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1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 823-827, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750825

RESUMO

Objective To study the characteristics of the expression of aquaporin-4 (AQP4) in the brains and astrocytes of rats with thermoplegia. Methods Sixty healthy male Sprague-Dawley rats weighing (250±30) g were randomly divided into control group and model group. The quiet exposure method with high temperature (40DegreesCelsius) and high humidity (70%) was used to make a typical rat model of thermoplegia to monitor rectal temperature and record onset time every 10 minutes. When the temperature of stressed rats reached 42.5 DegreesCelsius, it was regarded as onset time of the disease. The rats in both groups were placed at 26DegreesCelsius with humidity 60% later. After 5-hour observation and their behavior evaluation, the rats were killed and their brain tissues were taken for measuring the water content of the tissues. The astrocytes of the rats were cultured at 37DegreesCelsius and 41DegreesCelsius. AQP4 mRNA and protein expression were detected by reverse-transcription PCR and Western blot analysis. Results Compared with the control group, the expression of AQP4 mRNA and protein were significantly lower in the model group than in the control group. Conclusion High temperature may lead to the destruction of blood-brain barrier and the down-regulation of AQP4 mRNA and protein expression in experimental rats, which can induce the occurrence and development of cerebral edema in experimental rats.


Assuntos
Aquaporina 4/metabolismo , Barreira Hematoencefálica , Edema Encefálico/patologia , Golpe de Calor/patologia , Animais , Astrócitos , Encéfalo/metabolismo , Temperatura Alta , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
2.
Mymensingh Med J ; 28(3): 673-680, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31391443

RESUMO

Neuromyelitis Optica (NMO) previously known as Devic disease is inflammatory disorder of central nervous system characterized by severe immune mediated demyelination and axonal damage predominating targeting optic nerves and spinal cord leading to blindness and paralysis. The spectrum of the disease has expanded based on the specificity of the autoimmune response to the aquaporin-4 (AQP-4) water channel expressed on the end feet of astrocytes in the central nervous system. The coordinated immunological attack against aquaporin-4 is mediated by B & T cells, innate cells including neutrophils and eosinophils and complement system as well as pathogenic antibodies.


Assuntos
Debilidade Muscular , Neuromielite Óptica , Transtornos da Visão , Adulto , Aquaporina 4/metabolismo , Astrócitos , Sistema Nervoso Central , Humanos , Masculino , Debilidade Muscular/etiologia , Neuromielite Óptica/complicações , Neuromielite Óptica/diagnóstico , Medula Espinal , Transtornos da Visão/etiologia
3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(4): 480-483, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31109425

RESUMO

OBJECTIVE: To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway in the expression of aquaporin 4 (AQP4) in brain tissue of rats with cardiopulmonary resuscitation (CPR) during mild hypothermia. METHODS: Forty-eight healthy male Sprague-Dawley (SD) rats were divided into sham operation group, normal temperature group and mild hypothermia group according to random number table method, with 16 in each group. The rat model of cardiac arrest-cardiopulmonary resuscitation (CPR) was established by asphyxia method. The sham operation group only experienced venous catheterization and tracheal intubation. The mild hypothermia group was treated with hypothermia 0.5 hours after restore of spontaneous circulation (ROSC, maintaining esophageal temperature at 32-34 centigrade); the normal temperature group was treated at room temperature after ROSC (maintaining esophageal temperature at 36-38 centigrade). Brain tissue was harvested at 6 hours after ROSC, and histopathological changes were observed by hematoxylin-eosin (HE) staining. The water content of brain tissue was determined by dry-wet specific gravity method. The protein expressions of phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK), p38MAPK and AQP4 in brain tissue were determined by Western Blot. RESULTS: Compared with the sham operation group, the nerve cells in the normal temperature group were reduced in size, cytoplasmic loosening, nuclear pyknosis, and in apoptotic body formation, water content of brain tissue was significantly increased [(83.64±2.53)% vs. (77.95±0.94)%, P < 0.05], the protein expressions of p-p38MAPK, p38MAPK, AQP4 were significantly increased (p38MAPK/ß-actin: 1.010±0.217 vs. 0.427±0.090, p-p38MAPK/p38MAPK: 0.451±0.172 vs. 0.191±0.141, AQP4/ß-actin: 3.129±0.754 vs. 1.598±0.464, all P < 0.05). Compared with the normal temperature group, the degree of necrosis of nerve cells in the mild hypothermia group was reduced, the water content of brain tissue was significantly decreased [(80.49±2.05)% vs. (83.64±2.53)%, P < 0.05], the protein expression of p38MAPK, p-p38MAPK and AQP4 in brain tissue were significantly decreased (p38MAPK/ß-actin: 0.590±0.162 vs. 1.010±0.217, p-p38MAPK/p38MAPK: 0.298±0.076 vs. 0.451±0.172, AQP4/ß-actin: 2.061±0.340 vs. 3.129±0.754, all P < 0.05). CONCLUSIONS: Mild hypothermia may regulate the expression of AQP4 in brain tissue of CPR rats through p38MAPK signaling pathway, and reduce brain edema, thereby exerting brain protection.


Assuntos
Aquaporina 4/metabolismo , Edema Encefálico/prevenção & controle , Encéfalo/metabolismo , Hipotermia Induzida , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Reanimação Cardiopulmonar , Modelos Animais de Doenças , Parada Cardíaca/terapia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
4.
Biomed Res Int ; 2019: 6076571, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080825

RESUMO

Cerebral involvement especially brain abscess is life-threatening complication and major cause of death during Scedosporium apiospermum infection. However, little is known about pathogenesis of brain oedema associated with abscess in scedosporiosis. Experimental scedosporiosis was conducted in BALB/cMlac mice to characterize the presence of brain oedema, its type, and its related mechanisms focusing on aquaporin (AQP)-4, nuclear factor erythroid-2 related factor (Nrf-2), and tumor necrotic factor (TNF)-α. The results revealed that S. apiospermum infection induced severe inflammatory environment relevant to TNF-α expression and cytogenic oedema-associated brain abscess predominately in cerebrum of immunocompromised mice without voriconazole treatment reflecting to downregulation of AQP-4 in neighboring abscess areas and oedematous blood vessels. Downregulation of Nrf-2 in neuronal cells and myelin degeneration were significantly observed in nontreated mice. In summary, oxidative stress, severe inflammatory response, and space-occupying mass from abscess formation inducing tissue hypoxia might be the postulate causes of oedema induced by scedosporiosis.


Assuntos
Aquaporina 4/metabolismo , Abscesso Encefálico/imunologia , Abscesso Encefálico/metabolismo , Edema Encefálico/metabolismo , Micoses/imunologia , Fator 2 Relacionado a NF-E2/metabolismo , Scedosporium/patogenicidade , Animais , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Abscesso Encefálico/patologia , Regulação para Baixo , Feminino , Hipóxia , Hospedeiro Imunocomprometido/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Micoses/patologia , Bainha de Mielina , Estresse Oxidativo , Fator de Necrose Tumoral alfa/metabolismo , Voriconazol/farmacologia
6.
Cancer Invest ; 37(2): 67-72, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873889

RESUMO

There has been controversy about the presence and potential role of aquaporin-4 (AQP4) in glioblastoma (GBM). We analyzed tissue from 22 patients with newly-diagnosed GBM as well as matching tissue from 17 of these cases who underwent repeat resection for suspected recurrence and performed immunohistochemical analysis for AQP-4 expression. While some degree of AQP4 expression was detected in all 22 cases (39 samples), there was no clear relationship between staining pattern and disease status (active versus inactive GBM) between baseline and time of repeat biopsy. In addition, there was no clear relationship between AQP4 expression and degree of edema.


Assuntos
Aquaporina 4/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Adulto , Idoso , Biópsia , Neoplasias Encefálicas/patologia , Quimiorradioterapia/métodos , Progressão da Doença , Edema/metabolismo , Edema/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Glioblastoma/patologia , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
7.
Life Sci ; 221: 143-151, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30763576

RESUMO

The neurotoxicity of anesthetics on developing brain has been a focused issue for years. However, controversy exists between human and animal studies and surgery may be a potential reason for this. The discovery of glymphatic system, a pathway eliminating soluble substance from central nervous system (CNS), together with recent evidence that surgery-induced Aß increase contributes to cognition dysfunction made us rethink about the influence of anesthetics on cognitive function. The function of glymphatic system was proved to be enhanced by sleep and sedation, so we assumed that under clinical situation Aß1-40 whose accumulation played important role in cognitive dysfunction was increased by surgery and eliminated from CNS by glymphatic system. The function of glymphatic system is facilitated by aquaporin-4 (AQP-4), a water channel expressed in highly polarized manor in astrocytic endfeet, whose transcription is regulated by nuclear factor of activated T cells 5 (NFAT5). Our results suggest that under brief operation and sevoflurane exposure, surgery may be the main cause of Aß increase and sevoflurane increase the elimination of Aß by up-regulating AQP-4 which is the key component in glymphatic system.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Aquaporina 4/metabolismo , Fragmentos de Peptídeos/metabolismo , Sevoflurano/metabolismo , Peptídeos beta-Amiloides/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Encéfalo/metabolismo , Sistema Nervoso Central , Disfunção Cognitiva/metabolismo , Sistema Glinfático , Hipocampo/metabolismo , Masculino , Fatores de Transcrição NFATC/metabolismo , Fragmentos de Peptídeos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Sevoflurano/farmacologia , Ativação Transcricional , Regulação para Cima
8.
Cells ; 8(2)2019 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-30717425

RESUMO

The CNS plasma-membrane water channel aquaporin-4 (AQP4) is expressed as two major isoforms able to aggregate into supramolecular assemblies known as 'orthogonal arrays of particles' (OAPs). OAP subnanometric features are largely unknown mainly because a method for the expression, isolation, and crystallization of integral human OAPs has not been developed. Here, the human OAP-forming isoform M23-AQP4 was expressed in insect and mammalian cell lines and AQP4 and OAP features evaluated. Native size exclusion chromatography was employed to isolate and analyze authentically folded OAPs, and neuromyelitis optica (NMO)-specific sandwich ELISA was developed to test OAP-integrity. The results demonstrate that in insect cells most AQP4 remains intracellular and unfolded and that OAPs are largely disassembled after the detergent extraction step. In mammalian cells, AQP4 showed regular plasma membrane targeting and OAPs exhibited strong post-extraction stability. Starting from the mammalian cell expression system, we isolated authentically folded OAPs. Together these data suggest a new strategy for expressing and isolating integral recombinant human OAPs and providing new insights into the cell-type dependent OAP-assembly and post-extraction stability, potentially useful to design new approaches for structural and functional studies of OAP and for other plasma membrane proteins organized into supramolecular structures.


Assuntos
Aquaporina 4/química , Aquaporina 4/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Animais , Linhagem Celular , Membrana Celular/metabolismo , Humanos , Imunoglobulina G/metabolismo , Insetos , Mamíferos , Ligação Proteica , Transporte Proteico , Ratos , Relação Estrutura-Atividade
9.
Oncol Rep ; 41(3): 1707-1717, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30628716

RESUMO

Ischemic stroke is the main cause of brain injury and results in a high rate of morbidity, disability and mortality. In the present study, we aimed to determine whether miR­29a played a protective role in oxygen glucose deprivation (OGD) injury via regulation of the water channel protein aquaporin 4 (AQP4). Real­time PCR and western blotting were used to assess miR­29a levels and AQP4 protein levels, respectively. Apoptosis was detected by flow cytometry, and lactate dehydrogenase (LDH) was determined by enzyme­linked immunosorbent assay (ELISA). Overexpression of miR­29a was significantly downregulated in OGD­induced primary astrocytes, and transfection with a miR­29a mimic decreased LDH release and apoptosis, and improved cell health in OGD­induced astrocytes. AQP4 was the target of miR­29a, which suppressed AQP4 expression, and knockdown of AQP4 mitigated OGD­induced astrocyte injury. Furthermore, miR­29a regulated AQP4 expression in OGD­induced astrocytes. AQP4 exacerbated astrocyte injury following ischemic stroke, and knockdown of AQP4 protected OGD/RX­induced primary cultured astrocytes against injury. The effect of miR­29a inhibitor on primary astrocytes was lost following AQP4 knockdown. These findings indicated that miR­29a prevented astrocyte injury in vitro by inhibiting AQP4. Thus, miR­29a may protect primary cultured astrocytes after OGD­induced injury by targeting AQP4, and may be a potential therapeutic target for ischemic injury of astrocytes.


Assuntos
Aquaporina 4/genética , Isquemia Encefálica/genética , MicroRNAs/metabolismo , Acidente Vascular Cerebral/genética , Animais , Animais Recém-Nascidos , Aquaporina 4/metabolismo , Astrócitos , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Hipóxia Celular , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Técnicas de Silenciamento de Genes , Glucose/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Cultura Primária de Células , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Transdução de Sinais/genética , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Regulação para Cima
10.
Phys Chem Chem Phys ; 21(6): 3339-3346, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30688325

RESUMO

Electroporation is a matter of intensive ongoing research interest, and a much-neglected topic in trans-membrane proteins, particularly in view of such promising potential applications in medicine and biotechnology. In particular, selected such novel and exciting applications are predicated on controlling ionic conductivity through electro-pores. Here, we scrutinise the mechanisms of ions' electric conductivity, by means of structural rearrangements, through quasi-stable electro-pores through human-AQP4 as a well-representative prototype of trans-membrane ionic conduction, achieving exquisite control over ionic permeability manipulated by the application of intense static electric fields.


Assuntos
Aquaporina 4/química , Simulação de Dinâmica Molecular , Aquaporina 4/metabolismo , Condutividade Elétrica , Humanos , Íons/metabolismo , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Permeabilidade
11.
Brain Struct Funct ; 224(3): 1267-1278, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30684007

RESUMO

Astrocytes, the most abundant glial cells of the central nervous system are morphologically complex. They display numerous processes interacting with synapses and blood vessels. At the vascular interface, astrocyte endfeet-terminated processes almost entirely cover the blood vessel surface and participate to the gliovascular unit where important vascular properties of the brain are set such as the blood-brain barrier (BBB) integrity. How specific morphological and functional interactions between astrocytes and the vascular compartment develop has not been fully investigated. Here, we elaborated an original experimental strategy to study the postnatal development of astrocyte perivascular endfeet. Using purified gliovascular units, we focused on the postnatal expression of MLC1 and GlialCAM, two transmembrane proteins forming a complex enriched at the junction between mature astrocyte perivascular endfeet. We showed that MLC1 and GlialCAM were enriched and assembled into mature complexes in astrocyte perivascular endfeet between postnatal days 10 and 15, after the formation of astrocyte perivascular Aquaporin 4 water channels. These events correlated with the increased expression of Claudin-5 and P-gP, two endothelial-specific BBB components. These results illustrate for the first time that astrocyte perivascular endfeet differentiation is a complex and progressive process which correlates with BBB maturation. Moreover, our results suggest that maturation of the astrocyte endfeet MLC1/GlialCAM complex between postnatal days 10 and 15 might be a key event in the gliovascular unit maturation.


Assuntos
Astrócitos/fisiologia , Barreira Hematoencefálica/crescimento & desenvolvimento , Moléculas de Adesão Celular Neurônio-Glia/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas de Membrana/metabolismo , Complexos Multiproteicos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Aquaporina 4/metabolismo , Barreira Hematoencefálica/citologia , Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Moléculas de Adesão Celular Neurônio-Glia/genética , Claudina-5/metabolismo , Feminino , Técnicas In Vitro , Lectinas/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Proteínas do Tecido Nervoso/genética
12.
Cells ; 8(2)2019 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-30691235

RESUMO

Aquaporin-4 (AQP4) is a water channel expressed on astrocytic endfeet in the brain. The role of AQP4 has been studied in health and in a range of pathological conditions. Interest in AQP4 has increased since it was discovered to be the target antigen in the inflammatory autoimmune disease neuromyelitis optica spectrum disorder (NMOSD). Emerging data suggest that AQP4 may also be implicated in the glymphatic system and may be involved in the clearance of beta-amyloid in Alzheimer's disease (AD). In this review, we will describe the role of AQP4 in the adult and developing brain as well as its implication for disease.


Assuntos
Aquaporina 4/metabolismo , Encéfalo/metabolismo , Doença , Saúde , Animais , Encéfalo/embriologia , Desenvolvimento Embrionário , Sistema Glinfático/metabolismo , Humanos
13.
Psychopharmacology (Berl) ; 236(4): 1367-1384, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30607477

RESUMO

BACKGROUND: The glymphatic system has recently been proposed to function as a brain-wide macroscopic system for the clearance of potentially harmful molecules, such as amyloid beta (e.g., Aß), from the brain parenchyma. Previous literatures have established that the glymphatic function is dramatically suppressed by aging, traumatic brain injury, and some diseases. However, the effect of chronic stress on the glymphatic function and its underlying mechanism remains largely unknown. METHODS: Adult mice were randomly divided into four groups: chronic unpredictable mild stress (CUMS)-treated group, CUMS simultaneously treated with mifepristone (MFP) group, dexamethasone (DEX)-treated group, and control group. Stress response was observed by assessing the change of body weight, plasma corticosterone level, and behavior tests. The level of Aß42 in cerebral tissue was assessed by ELISA. The glymphatic function was determined by using fluorescence tracer injection. The expression and localization of aquaporin-4 (AQP4) were evaluated by immunohistochemistry and western blot. The transcription level of AQP4 and anchoring molecules was evaluated by real-time PCR. FINDINGS: Compared with control group, CUMS-treated mice exhibited the impairment of global glymphatic function especially in the anterior brain. This change was accompanied by the decreased expression and polarization of AQP4, reduced transcription of AQP4, agrin, laminin, and dystroglycan in the anterior cortex. Similarly, the glucocorticoid receptor (GR) agonist DEX exposure could reduce the glymphatic function and AQP4 expression. Moreover, the GR antagonist MFP treatment could significantly rescue the glymphatic function and reverse the expression and polarization of AQP4 impaired by CUMS. CONCLUSION: Chronic stress could impair the AQP4-mediated glymphatic transport in the brain through glucocorticoid signaling. Our results also suggest that GR antagonist could be beneficial to rescue the glymphatic function suppressed by chronic stress.


Assuntos
Aquaporina 4/metabolismo , Glucocorticoides/metabolismo , Sistema Glinfático/metabolismo , Transdução de Sinais/fisiologia , Estresse Psicológico/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dexametasona/toxicidade , Sistema Glinfático/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Receptores de Glucocorticoides/agonistas , Receptores de Glucocorticoides/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/induzido quimicamente , Estresse Psicológico/psicologia
14.
J Steroid Biochem Mol Biol ; 185: 90-102, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30031789

RESUMO

Treatment with progesterone limits brain damage after stroke. However, the cellular bases of the cerebroprotective effects of progesterone are not well documented. The aims of this study were to determine neural cells and functions that are affected by progesterone treatment and the role of neural progesterone receptors (PR) after stroke. Adult male PRNesCre mice, selectively lacking PR in the central nervous system, and their control PRloxP/loxP littermates were subjected to transient ischemia by middle cerebral artery occlusion (MCAO) for 30 min. Mice received either progesterone (8 mg/kg) or vehicle at 1-, 6- and 24- hrs post-MCAO and outcomes were analyzed at 48 h post-MCAO. In PRloxP/loxP mice, progesterone exerted multiple effects on different neural cell types, improved motor functional outcomes and reduced total infarct volumes. In the peri-infarct, progesterone increased the density of neurons (NeuN+ cells), of cells of the oligodendroglial lineage (Olig2+ cells) and of oligodendrocyte progenitors (OP, NG2+ cells). Progesterone decreased the density of activated astrocytes (GFAP+ cells) and reactive microglia (Iba1+ cells) coexpressing the mannose receptor type 1 CD206 marker. Progesterone also reduced the expression of aquaporin 4 (AQP4), the water channel involved in both edema formation and resorption. The beneficial effects of progesterone were not observed in PRNesCre mice. Our findings show that progesterone treatment exerts beneficial effects on neurons, oligodendroglial cells and neuroinflammatory responses via PR. These findings demonstrate that progesterone is a pleiotropic cerebroprotective agent and that neural PR represent a therapeutic target for stroke cerebroprotection.


Assuntos
Hipóxia-Isquemia Encefálica/prevenção & controle , Microglia/citologia , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Oligodendroglia/citologia , Progesterona/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Animais , Aquaporina 4/metabolismo , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Lectinas Tipo C/metabolismo , Masculino , Lectinas de Ligação a Manose/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/efeitos dos fármacos , Microglia/patologia , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/patologia , Receptores de Superfície Celular/metabolismo , Receptores de Progesterona/metabolismo
15.
J Neurol ; 266(5): 1280-1286, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30569382

RESUMO

Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is now recognised as a nosological entity with specific clinical and paraclinical features to aid early diagnosis. Although no age group is exempt, median age of onset is within the fourth decade of life, with optic neuritis being the most frequent presenting phenotype. Disease course can be either monophasic or relapsing, with subsequent relapses most commonly involving the optic nerve. Residual disability develops in 50-80% of patients, with transverse myelitis at onset being the most significant predictor of long-term outcome. Recent advances in MOG antibody testing offer improved sensitivity and specificity. To avoid misdiagnosis, MOG antibody testing should be undertaken in selected cases presenting clinical and paraclinical features that are felt to be in keeping with MOG-AD, using a validated cell-based assay. MRI characteristics can help in differentiating MOG-AD from other neuroinflammatory disorders, including multiple sclerosis and neuromyelitis optica. Cerebrospinal fluid oligoclonal bands are uncommon. Randomised control trials are limited, but observational open-label experience suggests a role for high-dose steroids and plasma exchange in the treatment of acute attacks, and for immunosuppressive therapies, such as steroids, oral immunosuppressants and rituximab as maintenance treatment.


Assuntos
Anticorpos/sangue , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica , Neurite Óptica , Aquaporina 4/metabolismo , Humanos , Neuromielite Óptica/sangue , Neuromielite Óptica/complicações , Neuromielite Óptica/terapia , Neurite Óptica/sangue , Neurite Óptica/complicações , Neurite Óptica/terapia , Troca Plasmática/métodos , Esteroides/uso terapêutico
16.
Invest Ophthalmol Vis Sci ; 59(15): 5876-5884, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30543343

RESUMO

Purpose: To determine whether cerebrospinal fluid (CSF) entry into the optic nerve is altered in glaucoma. Methods: Fluorescent 10-kDa dextran tracer was injected into the CSF of 2-month-old (n = 9) and 10-month-old DBA/2J glaucoma mice (n = 8) and age-matched controls (C57Bl/6; n = 8 each group). Intraocular pressure (IOP) was measured in all mice before tracer injection into CSF. Tracer distribution was assessed using confocal microscopy of optic nerve cross-sections of mice killed 1 hour after injection. Paravascular tracer distribution in the optic nerve was studied in relation to isolectin-stained blood vessels. Tracer intensity and cross-sectional area in the laminar optic nerve were quantitatively assessed in all four groups and statistically compared. Aquaporin 4 (AQP4) and retinal ganglion cell axonal phosphorylated neurofilament (pNF) were evaluated using immunofluorescence and confocal microscopy. Results: IOP was elevated in 10-month-old glaucoma mice compared with age-matched controls. One hour after tracer injection, controls showed abundant CSF tracer in the optic nerve subarachnoid space and within the nerve in paravascular spaces surrounding isolectin-labeled blood vessels. CSF tracer intensity and signal distribution in the optic nerve were significantly decreased in 10-month-old glaucoma mice compared with age-matched controls (P = 0.0008 and P = 0.0033, respectively). AQP4 immunoreactivity was similar in 10-month-old DBA and age-matched control mice. Half of the 10-month-old DBA mice (n = 4/8) showed a decrease in pNF immunoreactivity compared to controls. Altered pNF staining was seen only in DBA mice lacking CSF tracer at the laminar optic nerve (n = 4/5). Conclusions: This study provides the first evidence that CSF entry into the optic nerve is impaired in glaucoma. This finding points to a novel CSF-related mechanism that may help to understand optic nerve damage in glaucoma.


Assuntos
Líquido Cefalorraquidiano/metabolismo , Glaucoma/metabolismo , Doenças do Nervo Óptico/metabolismo , Animais , Aquaporina 4/metabolismo , Axônios/metabolismo , Axônios/patologia , Carbocianinas/metabolismo , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Corantes Fluorescentes/metabolismo , Glaucoma/patologia , Pressão Intraocular/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Microscopia Confocal , Proteínas de Neurofilamentos/metabolismo , Doenças do Nervo Óptico/patologia , Fosforilação , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia
17.
Sci Rep ; 8(1): 17954, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30560905

RESUMO

We performed multi-b and multi-diffusion-time diffusion-weighted magnetic resonance imaging on aquaporin-4-expressing (AQ) and -non-expressing (noAQ) cells, and demonstrated a clear difference between the signals from the two cell types. The data were interpreted using a two-compartment (intra and extracellular spaces) model including inter-compartmental exchange. It was also assumed that restricted diffusion of water molecules inside the cells leads to the intracellular diffusion coefficient being inversely proportional to the diffusion-time. Estimates of the water-exchange-times obtained with this model are compared to those measured using an independent optical imaging technique (coherent anti-Stokes Raman scattering imaging, CARS). For both techniques it was found that the exchange-time estimated for the noAQ cells was significantly longer than that for the AQ cells.


Assuntos
Aquaporina 4/metabolismo , Imagem de Difusão por Ressonância Magnética , Imagem Molecular , Análise Espectral Raman , Água/metabolismo , Aquaporina 4/genética , Imagem de Difusão por Ressonância Magnética/métodos , Espaço Extracelular/metabolismo , Espaço Intracelular/metabolismo , Modelos Teóricos , Imagem Molecular/métodos , Análise Espectral Raman/métodos
18.
Elife ; 72018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30561329

RESUMO

The glymphatic system is a brain-wide clearance pathway; its impairment contributes to the accumulation of amyloid-ß. Influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent failure to find an effect of Aqp4 knock-out (KO) on CSF and interstitial fluid (ISF) tracer transport, five groups re-examined the importance of AQP4 in glymphatic transport. We concur that CSF influx is higher in wild-type mice than in four different Aqp4 KO lines and in one line that lacks perivascular AQP4 (Snta1 KO). Meta-analysis of all studies demonstrated a significant decrease in tracer transport in KO mice and rats compared to controls. Meta-regression indicated that anesthesia, age, and tracer delivery explain the opposing results. We also report that intrastriatal injections suppress glymphatic function. This validates the role of AQP4 and shows that glymphatic studies must avoid the use of invasive procedures.


Assuntos
Aquaporina 4/metabolismo , Astrócitos/metabolismo , Encéfalo/metabolismo , Sistema Glinfático , Animais , Aquaporina 4/genética , Transporte Biológico , Líquido Cefalorraquidiano/metabolismo , Líquido Extracelular/metabolismo , Camundongos Knockout , Ratos
19.
Reprod Biomed Online ; 37(5): 601-612, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30539720

RESUMO

RESEARCH QUESTION: We recently reported that blocking of placental aquaporins (AQP) abrogates the apoptotic response of the trophoblast. As trophoblast apoptosis is exacerbated in pre-eclampsia, we hypothesized that changes in AQP in these placentae may trigger programmed cell death. We analysed AQP4 expression in pre-eclamptic placentae and its regulation by oxygen tension. DESIGN: AQP4 expression was studied in placentae from non-pathological and pre-eclamptic pregnancies by reverse transcription polymerase chain reaction (RT-PCR), Western blot, immunofluorescence and immunohistochemistry. Explants from non-pathological placentae were cultured in normoxia, hypoxia, hypoxia-reoxygenation and CoCl2. AQP4 expression was investigated by RT-PCR and Western blot. Hypoxia responsive elements sites on AQP4 promotor were investigated by in-silico analysis. AQP4 degradation was studied in the presence of proteosomal and lysosomal inhibitors. RESULTS: AQP4 protein expression was weakly detectable in pre-eclamptic placentae, but its mRNA was elevated compared with non-pathological placentae. In non-pathological explants cultured in hypoxia, AQP4 mRNA and protein were increased compared with placentae cultured in ambient oxygen but decreased after reoxygenation. Incubation with CoCl2, that stabilizes hypoxia inducible factor (HIF)-1α, also increased AQP4 levels. In-silico analysis showed three putative binding sites for HIF-1α in AQP4 promotor. CONCLUSIONS: Oxygen may regulate AQP4 expression in human placenta, possibly through HIF-1α. Therefore, the decrease in AQP4 throughout pregnancy, previously reported, is consistent with changes in HIF-1α, and suggests that AQP4 might have a crucial role during placentation. Therefore, the abnormal expression of AQP4 may be involved in the cause of pre-eclampsia, but it does not seem to take part in the apoptotic events.


Assuntos
Aquaporina 4/metabolismo , Oxigênio/farmacologia , Placenta/metabolismo , Apoptose , Western Blotting , Hipóxia Celular , Simulação por Computador , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Placenta/patologia , Placenta/fisiopatologia , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/metabolismo , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Ann Clin Lab Sci ; 48(4): 453-459, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30143486

RESUMO

The aim of the current study was to investigate the impact of methylprednisolone (MP) on the expression of Aquaporin 4 (AQP4) and spinal edema in rats with acute spinal cord injury (ASCI). Sprague-Dawley (SD) Wistar rats were randomly divided into the following groups: control (C), sham operation (S), ASCI, and MP-treated. After the ASCI model was induced and prepared, 30 mg/kg MP was injected via the tail vein, on postoperative days 1, 3, and 7. The Tarlov scoring method was used to evaluate the neurological outcome; spinal water content was measured using the wet/dry weight method; spinal pathological changes were evaluated by hematoxylin-eosin (HE) staining, and the expression of AQP4 was detected using Western blot. Compared to the S group, the motor nerve functional score (MNFS) was significantly lower in the ASCI group. Furthermore, their spinal water content and AQP4 expression was also significantly higher (P<0.05). Moreover, compared with the ASCI group, the MNFS, spinal water content, and AQP4 expression of the MP group was significantly lower (P<0.05). The ASCI groups showed severe, perivascular and neuronal edema, a reduction in the neuron number, shrinkage of the nuclei, necrosis of some spinal tissue white matter degeneration, and the formation of numerous cysts and vacuoles. In the MP group, the spinal gray matter and white matter had much clearer borders, with reduced bleeding range and karyopyknosis. Furthermore, this group showed improved perivascular and neuronal edema and an even distribution of intranuclear chromatins. MP inhibited spinal edema in rats with ASCI, which might be related to the reduced AQP4 expression in spinal tissues.


Assuntos
Aquaporina 4/metabolismo , Edema/tratamento farmacológico , Edema/metabolismo , Metilprednisolona/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/patologia , Doença Aguda , Animais , Edema/patologia , Edema/fisiopatologia , Masculino , Metilprednisolona/farmacologia , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Água
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