expression and increasing the Bcl-2/Bax ratio.


Assuntos
Apigenina/farmacologia , Expressão Gênica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores Depuradores Classe E/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Apigenina/uso terapêutico , Colesterol/sangue , Modelos Animais de Doenças , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/patologia , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Ratos Sprague-Dawley , Receptores Depuradores Classe E/genética , Triglicerídeos/sangue , Proteína X Associada a bcl-2/genética
3.
J Med Virol ; 93(7): 4247-4257, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33724490

RESUMO

To provide instructive clues for clinical practice and further research of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we analyzed the existing literature on viral neuroinvasion of SARS-CoV-2 in coronavirus disease 2019 (COVID-19) patients. To date, SARS-CoV-2 has been detected in the cerebrospinal fluid (CSF) or brain parenchyma in quite a few patients, which provide undeniable evidence for the neuroinvasive potential of this novel coronavirus. In contrast with the cerebrum and cerebellum, the detection rate of SARS-CoV-2 was higher in the olfactory system and the brainstem, both of which also showed severe microgliosis and lymphocytic infiltrations. As compared with the number of patients who underwent viral testing in the central nervous system (CNS), the number of patients showing positive results seems very small. However, it seems too early to conclude that the neuroinvasion of SARS-CoV-2 is rare in COVID-19 patients because the detection methods or sampling procedures in some studies may not be suitable or sufficient to reveal the CNS infection induced by neurotropic viruses. Moreover, the primary symptoms and/or causes of death were distinctly different among examined patients, which probably caused more conspicuous pathological changes than those due to the direct infection that usually localized to specific brain areas. Unfortunately, most autopsy studies did not provide sufficient details about neurological symptoms or suspected diagnoses of the examined patients, and the documentation of neuropathological changes was often incomplete. Given the complex pathophysiology of COVID-19 and the characteristics of neurotropic viruses, it is understandable that any study of the CNS infection may inevitably have limitations.


Assuntos
Encéfalo/patologia , COVID-19/patologia , Líquido Cefalorraquidiano/virologia , Bulbo Olfatório/virologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Encéfalo/virologia , Humanos , Doenças do Sistema Nervoso/virologia , Mucosa Olfatória/virologia , SARS-CoV-2/isolamento & purificação
4.
Aging (Albany NY) ; 13(3): 4713-4730, 2021 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-33582654

RESUMO

The peculiar features of coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), are challenging the current biological knowledge. Early in Feb, 2020, we suggested that SARS-CoV-2 may possess neuroinvasive potential similar to that of many other coronaviruses. Since then, a variety of neurological manifestations have been associated with SARS-CoV-2 infection, which was supported in some patients with neuroimaging and/or cerebrospinal fluid tests. To date, at least 27 autopsy studies on the brains of COVID-19 patients can be retrieved through PubMed/MEDLINE, among which neuropathological alterations were observed in the brainstem in 78 of 134 examined patients, and SARS-CoV-2 nucleic acid and viral proteins were detected in the brainstem in 16/49 (32.7%) and 18/71 (25.3%) cases, respectively. To shed some light on the peculiar respiratory manifestations of COVID-19 patients, this review assessed the existing evidence about the neurogenic mechanism underlying the respiratory failure induced by SARS-CoV-2 infection. Acknowledging the neurological involvement has important guiding significance for the prevention, treatment, and prognosis of SARS-CoV-2 infection.


Assuntos
COVID-19 , Doenças do Sistema Nervoso , SARS-CoV-2 , COVID-19/diagnóstico , COVID-19/fisiopatologia , Líquido Cefalorraquidiano/virologia , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/virologia , Neuroimagem/métodos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade
5.
J Med Virol ; 93(3): 1304-1313, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33002209

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a significant and urgent threat to global health. This review provided strong support for central nervous system (CNS) infection with SARS-CoV-2 and shed light on the neurological mechanism underlying the lethality of SARS-CoV-2 infection. Among the published data, only 1.28% COVID-19 patients who underwent cerebrospinal fluid (CSF) tests were positive for SARS-CoV-2 in CSF. However, this does not mean the absence of CNS infection in most COVID-19 patients because postmortem studies revealed that some patients with CNS infection showed negative results in CSF tests for SARS-CoV-2. Among 20 neuropathological studies reported so far, SARS-CoV-2 was detected in the brain of 58 cases in nine studies, and three studies have provided sufficient details on the CNS infection in COVID-19 patients. Almost all in vitro and in vivo experiments support the neuroinvasive potential of SARS-CoV-2. In infected animals, SARS-CoV-2 was found within neurons in different brain areas with a wide spectrum of neuropathology, consistent with the reported clinical symptoms in COVID-19 patients. Several lines of evidence indicate that SARS-CoV-2 used the hematopoietic route to enter the CNS. But more evidence supports the trans-neuronal hypothesis. SARS-CoV-2 has been found to invade the brain via the olfactory, gustatory, and trigeminal pathways, especially at the early stage of infection. Severe COVID-19 patients with neurological deficits are at a higher risk of mortality, and only the infected animals showing neurological symptoms became dead, suggesting that neurological involvement may be one cause of death.


Assuntos
Encéfalo/virologia , COVID-19/virologia , Viroses do Sistema Nervoso Central/virologia , Neurônios/virologia , SARS-CoV-2/patogenicidade , Animais , COVID-19/mortalidade , COVID-19/fisiopatologia , Viroses do Sistema Nervoso Central/mortalidade , Viroses do Sistema Nervoso Central/fisiopatologia , Líquido Cefalorraquidiano/virologia , Humanos , Vias Neurais , SARS-CoV-2/isolamento & purificação
6.
J Med Virol ; 92(11): 2269-2271, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32525575

RESUMO

As compared to many other viral pulmonary infections, there existed several peculiar manifestations in the COVID-19 patients, including the "silence" of pneumonia in both mild and severe cases and a long intensive care unit stay for those requiring invasive mechanical ventilation. Similar silent pneumonia has been documented in the infectioninduced by H5N1 influenza virus HK483 and was found to result from the direct attack of the virus on the bronchopulmonary C-fibers at the early stage and the final infection in the brainstem at the late stage. The long stay of critical patients in the intensive care unit is possibly due to the depression of central respiratory drive, which resulted in the failure to wean from the mechanic ventilation. Carotid and aortic bodies and bronchopulmonary C-fibers are two key peripheral components responsible for the chemosensitive responses in the respiratory system, while triggering respiratory reflexes depends predominantly on the putative chemosensitive neurons located in the pontomedullary nuclei. In view of the findings for the H5N1 influenza virus, the silence of pneumonia induced by SARS-CoV-2 may be due to the possible impairment of peripheral chemosensitive reflexes as well as the damage to the respiratory-related central neurons.


Assuntos
COVID-19/complicações , COVID-19/fisiopatologia , Rede Nervosa/patologia , Dispneia , Humanos , Virus da Influenza A Subtipo H5N1 , Influenza Humana , Unidades de Terapia Intensiva , Rede Nervosa/virologia , SARS-CoV-2/patogenicidade , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X
7.
J Med Virol ; 92(7): 707-709, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32246783

RESUMO

In a recent review, we have suggested a neuroinvasive potential of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its possible role in the causation of acute respiratory failure of coronavirus disease 2019 (COVID-19) patients (J Med Viol doi: 10.1002/jmv.25728), based upon the clinical and experimental data available on the past SARS-CoV-1 and the recent SARS-CoV-2 pandemic. In this article, we provide new evidence recently reported regarding the neurotropic potential of SARS-CoV-2 and respond to several comments on our previously published article. In addition, we also discuss the peculiar manifestations of respiratory failure in COVID-19 patients and the possible involvement of nervous system.


Assuntos
Coronavirus , Insuficiência Respiratória , Vírus da SARS , Betacoronavirus , COVID-19 , Infecções por Coronavirus , Humanos , Pandemias , Pneumonia Viral , SARS-CoV-2
8.
J Med Virol ; 92(6): 552-555, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32104915

RESUMO

Following the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), another highly pathogenic coronavirus named SARS-CoV-2 (previously known as 2019-nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS-CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical symptoms similar to those reported for SARS-CoV and MERS-CoV. The most characteristic symptom of patients with COVID-19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID-19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS-CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse-connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS-CoV and SARS-CoV2, it remains to make clear whether the potential invasion of SARS-CoV2 is partially responsible for the acute respiratory failure of patients with COVID-19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS-CoV-2-induced respiratory failure.


Assuntos
Betacoronavirus/patogenicidade , Sistema Nervoso Central/virologia , Infecções por Coronavirus/epidemiologia , Cefaleia/virologia , Pandemias , Pneumonia Viral/epidemiologia , Vírus da SARS/patogenicidade , Betacoronavirus/fisiologia , COVID-19 , Sistema Nervoso Central/fisiopatologia , China/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Cefaleia/diagnóstico , Cefaleia/fisiopatologia , Humanos , Pulmão/fisiopatologia , Pulmão/virologia , Mecanotransdução Celular , Náusea/diagnóstico , Náusea/fisiopatologia , Náusea/virologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/virologia , Vírus da SARS/fisiologia , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/fisiopatologia , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia , Vômito/diagnóstico , Vômito/fisiopatologia , Vômito/virologia
9.
J Chem Neuroanat ; 101: 101682, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31494221

RESUMO

The down-regulation of microtubule proteins has been widely documented in the ischemic brain, but the temporal or spatial alteration of microtubules has not been systematically investigated in the vulnerable areas after ischemia. By examining the stability and distribution of microtubules following transient global ischemia, we found that the biomarkers of stable microtubules, MAP2 and acetylated α-tubulin, became significantly down-regulated in the CA1 stratum radiatum of rat hippocampus and that the neuron-specific microtubule protein, class III ß-tubulin, was progressively decreased in the same region. Surprisingly, pan-ß-tubulin, which is expressed at a low level in glial cells under physiological conditions, was significantly increased in reactive astrocytes after ischemia. The finding was supported by protein quantification and confocal microscopy analysis, and consistent with the different vulnerabilities of neuronal and glial cells to the ischemic insult. To our knowledge, the different responses of microtubules between neuronal and glial cells have not been described in the ischemic brain before. The deconstruction of microtubules in the neurons is expected to contribute to the selective and delayed neuronal death in the vulnerable brain regions, while the increased microtubules in the reactive astrocytes may play an important role in the shape conversion of astrocytes induced by ischemia.


Assuntos
Isquemia Encefálica/patologia , Região CA1 Hipocampal/patologia , Microtúbulos/patologia , Animais , Masculino , Neuroglia/patologia , Neurônios/patologia , Ratos , Ratos Wistar
10.
Brain Res ; 1720: 146297, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31233713

RESUMO

Transient global ischemia usually results in delayed neuronal death in selective brain regions, prior to which a rapid loss of dendritic spines has been widely reported in these regions. Dendritic spines are characterized by a highly branched meshwork of actin cytoskeleton (F-actin), which is extremely vulnerable to the ATP-depleted conditions such as hypoxia/ischemia. However, the ischemia-induced changes of F-actin are still not clarified in the vulnerable brain areas. This study was designed to examine the temporal and spatial alterations of F-actin in the CA1 subfield of rat hippocampus following reperfusion after global cerebral ischemia. Phalloidin staining and confocal microscopic examination showed that F-actin disappeared from the dentritic spines in the CA1 stratum radiatum, but aggregated into thread- or fiber-like structures on days 1.5-2 after ischemia. This was followed by a nearly complete loss of F-actin in the CA1 subfield on days 3-7 after ischemia. Colocalization analysis demonstrated that the F-actin threads or fibers were located mainly within the dentritic trunks. As revealed by Nissl and Fluoro-Jade B staining, the decrease of F-actin proceeded concurrently with the evolution of ischemic damage. Consistently, western blots detected a significant decrease of F-/G-actin ratio in the dissected CA1 subfield after ischemia. To our knowledge, this is the first report on the change of F-actin in the ischemic brain. Although the underlying mechanisms remain to be elucidated, our findings may provide an important structural clue for the neuronal dysfunction induced by ischemia.


Assuntos
Citoesqueleto de Actina/metabolismo , Isquemia Encefálica/fisiopatologia , Região CA1 Hipocampal/metabolismo , Citoesqueleto de Actina/fisiologia , Actinas/metabolismo , Animais , Isquemia Encefálica/metabolismo , Região CA1 Hipocampal/fisiopatologia , Dendritos/metabolismo , Espinhas Dendríticas/metabolismo , Fluoresceínas , Hipocampo/metabolismo , Isquemia , Ataque Isquêmico Transitório , Masculino , Neurônios/metabolismo , Ratos , Ratos Wistar , Lobo Temporal/metabolismo
11.
Epilepsy Res ; 154: 26-33, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31022637

RESUMO

Rogressive deconstruction of filament actin (F-actin) in hippocampal neurons in the epileptic brain have been associated with epileptogenesis. Previous clinical studies suggest that glucocorticoids treatment plays beneficial roles in refractory epilepsy. Glucocorticoids treatment affects dendritic spine morphology by regulating local glucocorticoid receptors and F-actin cytoskeleton dynamics. However, how glucocorticoids regulate epileptogenesis by controlling F-actin cytoskeleton is not clear yet. Here we study the function of glucocorticoids in epileptogenesis by examining F-actin abundance, hippocampal neuron number, and synaptic markers in pilocarpine-induced epileptic mice in the presence or absence of dexamethasone (DEX) treatment. We found that spontaneous seizure duration was significantly reduced; F-actin damage in hippocampal subfields was remarkably attenuated; loss of pyramidal cells was dramatically decreased; more intact synaptic structures indicated by pre- and postsynaptic markers were preserved in multiple hippocampal regions after DEX treatment. However, the number of ZNT3 positive particles in the molecular layer in the hippocampus of pilocarpine epileptic mice was not altered after DEX treatment. Although not sufficient to cease epileptogenesis, our results suggest that dexamethasone treatment ameliorates the damage of epileptic brain by stabilizing F-actin cytoskeleton in the pilocarpine epileptic mice.


Assuntos
Citoesqueleto de Actina/metabolismo , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Epilepsia/metabolismo , Hipocampo/metabolismo , Pilocarpina/toxicidade , Citoesqueleto de Actina/química , Animais , Anti-Inflamatórios/farmacologia , Dexametasona/farmacologia , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Hipocampo/química , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR
12.
J Chem Neuroanat ; 98: 17-26, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30872184

RESUMO

Disruption of microtubule cytoskeleton plays an important role during the evolution of brain damage after transient cerebral ischemia. However, it is still unclear whether microtubule-stabilizing drugs such as epothilone D (EpoD) have a neuroprotective action against the ischemia-induced brain injury. This study examined the effects of pre- and postischemic treatment with different doses of EpoD on the microtubule damage and the delayed neuronal death in the hippocampal CA1 subfield on day 2 following reperfusion after 13-min global cerebral ischemia. Our results showed that systemic treatment with 0.5 mg/kg EpoD only slightly alleviated the microtubule disruption and the CA1 neuronal death, while treatment with 3.0 mg/kg EpoD was not only ineffective against the CA1 neuronal death, but also produced additional damage in the dentate gyrus in some ischemic rats. Since the pyramidal cells in the CA1 subfield and the granule neurons in the dentate gyrus are known to be equipped with dynamically different microtubule systems, this finding indicates that the effects of microtubule-disrupting drugs may be unpredictably complicated in the central nervous system.


Assuntos
Região CA1 Hipocampal/efeitos dos fármacos , Epotilonas/farmacologia , Ataque Isquêmico Transitório/patologia , Células Piramidais/efeitos dos fármacos , Moduladores de Tubulina/farmacologia , Animais , Região CA1 Hipocampal/patologia , Morte Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Piramidais/patologia , Ratos , Ratos Wistar
13.
Epilepsy Res ; 140: 138-147, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29358156

RESUMO

After status epilepticus (SE), actin cytoskeleton (F-actin) becomes progressively deconstructed in the hippocampus, which is consistent with the delayed pyramidal cell death in both time course and spatial distribution. A variety of experiments show that calcineurin inhibitors such as FK506 are able to inhibit the SE-induced actin depolymerization. However, it is still unclear what changes happen to the F-actin in the epileptic brain after FK506 treatment. A pilocarpine model of SE in mice was used to examine the effects of FK506 on the F-actin in the hippocampal neurons. The post SE (PSE) mice with or without FK506 treatment were monitored consecutively for 14 days to examine the frequency and duration of spontaneous seizures. The effects of FK506 on the activity of cofilin and actin dynamics were assessed at 7 and 14 d PSE by western blots. The organization of F-actin, neuronal cell death, and glial reactions were investigated by phalloidin staining, histological and immunocytochemical staining, respectively. As compared to the PSE + vehicle mice, FK506 treatment significantly decreased the frequency and duration of spontaneous seizures. Relative to the PSE + vehicle mice, western blots detected a partial restoration of phosphorylated cofilin and a significant increase of F/G ratio in the hippocampus after FK506 treatment. In the PSE + vehicle mice, almost no F-actin puncta were left in the CA1 and CA3 subfields at 7 and 14 d PSE. FK506-treated PSE mice showed a similar decrease of F-actin, but the extent of damage was significantly ameliorated. Consistently, the surviving neurons became significantly increased in number after FK506 treatment, relative to the PSE + vehicle groups. After FK506 treatment, microglial reaction was partially inhibited, but the expression of GFAP was not significantly changed, compared to the PSE + vehicle mice. The results suggest that post-epileptic treatment with FK506 ameliorated, but could not stop the deconstruction of F-actin or the delayed neuronal loss in the PSE mice.


Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Inibidores de Calcineurina/farmacologia , Neuroglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Estado Epiléptico/tratamento farmacológico , Tacrolimo/farmacologia , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Animais , Anticonvulsivantes/farmacologia , Proteínas de Ligação ao Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Camundongos Endogâmicos ICR , Proteínas dos Microfilamentos/metabolismo , Neuroglia/metabolismo , Neuroglia/patologia , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Pilocarpina , Distribuição Aleatória , Estado Epiléptico/metabolismo , Estado Epiléptico/patologia
14.
Tissue Cell ; 49(2 Pt B): 336-344, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28187870

RESUMO

In the central canal, F-actin is predominantly localized in the apical region, forming a ring-like structure around the circumference of the lumen. However, an exception is found in the medulla oblongata, where the apical F-actin becomes interrupted in the ventral aspect of the canal. To clarify the precise localization of F-actin, the fluorescence signals for F-actin were converted to the peroxidase/DAB reaction products in this study by a phalloidin-based ultrastructural technique, which demonstrated that F-actin is located mainly in the microvilli and terminal webs in the ependymocytes. It is because the ventrally oriented ependymocytes do not possess well-developed microvilli or terminal web that led to a discontinuous labeling of F-actin in the medullary canal. Since spinal motions can change the shape and size of the central canal, we next examined the cytoskeletons in the medullary canal in both rats and monkeys, because these two kinds of animals show different kinematics at the atlanto-occipital articulation. Our results first demonstrated that the apical F-actin in the medullary canal is differently organized in the animals with different head-neck kinemics, which suggests that the mechanic stretching of spinal motions is capable of inducing F-actin reorganization and the subsequent cell-shape changes in the central canal.


Assuntos
Citoesqueleto de Actina/ultraestrutura , Actinas/metabolismo , Bulbo/ultraestrutura , Canal Medular/ultraestrutura , Citoesqueleto de Actina/metabolismo , Actinas/isolamento & purificação , Animais , Fenômenos Biomecânicos , Haplorrinos , Bulbo/metabolismo , Ratos , Canal Medular/metabolismo
15.
Zhongguo Gu Shang ; 30(3): 198-201, 2017 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-29349954

RESUMO

OBJECTIVE: To retrospectively explore the effects of damage control orthopaedics concept on coagulation and curative effects in unstable pelvic fractures and multiple fractures of limbs. METHODS: From March 2014 to December 2015, 40 patients with unstable pelvic fractures and limbs multiple fractures in treatment group included 22 males and 18 females with an average age of (39.00±4.12) years old were treated with the damage control orthopaedics concept, the ISS score was (25.36±10.81) on average;Other 40 patients with the same trauma in conventional group included 25 males and 15 females with an average age of (38.00±3.24) years old were treated with conventional method from January 2012 to January 2014 served as control, the average ISS score was 26.56±11.44. Matta criteria and Majeed function standard were used respectively to evaluate the fracture reduction and therapeutic effects postoperatively. Coagulation function on the 7th day postoperatively was compared between two groups. RESULTS: All patients were followed up for 6 to 24 months. According to Matta criteria, the fracture reduction of the treatment group and the conventional group were (7.38±5.09) mm and (10.11±6.53) mm, respectively (P<0.05). Majeed functional results of the treatment group and the conventional group were (86.12±6.84) points and (77.53±8.30) points, respectively (P<0.05). On the 7th day after surgery, PT, APTT, TT of the treatment group were significantly higher than that of the control group;and Fib of the treatment group was also significantly lower than that of the conventional group(P<0.05). CONCLUSIONS: The concept of damage control orthopaedics could effectively improve coagulation function of the patients with unstable pelvic fractures and limbs multiple fractures, thus are beneficial to the functional recovery as well as improve the curative effect postoperatively.


Assuntos
Traumatismos do Braço/cirurgia , Fraturas Ósseas/cirurgia , Fraturas Múltiplas/cirurgia , Ossos da Perna/lesões , Ortopedia/métodos , Ossos Pélvicos/lesões , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
16.
Hypertension ; 68(3): 654-66, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27432858

RESUMO

The role of type III transforming growth factor-ß receptor (TßRIII) in the pathogenesis of heart diseases remains largely unclear. Here, we investigated the functional role and molecular mechanisms of TßRIII in the development of myocardial hypertrophy. Western blot and quantitative real time-polymerase chain reaction analyses revealed that the expression of TßRIII was significantly elevated in human cardiac hypertrophic samples. Consistently, TßRIII expression was substantially increased in transverse aortic constriction (TAC)- and isoproterenol-induced mouse cardiac hypertrophy in vivo and in isoproterenol-induced cardiomyocyte hypertrophy in vitro. Overexpression of TßRIII resulted in cardiomyocyte hypertrophy, whereas isoproterenol-induced cardiomyocyte hypertrophy was greatly attenuated by knockdown of TßRIII in vitro. Cardiac-specific transgenic expression of TßRIII independently led to cardiac hypertrophy in mice, which was further aggravated by isoproterenol and TAC treatment. Cardiac contractile function of the mice was not altered in TßRIII transgenic mice; however, TAC led to significantly decreased cardiac contractile function in TßRIII transgenic mice compared with control mice. Conversely, isoproterenol- and TAC-induced cardiac hypertrophy and TAC-induced cardiac contractile function impairment were partially reversed by suppression of TßRIII in vivo. Our data suggest that TßRIII mediates stress-induced cardiac hypertrophy through activation of Ca(2+)/calmodulin-dependent protein kinase II, which requires a physical interaction of ß-arrestin2 with both TßRIII and calmodulin-dependent protein kinase II. Our findings indicate that stress-induced increase in TßRIII expression results in cardiac hypertrophy through ß-arrestin2-dependent activation of calmodulin-dependent protein kinase II and that transforming growth factor-ß and ß-adrenergic receptor signaling are not involved in spontaneous cardiac hypertrophy in cardiac-specific transgenic expression of TßRIII mice. Our findings may provide a novel target for control of myocardial hypertrophy.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiomegalia/genética , Fator de Crescimento Transformador beta/metabolismo , beta-Arrestina 2/metabolismo , Análise de Variância , Animais , Biópsia por Agulha , Cardiomegalia/patologia , Células Cultivadas , Modelos Animais de Doenças , Humanos , Imuno-Histoquímica , Isoproterenol/farmacologia , Camundongos , Camundongos Transgênicos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Distribuição Aleatória , Sensibilidade e Especificidade , Proteínas com Domínio T/genética
17.
Sci Rep ; 6: 26365, 2016 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-27193057

RESUMO

We study the connections between local quantum coherence (LQC) based on Wigner-Yanase skew information and quantum phase transitions (QPTs). When applied on the one-dimensional Hubbard, XY spin chain with three-spin interaction, and Su-Schrieffer-Heeger models, the LQC and its derivatives are used successfully to detect different types of QPTs in these spin and fermionic systems. Furthermore, the LQC is effective as the quantum discord (QD) in detecting QPTs at finite temperatures, where the entanglement has lost its effectiveness. We also demonstrate that the LQC can exhibit different behaviors in many forms compared with the QD.

18.
J Cell Physiol ; 230(2): 337-46, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24962810

RESUMO

Anoctamin1 (ANO1) encodes a Ca(2+)-activated chloride (Cl(-)) channel (CaCC) in variety tissues of many species. Whether ANO1 expresses and functions as a CaCC in cardiomyocytes remain unknown. The objective of this study is to characterize the molecular and functional expression of ANO1 in cardiac myocytes and the role of ANO1-encoded CaCCs in ischemia-induced arrhythmias in the heart. Quantitative real-time RT-PCR, immunofluorescence staining assays, and immunohistochemistry identified the molecular expression, location, and distribution of ANO1 in mouse ventricular myocytes (mVMs). Patch-clamp recordings combined with pharmacological analyses found that ANO1 was responsible for a Ca(2+)-activated Cl(-) current (I(Cl.Ca)) in cardiomyocytes. Myocardial ischemia led to a significant increase in the current density of I(Cl.Ca), which was inhibited by a specific ANO1 inhibitor, T16A(inh)-A01, and an antibody targeting at the pore area of ANO1. Moreover, cardiomyocytes isolated from mice with ischemia-induced arrhythmias had an accelerated early phase 1 repolarization of action potentials (APs) and a deeper "spike and dome" compared to control cardiomyocytes from non-ischemia mice. Application of the antibody targeting at ANO1 pore prevented the ischemia-induced early phase 1 repolarization acceleration and caused a much shallower "spike and dome". We conclude that ANO1 encodes CaCC and plays a significant role in the phase 1 repolarization of APs in mVMs. The ischemia-induced increase in ANO1 expression may be responsible for the increased density of I(Cl.Ca) in the ischemic heart and may contribute, at least in part, to ischemia-induced arrhythmias.


Assuntos
Arritmias Cardíacas/metabolismo , Cálcio/metabolismo , Canais de Cloreto/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Potenciais de Ação/fisiologia , Animais , Anoctamina-1 , Agonistas dos Canais de Cloreto/farmacologia , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos BALB C , Miócitos Cardíacos/efeitos dos fármacos , Técnicas de Patch-Clamp , Traumatismo por Reperfusão/metabolismo
19.
Br J Pharmacol ; 171(15): 3680-92, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24758567

RESUMO

BACKGROUND AND PURPOSE: The molecular identity of calcium-activated chloride channels (CaCCs) in vascular endothelial cells remains unknown. This study sought to identify whether anoctamin-1 (Ano1, also known as TMEM16A) functions as a CaCC and whether hypoxia alters the biophysical properties of Ano1 in mouse cardiac vascular endothelial cells (CVECs). EXPERIMENTAL APPROACH: Western blot, quantitative real-time PCR, confocal imaging analysis and patch-clamp analysis combined with pharmacological approaches were used to determine whether Ano1 was expressed and functioned as CaCC in CVECs. KEY RESULTS: Ano1 was expressed in CVECs. The biophysical properties of the current generated in the CVECs, including the Ca(2+) and voltage dependence, outward rectification, anion selectivity and the pharmacological profile, are similar to those described for CaCCs. The density of ICl ( C a) detected in CVECs was significantly inhibited by T16Ainh -A01, an Ano1 inhibitor, and a pore-targeting, specific anti-Ano1 antibody, and was markedly decreased in Ano1 gene knockdown CVECs. The density of ICl ( C a) was significantly potentiated in CVECs exposed to hypoxia, and this hypoxia-induced increase in the density of ICl ( C a) was inhibited by T16Ainh -A01 or anti-Ano1 antibody. Hypoxia also increased the current density of ICl ( C a) in Ano1 gene knockdown CVECs. CONCLUSIONS AND IMPLICATIONS: Ano1 formed CaCC in CVECs of neonatal mice. Hypoxia enhances Ano1-mediated ICl ( C a) density via increasing its expression, altering the ratio of its splicing variants, sensitivity to membrane voltage and to Ca(2+) . Ano1 may play a role in the pathophysiological processes during ischaemia in heart, and therefore, Ano1 might be a potential therapeutic target to prevent ischaemic damage.


Assuntos
Canais de Cloreto/fisiologia , Células Endoteliais/fisiologia , Hipóxia/fisiopatologia , Animais , Animais Recém-Nascidos , Anoctamina-1 , Sequência de Bases , Cálcio/farmacologia , Proliferação de Células , Células Cultivadas , Canais de Cloreto/genética , Células Endoteliais/efeitos dos fármacos , Inativação Gênica , Proteínas de Fluorescência Verde/genética , Ventrículos do Coração/citologia , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Transfecção
20.
Rev Sci Instrum ; 85(3): 034701, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24689606

RESUMO

Synchronization sampling is very important in underwater towed array system where every acquisition node (AN) samples analog signals by its own analog-digital converter (ADC). In this paper, a simple and effective synchronization sampling method is proposed to ensure synchronized operation among different ANs of the underwater towed array system. We first present a master-slave synchronization sampling model, and then design a high accuracy phase-locked loop to synchronize all delta-sigma ADCs to a reference clock. However, when the master-slave synchronization sampling model is used, both the time-delay (TD) of messages traveling along the wired transmission medium and the jitter of the clocks will bring out synchronization sampling error (SSE). Therefore, a simple method is proposed to estimate and compensate the TD of the messages transmission, and then another effective method is presented to overcome the SSE caused by the jitter of the clocks. An experimental system with three ANs is set up, and the related experimental results verify the validity of the synchronization sampling method proposed in this paper.

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