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Pesquisa : D02.065.884.150 [Categoria DeCS]
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  1 / 1827 MEDLINE  
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[PMID]:28692063
[Au] Autor:Karimy JK; Zhang J; Kurland DB; Theriault BC; Duran D; Stokum JA; Furey CG; Zhou X; Mansuri MS; Montejo J; Vera A; DiLuna ML; Delpire E; Alper SL; Gunel M; Gerzanich V; Medzhitov R; Simard JM; Kahle KT
[Ad] Endereço:Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, USA.
[Ti] Título:Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus.
[So] Source:Nat Med;23(8):997-1003, 2017 Aug.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The choroid plexus epithelium (CPE) secretes higher volumes of fluid (cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions as the blood-CSF barrier to gate immune cell entry into the central nervous system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH), is a common disease usually treated by suboptimal CSF shunting techniques. PHH is classically attributed to primary impairments in CSF reabsorption, but little experimental evidence supports this concept. In contrast, the potential contribution of CSF secretion to PHH has received little attention. In a rat model of PHH, we demonstrate that IVH causes a Toll-like receptor 4 (TLR4)- and NF-κB-dependent inflammatory response in the CPE that is associated with a ∼3-fold increase in bumetanide-sensitive CSF secretion. IVH-induced hypersecretion of CSF is mediated by TLR4-dependent activation of the Ste20-type stress kinase SPAK, which binds, phosphorylates, and stimulates the NKCC1 co-transporter at the CPE apical membrane. Genetic depletion of TLR4 or SPAK normalizes hyperactive CSF secretion rates and reduces PHH symptoms, as does treatment with drugs that antagonize TLR4-NF-κB signaling or the SPAK-NKCC1 co-transporter complex. These data uncover a previously unrecognized contribution of CSF hypersecretion to the pathogenesis of PHH, demonstrate a new role for TLRs in regulation of the internal brain milieu, and identify a kinase-regulated mechanism of CSF secretion that could be targeted by repurposed US Food and Drug Administration (FDA)-approved drugs to treat hydrocephalus.
[Mh] Termos MeSH primário: Hemorragia Cerebral/imunologia
Líquido Cefalorraquidiano/secreção
Plexo Corióideo/secreção
Hidrocefalia/imunologia
NF-kappa B/imunologia
Receptor 4 Toll-Like/imunologia
[Mh] Termos MeSH secundário: Acetazolamida/farmacologia
Animais
Antioxidantes/farmacologia
Western Blotting
Bumetanida/farmacologia
Hemorragia Cerebral/complicações
Ventrículos Cerebrais
Plexo Corióideo/efeitos dos fármacos
Plexo Corióideo/imunologia
Diuréticos/farmacologia
Técnicas de Silenciamento de Genes
Técnicas de Inativação de Genes
Hidrocefalia/etiologia
Hidrocefalia/metabolismo
Immunoblotting
Imuno-Histoquímica
Imunoprecipitação
Inflamação
Prolina/análogos & derivados
Prolina/farmacologia
Proteínas Serina-Treonina Quinases/metabolismo
Ratos
Ratos Wistar
Salicilanilidas/farmacologia
Membro 2 da Família 12 de Carreador de Soluto/metabolismo
Sulfonamidas/farmacologia
Tiocarbamatos/farmacologia
Receptor 4 Toll-Like/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Diuretics); 0 (NF-kappa B); 0 (Salicylanilides); 0 (Slc12a2 protein, mouse); 0 (Solute Carrier Family 12, Member 2); 0 (Sulfonamides); 0 (Thiocarbamates); 0 (Tlr4 protein, rat); 0 (Toll-Like Receptor 4); 0 (ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate); 0Y2S3XUQ5H (Bumetanide); 135467-92-4 (prolinedithiocarbamate); 9DLQ4CIU6V (Proline); EC 2.7.1.- (Stk39 protein, mouse); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EUL532EI54 (closantel); O3FX965V0I (Acetazolamide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170711
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4361


  2 / 1827 MEDLINE  
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[PMID]:28192112
[Au] Autor:Römermann K; Fedrowitz M; Hampel P; Kaczmarek E; Töllner K; Erker T; Sweet DH; Löscher W
[Ad] Endereço:Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Germany.
[Ti] Título:Multiple blood-brain barrier transport mechanisms limit bumetanide accumulation, and therapeutic potential, in the mammalian brain.
[So] Source:Neuropharmacology;117:182-194, 2017 May 01.
[Is] ISSN:1873-7064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:There is accumulating evidence that bumetanide, which has been used over decades as a potent loop diuretic, also exerts effects on brain disorders, including autism, neonatal seizures, and epilepsy, which are not related to its effects on the kidney but rather mediated by inhibition of the neuronal Na-K-Cl cotransporter isoform NKCC1. However, following systemic administration, brain levels of bumetanide are typically below those needed to inhibit NKCC1, which critically limits its clinical use for treating brain disorders. Recently, active efflux transport at the blood-brain barrier (BBB) has been suggested as a process involved in the low brain:plasma ratio of bumetanide, but it is presently not clear which transporters are involved. Understanding the processes explaining the poor brain penetration of bumetanide is needed for developing strategies to improve the brain delivery of this drug. In the present study, we administered probenecid and more selective inhibitors of active transport carriers at the BBB directly into the brain of mice to minimize the contribution of peripheral effects on the brain penetration of bumetanide. Furthermore, in vitro experiments with mouse organic anion transporter 3 (Oat3)-overexpressing Chinese hamster ovary cells were performed to study the interaction of bumetanide, bumetanide derivatives, and several known inhibitors of Oats on Oat3-mediated transport. The in vivo experiments demonstrated that the uptake and efflux of bumetanide at the BBB is much more complex than previously thought. It seems that both restricted passive diffusion and active efflux transport, mediated by Oat3 but also organic anion-transporting polypeptide (Oatp) Oatp1a4 and multidrug resistance protein 4 explain the extremely low brain concentrations that are achieved after systemic administration of bumetanide, limiting the use of this drug for targeting abnormal expression of neuronal NKCC1 in brain diseases.
[Mh] Termos MeSH primário: Barreira Hematoencefálica/fisiologia
Encéfalo/metabolismo
Bumetanida/farmacocinética
Proteínas Associadas à Resistência a Múltiplos Medicamentos/fisiologia
Transportadores de Ânions Orgânicos Sódio-Independentes/fisiologia
Proteínas de Transporte de Cátions Orgânicos/fisiologia
[Mh] Termos MeSH secundário: Animais
Transporte Biológico/efeitos dos fármacos
Barreira Hematoencefálica/efeitos dos fármacos
Encéfalo/efeitos dos fármacos
Bumetanida/análogos & derivados
Células CHO
Células Cultivadas
Cricetinae
Cricetulus
Difusão
Feminino
Moduladores de Transporte de Membrana/farmacologia
Camundongos
Transportadores de Ânions Orgânicos/antagonistas & inibidores
Transportadores de Ânions Orgânicos/genética
Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores
Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo
Probenecid/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Abcc4 protein, mouse); 0 (Membrane Transport Modulators); 0 (Multidrug Resistance-Associated Proteins); 0 (Oatp2 protein, mouse); 0 (Organic Anion Transporters); 0 (Organic Anion Transporters, Sodium-Independent); 0 (Organic Cation Transport Proteins); 0 (organic anion transport protein 3); 0Y2S3XUQ5H (Bumetanide); PO572Z7917 (Probenecid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170214
[St] Status:MEDLINE


  3 / 1827 MEDLINE  
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[PMID]:28159275
[Au] Autor:Jin R; Li L; Guo L; Li W; Shen Q
[Ad] Endereço:Institute of Seafood, Zhejiang Gongshang University, Hangzhou, China.
[Ti] Título:A graphene tip coupled with liquid chromatography tandem mass spectrometry for the determination of four synthetic adulterants in slimming supplements.
[So] Source:Food Chem;224:329-334, 2017 Jun 01.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Slimming supplements were popularly sold online driven by the increasement of obesity and the development of social networking platform. However, events of drug abuse in slimming supplements were also frequently reported. In this study, a graphene tip solid-phase extraction (Gtip SPE) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established for determining fenfluramine, phenolphthalein, bumetanide, and sibutramine in slimming supplements. It was validated in terms of linearity (0.9985-0.9995), LOD (1.8ngmL ), LOQ (5.6ngmL ), intra-day precision (<5.1%), inter-day precision (<7.3%), and recovery (82.9-95.2%). Sibutramine is the most commonly used drug, which was detected in Bihais, Galong, and Aolist, with content 12.4, 3.6, 20.3mgg , respectively. Phenolphthalein was also found with content lower than 5.2mgg . The successful application of Gtip SPE and UPLC-MS/MS method indicated its advantage in analyzing low level of contaminates resulted from violation of regulation.
[Mh] Termos MeSH primário: Depressores do Apetite/análise
Cromatografia Líquida
Suplementos Nutricionais/análise
Grafite/química
Espectrometria de Massas em Tandem
[Mh] Termos MeSH secundário: Bumetanida/análise
Ciclobutanos/análise
Fenfluramina/análise
Limite de Detecção
Fenolftaleína/análise
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Extração em Fase Sólida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Appetite Depressants); 0 (Cyclobutanes); 0Y2S3XUQ5H (Bumetanide); 2DS058H2CF (Fenfluramine); 6QK969R2IF (Phenolphthalein); 7782-42-5 (Graphite); WV5EC51866 (sibutramine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170205
[St] Status:MEDLINE


  4 / 1827 MEDLINE  
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[PMID]:28152000
[Au] Autor:Tang L; Fang X; Winesett SP; Cheng CY; Binder HJ; Rivkees SA; Cheng SX
[Ad] Endereço:Department of Pediatrics, University of Florida, Gainesville, FL, United States of America.
[Ti] Título:Bumetanide increases Cl--dependent short-circuit current in late distal colon: Evidence for the presence of active electrogenic Cl- absorption.
[So] Source:PLoS One;12(2):e0171045, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mammalian colonic epithelia consist of cells that are capable of both absorbing and secreting Cl-. The present studies employing Ussing chamber technique identified two opposing short-circuit current (Isc) responses to basolateral bumetanide in rat distal colon. Apart from the transepithelial Cl--secretory Isc in early distal colon that was inhibited by bumetanide, bumetanide also stimulated Isc in late distal colon that had not previously been identified. Since bumetanide inhibits basolateral Na+-K+-2Cl- cotransporter (NKCC) in crypt cells and basolateral K+-Cl- cotransporter (KCC) in surface epithelium, we proposed this stimulatory Isc could represent a KCC-mediated Cl- absorptive current. In support of this hypothesis, ion substitution experiments established Cl- dependency of this absorptive Isc and transport inhibitor studies demonstrated the involvement of an apical Cl- conductance. Current distribution and RNA sequencing analyses revealed that this Cl- absorptive Isc is closely associated with epithelial Na+ channel (ENaC) but is not dependent on ENaC activity. Thus, inhibition of ENaC by 10 µM amiloride or benzamil neither altered the direction nor its activity. Physiological studies suggested that this Cl- absorptive Isc senses dietary Cl- content; thus when dietary Cl- was low, Cl- absorptive Isc was up-regulated. In contrast, when dietary Cl- was increased, Cl- absorptive Isc was down-regulated. We conclude that an active Cl- extrusion mechanism exists in ENaC-expressing late distal colon and likely operates in parallel with ENaC to facilitate NaCl absorption.
[Mh] Termos MeSH primário: Bumetanida/farmacologia
Cloretos/metabolismo
Colo/efeitos dos fármacos
Colo/metabolismo
[Mh] Termos MeSH secundário: Amilorida/análogos & derivados
Amilorida/farmacologia
Animais
Bário/farmacologia
Cloretos/farmacologia
Bloqueadores do Canal de Sódio Epitelial/farmacologia
Canais Epiteliais de Sódio/genética
Canais Epiteliais de Sódio/metabolismo
Epitélio/efeitos dos fármacos
Epitélio/metabolismo
Regulação da Expressão Gênica/efeitos dos fármacos
Glibureto/farmacologia
Masculino
Técnicas de Cultura de Órgãos
Ratos Sprague-Dawley
Sódio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chlorides); 0 (Epithelial Sodium Channel Blockers); 0 (Epithelial Sodium Channels); 04659UUJ94 (benzamil); 0Y2S3XUQ5H (Bumetanide); 24GP945V5T (Barium); 7DZO8EB0Z3 (Amiloride); 9NEZ333N27 (Sodium); SX6K58TVWC (Glyburide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170203
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0171045


  5 / 1827 MEDLINE  
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[PMID]:28110691
[Au] Autor:Bou Khalil R
[Ad] Endereço:Hotel Dieu de France, Beirut, Lebanon; Saint Joseph University, Beirut, Lebanon. Electronic address: ramiboukhalil@hotmail.com.
[Ti] Título:Is insulin growth factor-1 the future for treating autism spectrum disorder and/or schizophrenia?
[So] Source:Med Hypotheses;99:23-25, 2017 Feb.
[Is] ISSN:1532-2777
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To date, no curative psychopharmacologic treatment exists for the core symptoms of autism spectrum disorder (ASD) as well as for schizophrenia. Bumatenide is a specific antagonist of the first isoform of the Na-K-Cl cotransporter (NKCC1). It is usually used as a diuretic but may also promote a decrease in intraneuronal chloride ion concentration leading to hyperpolarization in neuronal membrane and subsequent decrease in neuronal hyperexcitability. This physiologic effect has been considered to be behind the relative efficacy of bumetanide in improving symptoms of ASD and, to a lesser extent, schizophrenia. However, insulin growth factor-1 (IGF-1) shows the same physiologic effect. In addition, it may improve brain network dysconnectivity which is known to be an important neurobiological feature in ASD and schizophrenia. IGF-1 has started to prove its efficacy in improving symptoms of children with Rett syndrome, a genetic disorder that shares several clinical similarities with ASD. IGF-1 may also improve oxytocin secretion through the enhancement of the transient potential receptor V2 channel function. Accordingly, IGF-1 should be studied as a potential treatment of ASD and other mental disorders characterized with brain dysconnectivity such as schizophrenia.
[Mh] Termos MeSH primário: Transtorno do Espectro Autista/terapia
Fator de Crescimento Insulin-Like I/metabolismo
Fator de Crescimento Insulin-Like I/uso terapêutico
Esquizofrenia/terapia
Membro 2 da Família 12 de Carreador de Soluto/metabolismo
[Mh] Termos MeSH secundário: Animais
Transtorno do Espectro Autista/complicações
Encéfalo/patologia
Bumetanida/uso terapêutico
Criança
Pré-Escolar
Cloretos/metabolismo
Endocanabinoides/metabolismo
Seres Humanos
Modelos Teóricos
Bainha de Mielina/química
Neurônios/metabolismo
Oligodendroglia/metabolismo
Ocitocina/metabolismo
Transtornos Psicóticos/complicações
Síndrome de Rett/tratamento farmacológico
Esquizofrenia/complicações
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chlorides); 0 (Endocannabinoids); 0 (IGF1 protein, human); 0 (SLC12A2 protein, human); 0 (Solute Carrier Family 12, Member 2); 0Y2S3XUQ5H (Bumetanide); 50-56-6 (Oxytocin); 67763-96-6 (Insulin-Like Growth Factor I)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170724
[Lr] Data última revisão:
170724
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170124
[St] Status:MEDLINE


  6 / 1827 MEDLINE  
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[PMID]:28074534
[Au] Autor:Kourdougli N; Pellegrino C; Renko JM; Khirug S; Chazal G; Kukko-Lukjanov TK; Lauri SE; Gaiarsa JL; Zhou L; Peret A; Castrén E; Tuominen RK; Crépel V; Rivera C
[Ad] Endereço:Inserm Unit 901, Inmed, Marseille, France.
[Ti] Título:Depolarizing γ-aminobutyric acid contributes to glutamatergic network rewiring in epilepsy.
[So] Source:Ann Neurol;81(2):251-265, 2017 Feb.
[Is] ISSN:1531-8249
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Rewiring of excitatory glutamatergic neuronal circuits is a major abnormality in epilepsy. Besides the rewiring of excitatory circuits, an abnormal depolarizing γ-aminobutyric acidergic (GABAergic) drive has been hypothesized to participate in the epileptogenic processes. However, a remaining clinically relevant question is whether early post-status epilepticus (SE) evoked chloride dysregulation is important for the remodeling of aberrant glutamatergic neuronal circuits. METHODS: Osmotic minipumps were used to infuse intracerebrally a specific inhibitor of depolarizing GABAergic transmission as well as a functionally blocking antibody toward the pan-neurotrophin receptor p75 (p75 ). The compounds were infused between 2 and 5 days after pilocarpine-induced SE. Immunohistochemistry for NKCC1, KCC2, and ectopic recurrent mossy fiber (rMF) sprouting as well as telemetric electroencephalographic and electrophysiological recordings were performed at day 5 and 2 months post-SE. RESULTS: Blockade of NKCC1 after SE with the specific inhibitor bumetanide restored NKCC1 and KCC2 expression, normalized chloride homeostasis, and significantly reduced the glutamatergic rMF sprouting within the dentate gyrus. This mechanism partially involves p75 signaling, as bumetanide application reduced SE-induced p75 expression and functional blockade of p75 decreased rMF sprouting. The early transient (3 days) post-SE infusion of bumetanide reduced rMF sprouting and recurrent seizures in the chronic epileptic phase. INTERPRETATION: Our findings show that early post-SE abnormal depolarizing GABA and p75 signaling fosters a long-lasting rearrangement of glutamatergic network that contributes to the epileptogenic process. This finding defines promising and novel targets to constrain reactive glutamatergic network rewiring in adult epilepsy. Ann Neurol 2017;81:251-265.
[Mh] Termos MeSH primário: Bumetanida/farmacologia
Fibras Musgosas Hipocampais/efeitos dos fármacos
Receptores de Fator de Crescimento Neural/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia
Membro 2 da Família 12 de Carreador de Soluto/efeitos dos fármacos
Estado Epiléptico/metabolismo
Simportadores/efeitos dos fármacos
Ácido gama-Aminobutírico/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Bumetanida/administração & dosagem
Masculino
Ratos
Ratos Wistar
Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem
Estado Epiléptico/tratamento farmacológico
Estado Epiléptico/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Nerve Growth Factor); 0 (Slc12a2 protein, rat); 0 (Sodium Potassium Chloride Symporter Inhibitors); 0 (Solute Carrier Family 12, Member 2); 0 (Symporters); 0 (TNFRSF16 protein, rat); 0 (potassium-chloride symporters); 0Y2S3XUQ5H (Bumetanide); 56-12-2 (gamma-Aminobutyric Acid)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170112
[St] Status:MEDLINE
[do] DOI:10.1002/ana.24870


  7 / 1827 MEDLINE  
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[PMID]:28057537
[Au] Autor:Yousuf MS; Zubkow K; Tenorio G; Kerr B
[Ad] Endereço:Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada.
[Ti] Título:The chloride co-transporters, NKCC1 and KCC2, in experimental autoimmune encephalomyelitis (EAE).
[So] Source:Neuroscience;344:178-186, 2017 Mar 06.
[Is] ISSN:1873-7544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Patients with multiple sclerosis (MS) often complain of neuropathic pain. According to the Gate Control Theory of Pain, spinal networks of GABAergic inhibitory interneurons are important in modulating nociceptive inputs from the periphery. Na+-K+-2Cl- co-transporter 1 (NKCC1) and K+-Cl- co-transporter 2 (KCC2) generally dictate the tone of GABA/glycine inhibition by regulating intracellular chloride concentrations. In this study, we investigated the role of NKCC1 and KCC2 in neuropathic pain observed in the animal model, experimental autoimmune encephalomyelitis (EAE), a commonly used model to study the pathophysiology of MS. Quantitative real-time polymerase chain reactions (qRT-PCR) analysis revealed no change in NKCC1 mRNA transcripts in dorsal root ganglia throughout EAE disease course. However, NKCC1 and KCC2 mRNA levels in the dorsal spinal cord were significantly reduced at disease onset and peak only to recover by the chronic time point. Similarly, Western blot data revealed a significant downregulation of NKCC1 and KCC2 in the dorsal spinal cord at disease onset but an upregulation of NKCC1 protein in the dorsal root ganglia at this time point. Treatment with bumetanide, an NKCC inhibitor, had no effect on mechanical hypersensitivity seen in mice with EAE even though it reversed the changes in the levels of NKCC1 and KCC2. We noted that bumetanide treatment, while effective at reversing the changes in monomeric KCC2 levels was ineffective at reversing the changes in oligomeric KCC2 which remained repressed. These results indicate that mechanical hypersensitivity in EAE is not mediated by altered levels of NKCC1.
[Mh] Termos MeSH primário: Encefalomielite Autoimune Experimental/metabolismo
Hiperalgesia/metabolismo
Neuralgia/metabolismo
Membro 2 da Família 12 de Carreador de Soluto/metabolismo
Medula Espinal/metabolismo
Simportadores/metabolismo
[Mh] Termos MeSH secundário: Animais
Bumetanida/farmacologia
Progressão da Doença
Encefalomielite Autoimune Experimental/tratamento farmacológico
Encefalomielite Autoimune Experimental/patologia
Feminino
Gânglios Espinais/efeitos dos fármacos
Gânglios Espinais/metabolismo
Gânglios Espinais/patologia
Expressão Gênica/efeitos dos fármacos
Hiperalgesia/tratamento farmacológico
Hiperalgesia/patologia
Camundongos Endogâmicos C57BL
Glicoproteína Mielina-Oligodendrócito
Neuralgia/tratamento farmacológico
Neuralgia/patologia
Fragmentos de Peptídeos
RNA Mensageiro/metabolismo
Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia
Medula Espinal/efeitos dos fármacos
Medula Espinal/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Myelin-Oligodendrocyte Glycoprotein); 0 (Peptide Fragments); 0 (RNA, Messenger); 0 (Slc12a2 protein, mouse); 0 (Sodium Potassium Chloride Symporter Inhibitors); 0 (Solute Carrier Family 12, Member 2); 0 (Symporters); 0 (myelin oligodendrocyte glycoprotein (35-55)); 0 (potassium-chloride symporters); 0Y2S3XUQ5H (Bumetanide)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170107
[St] Status:MEDLINE


  8 / 1827 MEDLINE  
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[PMID]:27926982
[Au] Autor:Lu KT; Huang TC; Tsai YH; Yang YL
[Ad] Endereço:Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
[Ti] Título:Transient receptor potential vanilloid type 4 channels mediate Na-K-Cl-co-transporter-induced brain edema after traumatic brain injury.
[So] Source:J Neurochem;140(5):718-727, 2017 Mar.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Na -K -2Cl co-transporter (NKCC1) plays an important role in traumatic brain injury (TBI)-induced brain edema via the MAPK cascade. The transient receptor potential vanilloid type 4 (TRPV4) channel participates in neurogenic inflammation, pain transmission, and edema. In this study, we investigated the relationship between NKCC1 and TRPV4 and the related signaling pathways in TBI-induced brain edema and neuronal damage. TBI was induced by the calibrated weight-drop device. Adult male Wistar rats were randomly assigned into sham and experimental groups for time-course studies of TRPV4 expression after TBI. Hippocampal TRPV4, NKCC1, MAPK, and PI-3K cascades were analyzed by western blot, and brain edema was also evaluated among the different groups. Expression of hippocampal TRPV4 peaked at 8 h after TBI, and phosphorylation of the MAPK cascade and Akt was significantly elevated. Administration of either the TRPV4 antagonist, RN1734, or NKCC1 antagonist, bumetanide, significantly attenuated TBI-induced brain edema through decreasing the phosphorylation of MEK, ERK, and Akt proteins. Bumetanide injection inhibited TRPV4 expression, which suggests NKCC1 activation is critical to TRPV4 activation. Our results showed that hippocampal NKCC1 activation increased TRPV4 expression after TBI and then induced severe brain edema and neuronal damage through activation of the MAPK cascade and Akt-related signaling pathway.
[Mh] Termos MeSH primário: Edema Encefálico/etiologia
Edema Encefálico/metabolismo
Lesões Encefálicas Traumáticas/complicações
Lesões Encefálicas Traumáticas/metabolismo
Membro 2 da Família 12 de Carreador de Soluto/metabolismo
Canais de Cátion TRPV/metabolismo
[Mh] Termos MeSH secundário: Animais
Água Corporal/metabolismo
Encéfalo/patologia
Edema Encefálico/tratamento farmacológico
Lesões Encefálicas Traumáticas/tratamento farmacológico
Bumetanida/administração & dosagem
Bumetanida/uso terapêutico
Hipocampo/metabolismo
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Masculino
Proteína Oncogênica v-akt/metabolismo
Ratos
Ratos Wistar
Sulfonamidas/administração & dosagem
Sulfonamidas/uso terapêutico
Canais de Cátion TRPV/antagonistas & inibidores
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RN 1734); 0 (Slc12a2 protein, rat); 0 (Solute Carrier Family 12, Member 2); 0 (Sulfonamides); 0 (TRPV Cation Channels); 0 (Trpv4 protein, rat); 0Y2S3XUQ5H (Bumetanide); EC 2.7.11.1 (Oncogene Protein v-akt)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170623
[Lr] Data última revisão:
170623
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161208
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.13920


  9 / 1827 MEDLINE  
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Texto completo
[PMID]:27871891
[Au] Autor:Santos LE; Rodrigues AM; Lopes MR; Costa VD; Scorza CA; Scorza FA; Cavalheiro EA; Almeida AG
[Ad] Endereço:Laboratório de Neurociência Experimental e Computacional, Departamento de Engenharia de Biossistemas, UFSJ, Brazil.
[Ti] Título:Long-term alcohol exposure elicits hippocampal nonsynaptic epileptiform activity changes associated with expression and functional changes in NKCC1, KCC2 co-transporters and Na /K -ATPase.
[So] Source:Neuroscience;340:530-541, 2017 Jan 06.
[Is] ISSN:1873-7544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nonsynaptic mechanism changes, particularly the enhancement of NKCC1 expression in the dentate gyrus (DG) after 4weeks of ethanol consumption, motivate the present work, in which rats were submitted to a period of chronic consumption (12weeks). Four groups of six animals (6-week-old male Wistar rats) were formed, including the control (C), ethanol 1 (E1), ethanol 2 (E2) and ethanol 3 (E3) groups. The rats in the E1, E2 and E3 groups were treated daily with a 30% v/v solution of ethanol, administered via oral gavage (1.0, 2.0 and 3.0g/kg, respectively). Nonsynaptic epileptiform activities (NEA) were induced by means of the zero-Ca and high-K model using hippocampal slices and were recorded in the DG. The presence of NKCC1, KCC2, α -Na /K -ATPase and GFAP immunoreactivity was analyzed. The results demonstrate that alcohol consumption changes NEA, and these changes are more prominent at the lower dosage. An increase in the DC shifts associated with epileptiform discharges was present with the low dose. This increase was correlated with the increment of NKCC1 expression. Confocal microscopy images indicate the NKCC1 increase was pronounced in the initial axonal segment of granule cells. The blockage of these cotransporters during NEA induction with bumetanide suppressed the DC shift increase and diminished all parameters of NEA that were quantified for all groups treated with ethanol. Therefore, the increase in NKCC1 expression and the effective activity of this cotransporter, which were observed in the treated groups, suggest that drugs that act for block NKCC1 represent promising strategies for diminishing the effects of alcohol damage on the brain.
[Mh] Termos MeSH primário: Transtornos Relacionados ao Uso de Álcool/metabolismo
Epilepsia/metabolismo
Hipocampo/efeitos dos fármacos
ATPase Trocadora de Sódio-Potássio/metabolismo
Membro 2 da Família 12 de Carreador de Soluto/metabolismo
Simportadores/metabolismo
[Mh] Termos MeSH secundário: Transtornos Relacionados ao Uso de Álcool/complicações
Transtornos Relacionados ao Uso de Álcool/patologia
Animais
Bumetanida/farmacologia
Depressores do Sistema Nervoso Central/toxicidade
Relação Dose-Resposta a Droga
Epilepsia/etiologia
Epilepsia/patologia
Etanol/toxicidade
Hipocampo/metabolismo
Hipocampo/patologia
Masculino
Potenciais da Membrana/efeitos dos fármacos
Potenciais da Membrana/fisiologia
Doenças Neurodegenerativas/etiologia
Doenças Neurodegenerativas/metabolismo
Doenças Neurodegenerativas/patologia
Ratos Wistar
Receptores de GABA-A/metabolismo
Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia
Técnicas de Cultura de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Central Nervous System Depressants); 0 (Receptors, GABA-A); 0 (Slc12a2 protein, rat); 0 (Sodium Potassium Chloride Symporter Inhibitors); 0 (Solute Carrier Family 12, Member 2); 0 (Symporters); 0 (potassium-chloride symporters); 0Y2S3XUQ5H (Bumetanide); 3K9958V90M (Ethanol); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161123
[St] Status:MEDLINE


  10 / 1827 MEDLINE  
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[PMID]:27800670
[Au] Autor:Rahmanzadeh R; Shahbazi A; Ardakani MK; Mehrabi S; Rahmanzade R; Joghataei MT
[Ad] Endereço:Division of Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
[Ti] Título:Lack of the effect of bumetanide, a selective NKCC1 inhibitor, in patients with schizophrenia: A double-blind randomized trial.
[So] Source:Psychiatry Clin Neurosci;71(1):72-73, 2017 Jan.
[Is] ISSN:1440-1819
[Cp] País de publicação:Australia
[La] Idioma:eng
[Mh] Termos MeSH primário: Bumetanida/farmacologia
Avaliação de Resultados (Cuidados de Saúde)
Esquizofrenia/tratamento farmacológico
Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia
[Mh] Termos MeSH secundário: Método Duplo-Cego
Seres Humanos
[Pt] Tipo de publicação:LETTER; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Sodium Potassium Chloride Symporter Inhibitors); 0Y2S3XUQ5H (Bumetanide)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170213
[Lr] Data última revisão:
170213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161102
[St] Status:MEDLINE
[do] DOI:10.1111/pcn.12475



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