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1.
Neuromodulation ; 25(8): 1227-1239, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35382977

RESUMO

OBJECTIVES: Cerebral vasospasm is a severe and potentially lethal complication in patients with subarachnoid hemorrhage (SAH). Its pathogenesis is still not completely understood. The efficacy of current treatments, such as triple-H therapy or calcium channel blockers, is unsatisfactory, and a new therapy model would therefore be valuable. Electrical stimulation may have a considerable influence on cerebrovascular innervation. This systematic review gives an overview of the studies that have applied electrical stimulation in models of cerebral vasospasm. MATERIALS AND METHODS: We performed a systematic review of the literature, searching PubMed and Ovid Embase with the keywords "electric stimulation," "cerebral vasospasm," "subarachnoid hemorrhage," "sympathetic," and "parasympathetic." Additional papers were identified from the reference lists of the articles identified in the literature search. RESULTS: Increased cerebral blood flow (CBF) is a widely observed effect of spinal cord stimulation and sphenopalatine ganglion stimulation in models of physiological conditions or experimental cerebral vasospasm. Most studies were conducted in animals, 15 under physiological conditions and 11 in animals with SAH. Eight studies in humans were identified that examined the stimulation effect on CBF under physiological conditions. Only two studies looked at patients after SAH: one applied spinal cord stimulation (SCS) and the other transcutaneous electrical neurostimulation. Different mechanisms leading to stimulation-induced CBF increase that were discussed included "reversible functional sympathectomy," activation of brainstem vasomotor centers, involvement of central ascending pathways, release of neurohumoral factors, and interaction with sympathetic, parasympathetic, and trigeminal innervation. The results indicate that electrical stimulation is a promising procedure for prevention and treatment of cerebral vasospasm. CONCLUSION: Electrical stimulation, especially SCS and sphenopalatine ganglion stimulation, is a promising adjunct for existing therapies for vasospasm after SAH. Further experiments and prospective clinical studies are needed to establish its potential usefulness as a therapy or prevention option.


Assuntos
Gânglios Parassimpáticos , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Humanos , Animais , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/terapia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/terapia , Estudos Prospectivos , Estimulação Elétrica , Gânglios Parassimpáticos/patologia
2.
Genesis ; 59(12): e23453, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34664392

RESUMO

The vertebrate Six (Sine oculis homeobox) family of homeodomain transcription factors plays critical roles in the development of several organs. Six1 plays a central role in cranial placode development, including the precursor tissues of the inner ear, as well as other cranial sensory organs and the kidney. In humans, mutations in SIX1 underlie some cases of Branchio-oto-renal (BOR) syndrome, which is characterized by moderate-to-severe hearing loss. We utilized CRISPR/Cas9 technology to establish a six1 mutant line in Xenopus tropicalis that is available to the research community. We demonstrate that at larval stages, the six1-null animals show severe disruptions in gene expression of putative Six1 target genes in the otic vesicle, cranial ganglia, branchial arch, and neural tube. At tadpole stages, six1-null animals display dysmorphic Meckel's, ceratohyal, and otic capsule cartilage morphology. This mutant line will be of value for the study of the development of several organs as well as congenital syndromes that involve these tissues.


Assuntos
Síndrome Brânquio-Otorrenal/genética , Anormalidades Congênitas/genética , Perda Auditiva/genética , Proteínas de Homeodomínio/genética , Proteínas de Xenopus/genética , Animais , Região Branquial/crescimento & desenvolvimento , Região Branquial/patologia , Síndrome Brânquio-Otorrenal/fisiopatologia , Sistemas CRISPR-Cas/genética , Anormalidades Congênitas/patologia , Desenvolvimento Embrionário/genética , Gânglios Parassimpáticos/crescimento & desenvolvimento , Gânglios Parassimpáticos/patologia , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/genética , Perda Auditiva/fisiopatologia , Humanos , Tubo Neural/crescimento & desenvolvimento , Tubo Neural/patologia , Crânio/crescimento & desenvolvimento , Crânio/patologia , Fatores de Transcrição/genética , Xenopus/genética , Xenopus/crescimento & desenvolvimento
3.
PLoS One ; 15(11): e0242746, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33227035

RESUMO

Galanin is a neuropeptide widely expressed in central and peripheral nerves and is known to be engaged in neuronal responses to pathological changes. Stomach ulcerations are one of the most common gastrointestinal disorders. Impaired stomach function in peptic ulcer disease suggests changes in autonomic nerve reflexes controlled by the inferior vagal ganglion, resulting in stomach dysfunction. In this paper, changes in the galaninergic response of inferior vagal neurons to gastric ulceration in a pig model of the disease were analyzed based on the authors' previous studies. The study was performed on 24 animals (12 control and 12 experimental). Gastric ulcers were induced by submucosal injections of 40% acetic acid solution into stomach submucosa and bilateral inferior vagal ganglia were collected one week afterwards. The number of galanin-immunoreactive perikarya in each ganglion was counted to determine fold-changes between both groups of animals and Q-PCR was applied to verify the changes in relative expression level of mRNA encoding both galanin and its receptor subtypes: GalR1, GalR2, GalR3. The results revealed a 2.72-fold increase in the number of galanin-immunoreactive perikarya compared with the controls. Q-PCR revealed that all studied genes were expressed in examined ganglia in both groups of animals. Statistical analysis revealed a 4.63-fold increase in galanin and a 1.45-fold increase in GalR3 mRNA as compared with the controls. No differences were observed between the groups for GalR1 or GalR2. The current study confirmed changes in the galaninergic inferior vagal ganglion response to stomach ulcerations and demonstrated, for the first time, the expression of mRNA encoding all galanin receptor subtypes in the porcine inferior vagal ganglia.


Assuntos
Galanina/metabolismo , Gânglios Parassimpáticos/metabolismo , Receptores de Galanina/metabolismo , Úlcera Gástrica/metabolismo , Nervo Vago/metabolismo , Ácido Acético/toxicidade , Animais , Gânglios Parassimpáticos/patologia , RNA Mensageiro/metabolismo , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Suínos , Nervo Vago/patologia
5.
J Neurovirol ; 26(3): 391-403, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32301037

RESUMO

Herpes simplex virus type I (HSV-1) infection causes inflammation in the cornea known as herpes simplex virus keratitis (HSK), a common but serious corneal disease. It is not entirely clear whether the virus during recurring infection comes from the trigeminal ganglia or the eye tissue, including the retina and ciliary ganglion. Because the tree shrew is closely related to primates and tree shrew eye anatomic structures are similar to humans, we studied HSV-1 corneal infection in the tree shrew. We found that HSK symptoms closely mimic those found in human HSK showing typical punctiform and dendritic viral keratitis during the acute infection period. Following the HSV-specific lesions, complications such as stromal scarring, corneal thickening (primary infection), opacity, and neovascularization were observed. In the tree shrew model, following ocular inoculation, the cornea becomes infected, and viral protein can be detected using anti-HSV-1 antibodies in the epithelial layer and retina neuronal ganglion cells. The HSV-1 transcripts, ICP0, ICP4, and LAT can be detected at 3 days post-infection (dpi), peaking at 5 dpi. After 2 weeks, ICP4 and ICP0 transcripts are reduced to a basal level, but the Latency Associated Transcripts (LATs) continue to accumulate. Interestingly, after the acute infection, we still detected abundant active HSV-1 in tree shrew eyes. Further, we found HSV-1 persistent in the ciliary ganglion and cornea. These findings are discussed in support of the tree shrew as a non-human primate HSK model, which could be useful for mechanistic studies of HSK.


Assuntos
Córnea/virologia , Regulação Viral da Expressão Gênica , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Ceratite Herpética/virologia , Neovascularização Patológica/virologia , Animais , Córnea/patologia , Modelos Animais de Doenças , Feminino , Gânglios Parassimpáticos/patologia , Gânglios Parassimpáticos/virologia , Herpes Simples/patologia , Herpesvirus Humano 1/crescimento & desenvolvimento , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 1/patogenicidade , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Ceratite Herpética/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica/patologia , Neurônios/patologia , Neurônios/virologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Gânglio Trigeminal/patologia , Gânglio Trigeminal/virologia , Tupaia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Latência Viral
6.
Mol Cell Biochem ; 462(1-2): 1-10, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31468244

RESUMO

Diabetic cardiomyopathy is known to involve two forms of cardiac cell death: apoptosis and necrosis. However, it remains unknown whether hyperglycemia-induced apoptosis in the H9c2 cell culture system is inhibited by parasympathetic ganglionic neurons (PGN) derived exosomes (exos). We isolated PGN and sympathetic ganglionic neurons (SGN) from the right stellate ganglion in rats, and derived exos from these sources. H9c2 cells were divided into 4 groups: (1) Control, (2) H9c2 + Glucose (100 mmol/L), (3) H9c2 + Glucose + PGN-exos, and (4) H9c2 + Glucose + SGN-exos. We determined cell proliferation and viability with an MTT assay kit, and assessed apoptotic cell death with TUNEL staining and ELISA. Data were further confirmed by analyzing the presence of pro-apoptotic proteins Caspase-3 and Bax, and anti-apoptotic protein Bcl-2. Glucose exposed H9c2 cells significantly reduced cell viability, which was improved by PGN-exos, but not by SGN-exos. Furthermore, increased apoptosis in hyperglycemia in H9c2 cells was confirmed with TUNEL staining and cell death ELISA which demonstrated significantly (p < 0.05) reduction with PGN-exos treatment, but not with SGN-exos. Moreover, high expression of pro-apoptotic proteins Caspase-3 and Bax was reduced following treatment with PGN-exos; however, SGN-exos were unable to reduce the expression. Significantly reduced anti-apoptotic protein Bcl-2 following glucose treatment was improved with PGN-exos. Therefore, our data suggest that hyperglycemia induces apoptosis in H9c2 cells and decreases cell viability, and that PGN-exos are able to inhibit apoptosis, improve cell viability, and restore levels of anti-apoptotic protein Bcl-2.


Assuntos
Apoptose , Exossomos/metabolismo , Gânglios Parassimpáticos/patologia , Hiperglicemia/patologia , Miócitos Cardíacos/patologia , Neurônios/patologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Exossomos/efeitos dos fármacos , Glucose/toxicidade , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismo
7.
Turk Neurosurg ; 29(3): 362-368, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30649786

RESUMO

AIM: To understand possible mechanisms underlying lacrimal gland degeneration when facial nerve root ischemia induces pterygopalatine ganglion injury and subsequent dry eye in a rabbit model of subarachnoid hemorrhage. MATERIAL AND METHODS: Rabbits were divided into four groups: control, sham, moderate subarachnoid hemorrhage, and severe subarachnoid hemorrhage. Autologous blood recovered from the auricular artery was injected into the cisterna magna to induce subarachnoid hemorrhage in the two subarachnoid hemorrhage groups; animals were then monitored for dry eye development over 21 days before removal of their facial nerve roots, pterygopalatine ganglia, and lacrimal glands for immunohistochemical analyses. Neuronal viability in the pterygopalatine ganglia was measured; lacrimal gland vesicles were counted by stereological methods. RESULTS: The mean tear-filled vesicle number and lacrimal gland volumes significantly decreased with an increase in facial nerve root injury severity and damaged neuron numbers in the pterygopalatine ganglion. Increase in injury severity most significantly decreased the tear-filled vesicle numbers in the pterygopalatine ganglion. CONCLUSION: Subarachnoid hemorrhage degenerates facial nerve parasympathetic branches entering the pterygopalatine ganglion, and neuronal density in this ganglion may be correlated with tear secretion. Our data suggest that pterygopalatine ganglion degeneration following subarachnoid hemorrhage induces dry eye.


Assuntos
Síndromes do Olho Seco/patologia , Nervo Facial/irrigação sanguínea , Nervo Facial/patologia , Isquemia/patologia , Hemorragia Subaracnóidea/patologia , Animais , Contagem de Células , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/fisiopatologia , Gânglios Parassimpáticos/patologia , Gânglios Parassimpáticos/fisiopatologia , Isquemia/complicações , Isquemia/fisiopatologia , Coelhos , Distribuição Aleatória , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/fisiopatologia
8.
Am J Physiol Lung Cell Mol Physiol ; 315(2): L133-L148, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29631359

RESUMO

Mainstay therapeutics are ineffective in some people with asthma, suggesting a need for additional agents. In the current study, we used vagal ganglia transcriptome profiling and connectivity mapping to identify compounds beneficial for alleviating airway hyperreactivity (AHR). As a comparison, we also used previously published transcriptome data from sensitized mouse lungs and human asthmatic endobronchial biopsies. All transcriptomes revealed agents beneficial for mitigating AHR; however, only the vagal ganglia transcriptome identified agents used clinically to treat asthma (flunisolide, isoetarine). We also tested one compound identified by vagal ganglia transcriptome profiling that had not previously been linked to asthma and found that it had bronchodilator effects in both mouse and pig airways. These data suggest that transcriptome profiling of the vagal ganglia might be a novel strategy to identify potential asthma therapeutics.


Assuntos
Hiper-Reatividade Brônquica/metabolismo , Gânglios Parassimpáticos/metabolismo , Transcriptoma , Nervo Vago/metabolismo , Animais , Hiper-Reatividade Brônquica/genética , Hiper-Reatividade Brônquica/patologia , Hiper-Reatividade Brônquica/terapia , Gânglios Parassimpáticos/patologia , Masculino , Camundongos , Camundongos Knockout , Nervo Vago/patologia
9.
Turk Neurosurg ; 28(1): 48-55, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27593832

RESUMO

AIM: To investigate the relationship between neuron density of the superior cervical sympathetic ganglia and pupil diameter in subarachnoid hemorrhage. MATERIAL AND METHODS: This study was conducted on 22 rabbits; 5 for the baseline control group, 5 for the SHAM group and 12 for the study group. Pupil diameters were measured via sunlight and ocular tomography on day 1 as the control values. Pupil diameters were re-measured after injecting 0.5 cc saline to the SHAM group, and autologous arterial blood into the cisterna magna of the study group. After 3 weeks, the brain, superior cervical sympathetic ganglia and ciliary ganglia were extracted with peripheral tissues bilaterally and examined histopathologically. Pupil diameters were compared with neuron densities of the sympathetic ganglia and ciliary ganglia which were examined using stereological methods. RESULTS: Baseline values were; normal pupil diameter 7.180±620 ?m and mean neuron density of the superior cervical sympathetic ganglia 6.321±510/mm3, degenerated neuron density of ciliary ganglia was 5±2/mm3 after histopathological examination in the control group. These values were measured as 6.850±578 ?m, 5.950±340/mm3 and 123±39/mm3 in the SHAM group and 9.910±840 ?m, 7.950±764/mm3 and 650±98/mm3 in the study group. A linear relationship was determined between neuron density of the superior cervical sympathetic ganglia and pupil diameters (p < 0.005). Degenerated ciliary ganglia neuron density had an inverse effect on pupil diameters in all groups (p < 0.0001). CONCLUSION: Highly degenerated neuron density of the ciliary ganglion is not responsible for pupil dilatation owing to parasympathetic pupilloconstrictor palsy, but high neuron density of the pupillodilatatory superior cervical sympathetic ganglia should be considered an important factor for pupil dilatation.


Assuntos
Modelos Animais de Doenças , Midríase/patologia , Pupila/fisiologia , Hemorragia Subaracnóidea/patologia , Gânglio Cervical Superior/patologia , Animais , Cisterna Magna/patologia , Cisterna Magna/fisiopatologia , Gânglios Parassimpáticos/patologia , Gânglios Parassimpáticos/fisiopatologia , Masculino , Midríase/fisiopatologia , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Neurônios/patologia , Neurônios/fisiologia , Coelhos , Hemorragia Subaracnóidea/fisiopatologia , Gânglio Cervical Superior/fisiopatologia
10.
Headache ; 57 Suppl 1: 14-28, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28387016

RESUMO

OBJECTIVE: To describe the history of and available data on sphenopalatine ganglion (SPG) neuromodulation in the treatment of headache up to the present. BACKGROUND: The SPG has been a therapeutic target to treat primary headache disorders for over 100 years. Multiple destructive lesions have also been tried with variable rate and duration of success. Neurostimulation of the SPG for cluster headache was first described in 2007. METHODS: This is not a systematic review. The authors review the anatomy and pathophysiology of the SPG and cluster headache and the important clinical trials, relating a history of how SPG neuromodulation reached the current state of approval in the European Union (EU) and pivotal registration study for cluster headache in the US. RESULTS: The EU approved SPG stimulation for cluster headache with a CE Mark in February of 2012. Since then, several EU countries have elected to reimburse implantation for cluster headache, and over 300 patients have been implanted worldwide. CONCLUSIONS: Success rates for implanted SPG neuromodulation in the experimental phase of the European randomized controlled trial, in the open label extension trial, and in the registry of patients implanted outside of the trial remain at about two-thirds of patients implanted being responders, defined as being able to terminate at least 50% of attacks or having at least a 50% decrease in attack frequency or both. A US pivotal registration study is underway to confirm these results and obtain FDA approval for this treatment for cluster headache patients. Further studies in migraine are also underway.


Assuntos
Cefaleia Histamínica/fisiopatologia , Cefaleia Histamínica/terapia , Terapia por Estimulação Elétrica/métodos , Gânglios Parassimpáticos/fisiopatologia , Animais , Cefaleia Histamínica/patologia , Terapia por Estimulação Elétrica/efeitos adversos , Terapia por Estimulação Elétrica/instrumentação , Gânglios Parassimpáticos/patologia , Humanos , Neuroestimuladores Implantáveis/efeitos adversos
11.
Proc Natl Acad Sci U S A ; 113(44): E6840-E6848, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27791112

RESUMO

Neurons of the Statoacoustic Ganglion (SAG), which innervate the inner ear, originate as neuroblasts in the floor of the otic vesicle and subsequently delaminate and migrate toward the hindbrain before completing differentiation. In all vertebrates, locally expressed Fgf initiates SAG development by inducing expression of Neurogenin1 (Ngn1) in the floor of the otic vesicle. However, not all Ngn1-positive cells undergo delamination, nor has the mechanism controlling SAG delamination been elucidated. Here we report that Goosecoid (Gsc), best known for regulating cellular dynamics in the Spemann organizer, regulates delamination of neuroblasts in the otic vesicle. In zebrafish, Fgf coregulates expression of Gsc and Ngn1 in partially overlapping domains, with delamination occurring primarily in the zone of overlap. Loss of Gsc severely inhibits delamination, whereas overexpression of Gsc greatly increases delamination. Comisexpression of Ngn1 and Gsc induces ectopic delamination of some cells from the medial wall of the otic vesicle but with a low incidence, suggesting the action of a local inhibitor. The medial marker Pax2a is required to restrict the domain of gsc expression, and misexpression of Pax2a is sufficient to block delamination and fully suppress the effects of Gsc The opposing activities of Gsc and Pax2a correlate with repression or up-regulation, respectively, of E-cadherin (cdh1). These data resolve a genetic mechanism controlling delamination of otic neuroblasts. The data also elucidate a developmental role for Gsc consistent with a general function in promoting epithelial-to-mesenchymal transition (EMT).


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Gânglios Parassimpáticos/crescimento & desenvolvimento , Gânglios Parassimpáticos/metabolismo , Proteína Goosecoid/genética , Proteína Goosecoid/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurogênese/fisiologia , Organizadores Embrionários , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Animais , Caderinas/metabolismo , Diferenciação Celular/genética , Orelha Interna/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Gânglios Parassimpáticos/patologia , Gastrulação , Regulação da Expressão Gênica no Desenvolvimento , Homologia de Genes , Imuno-Histoquímica , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Neurogênese/genética , Organizadores Embrionários/patologia , Fator de Transcrição PAX2/metabolismo , Transdução de Sinais , Regulação para Cima , Nervo Vestibulococlear/crescimento & desenvolvimento , Nervo Vestibulococlear/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
12.
J Headache Pain ; 17(1): 78, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27587062

RESUMO

BACKGROUND: Migraine and Cluster Headache (CH) are two primary headaches with severe disease burden. The disease expression and the mechanisms involved are poorly known. In some attacks of migraine and in most attacks of CH, there is a release of vasoactive intestinal peptide (VIP) originating from parasympathetic cranial ganglia such as the sphenopalatine ganglion (SPG). Patients suffering from these diseases are often deprived of effective drugs. The aim of the study was to examine the localization of the botulinum toxin receptor element synaptic vesicle glycoprotein 2A (SV-2A) and the vesicular docking protein synaptosomal-associated protein 25 (SNAP25) in human and rat SPG. Additionally the expression of the neurotransmitters pituitary adenylate cyclase activating polypeptide (PACAP-38), nitric oxide synthase (nNOS), VIP and 5-hydroxttryptamine subtype receptors (5-HT1B,1D,1F) were examined. METHODS: SPG from adult male rats and from humans, the later removed at autopsy, were prepared for immunohistochemistry using specific antibodies against neurotransmitters, 5-HT1B,1D,1F receptors, and botulinum toxin receptor elements. RESULTS: We found that the selected neurotransmitters and 5-HT receptors were expressed in rat and human SPG. In addition, we found SV2-A and SNAP25 expression in both rat and human SPG. We report that all three 5-HT receptors studied occur in neurons and satellite glial cells (SGCs) of the SPG. 5-HT1B receptors were in addition found in the walls of intraganglionic blood vessels. CONCLUSIONS: Recent focus on the SPG has emphasized the role of parasympathetic mechanisms in the pathophysiology of mainly CH. The development of next generation's drugs and treatment of cranial parasympathetic symptoms, mediated through the SPG, can be modulated by treatment with BoNT-A and 5-HT receptor agonists.


Assuntos
Cefaleia Histamínica/patologia , Gânglios Parassimpáticos/patologia , Transtornos de Enxaqueca/patologia , Neurônios/metabolismo , Adulto , Animais , Cadáver , Cefaleia Histamínica/metabolismo , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Gânglios Parassimpáticos/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Transtornos de Enxaqueca/metabolismo , Terapia de Alvo Molecular , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Ratos , Ratos Sprague-Dawley , Ratos Wistar
13.
Neurosci Lett ; 630: 93-100, 2016 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-27436478

RESUMO

BACKGROUND: Photophobia is defined as a painful psychosomatic discomfort triggered by intense light flow through the pupils to the brain, but the exact mechanism through which photophobia is induced by subarachnoid hemorrhage (SAH) is not well understood. In this study, we aimed to investigate whether there was any relationship between the mydriasis induced by the degeneration of the ciliary ganglion (CG) and photophobia in instances of SAH. MATERIALS AND METHODS: Five of a total of 25 rabbits were used as the intact control group; five were used in the sham-operated control group; and the remaining 15 were used as the SAH group, which was created by injecting autologous blood into their cisterna magna. All animals were examined daily for 20days to evaluate their level of photophobia, after which their brains, CGs and superior cervical ganglia (SCGs) were extracted bilaterally. The densities of normal and degenerated neurons in these ganglia were examined by stereological methods. RESULTS: In SAH animals with a high photophobia score, the mean pupil diameter and density of degenerated neurons density in the CG were greater than in cases with a low photophobia score (p<0.05). Further analysis revealed that the increase in the density of degenerated neurons in the CG following SAH resulted in the paralysis of the parasympathetic pathway of the pupillary muscles and mydriasis, which facilitates the excessive transfer of light to the brain and photophobia. CONCLUSION: Our findings indicate that SAH results in a high density of degenerated neurons in the CG, which induces mydriasis and is an important factor in the onset of photophobia. This phenomenon is likely due to more light energy being transferred through mydriatic pupils to the brain, resulting in vasospasm of the supplying arteries.


Assuntos
Gânglios Parassimpáticos/patologia , Midríase/patologia , Fotofobia/patologia , Fotofobia/fisiopatologia , Hemorragia Subaracnóidea/complicações , Animais , Modelos Animais de Doenças , Midríase/etiologia , Nervo Oculomotor/patologia , Fotofobia/etiologia , Coelhos
14.
Exp Neurol ; 285(Pt B): 136-146, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26655672

RESUMO

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)+ neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-ß-hydroxylase (DBH)- and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH+ neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH+ neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH+ cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH+ neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI.


Assuntos
Dopamina/metabolismo , Reflexo/fisiologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Animais , Animais Recém-Nascidos , Colina O-Acetiltransferase/metabolismo , Modelos Animais de Doenças , Dopamina/análogos & derivados , Dopaminérgicos/farmacologia , Ensaio de Imunoadsorção Enzimática , Feminino , Gânglios Parassimpáticos/patologia , Gânglios Simpáticos/patologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Herpesvirus Suídeo 1/genética , Herpesvirus Suídeo 1/metabolismo , Neurônios/metabolismo , Oxidopamina/toxicidade , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Ratos Wistar , Traumatismos da Medula Espinal/induzido quimicamente , Estilbamidinas/farmacocinética , Tiocarbamatos/metabolismo , Transdução Genética , Tirosina 3-Mono-Oxigenase/metabolismo , Bexiga Urinária/inervação , Bexiga Urinária/fisiopatologia
15.
Bull Exp Biol Med ; 159(5): 670-4, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26463057

RESUMO

Structural alterations in the central autonomic nuclei (dorsal vagal complex and intermediolateral nucleus) of the centrifuged random-bred male rats subjected to +Gz loads were examined. Acute exposure to gravitational loads predominantly produced the reactive changes in these nuclei, while persistently repeated regular loads resulted in cumulation of the destructive alterations. The structural perturbations in the central autonomic nuclei can disturb the autonomic regulation of physiological functions. The character of such disturbances is partially determined by the peculiarities in structural organization of these nuclei.


Assuntos
Área Postrema/ultraestrutura , Gânglios Parassimpáticos/ultraestrutura , Hipergravidade , Neurônios/ultraestrutura , Corno Lateral da Medula Espinal/ultraestrutura , Animais , Área Postrema/irrigação sanguínea , Área Postrema/patologia , Centrifugação , Gânglios Parassimpáticos/irrigação sanguínea , Gânglios Parassimpáticos/patologia , Masculino , Microscopia Eletrônica de Transmissão , Microtomia , Neurônios/patologia , Ratos , Ratos Wistar , Corno Lateral da Medula Espinal/irrigação sanguínea , Corno Lateral da Medula Espinal/patologia
16.
Turk Neurosurg ; 25(4): 519-25, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26242326

RESUMO

AIM: Pulmonary arteries are mainly innervated by sympathetic vasoconstrictor and parasympathetic vasodilatory fibers. We examined whether there is a relationship between the neuron densities of hilar parasympathetic ganglia and pulmonary vasospasm in subarachnoid hemorrhage (SAH). MATERIAL AND METHODS: Twenty-four rabbits were divided into two groups: control (n=8) and SAH (n=16). The animals were observed for 20 days following experimental SAH. The number of hilar parasympathetic ganglia and their neuron densities were determined. Proportion of pulmonary artery ring surface to lumen surface values was accepted as vasospasm index (VSI). Neuron densities of the hilar ganglia and VSI values were compared statistically. RESULTS: Animals in the SAH group experienced either mild (n=6) or severe (n=10) pulmonary artery vasospasm. In the control group, the mean VSI of pulmonary arteries was 0.777±0.048 and the hilar ganglion neuron density was estimated as 12.100±2.010/mm < sup > 3 < /sup > . In SAH animals with mild vasospasm, VSI=1.148±0.090 and neuron density was estimated as 10.110±1.430/mm < sup > 3 < /sup > ; in animals with severe vasospasm, VSI=1.500±0.120 and neuron density was estimated as 7.340±990/mm < sup > 3 < /sup > . CONCLUSION: There was an inverse correlation between quantity and neuron density of hilar ganglia and vasospasm index value. The low numbers and low density of hilar parasympathetic ganglia may be responsible for the more severe artery vasospasm in SAH.


Assuntos
Gânglios Parassimpáticos/patologia , Artéria Pulmonar/patologia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/patologia , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/patologia , Animais , Contagem de Células , Gânglios Parassimpáticos/citologia , Hemodinâmica , Estimativa de Kaplan-Meier , Meninges/patologia , Neurônios , Coelhos , Testes de Função Respiratória , Análise de Sobrevida
17.
PLoS One ; 9(6): e99944, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24945437

RESUMO

Hirschsprung disease-associated enterocolitis (HAEC) leads to significant mortality and morbidity, but its pathogenesis remains unknown. Changes in the colonic epithelium related to goblet cells and the luminal mucus layer have been postulated to play a key role. Here we show that the colonic epithelium of both aganglionic and ganglionic segments are altered in patients and in mice with Hirschsprung disease (HSCR). Structurally, goblet cells were altered with increased goblet cell number and reduced intracellular mucins in the distal colon of biopsies from patients with HSCR. Endothelin receptor B (Ednrb) mutant mice showed increased goblet cell number and size and increased cell proliferation compared to wild-type mice in aganglionic segments, and reduced goblet cell size and number in ganglionic segments. Functionally, compared to littermates, Ednrb-/- mice showed increased transepithelial resistance, reduced stool water content and similar chloride secretion in the distal colon. Transcript levels of goblet cell differentiation factors SPDEF and Math1 were increased in the distal colon of Ednrb-/- mice. Both distal colon from Ednrb mice and biopsies from HSCR patients showed reduced Muc4 expression as compared to controls, but similar expression of Muc2. Particle tracking studies showed that mucus from Ednrb-/- mice provided a more significant barrier to diffusion of 200 nm nanoparticles as compared to wild-type mice. These results suggest that aganglionosis is associated with increased goblet cell proliferation and differentiation and subsequent altered surface mucus properties, prior to the development of inflammation in the distal colon epithelium. Restoration of normal goblet cell function and mucus layer properties in the colonic epithelium may represent a therapeutic strategy for prevention of HAEC.


Assuntos
Colo/patologia , Gânglios Parassimpáticos/patologia , Células Caliciformes/patologia , Doença de Hirschsprung/patologia , Muco/metabolismo , Receptor de Endotelina B/genética , Receptores de Endotelina/genética , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Transporte Biológico , Contagem de Células , Diferenciação Celular , Tamanho Celular , Colo/metabolismo , Fezes/química , Deleção de Genes , Regulação da Expressão Gênica , Células Caliciformes/metabolismo , Doença de Hirschsprung/genética , Doença de Hirschsprung/metabolismo , Humanos , Camundongos , Camundongos Knockout , Mucina-2/genética , Mucina-2/metabolismo , Mucina-4/genética , Mucina-4/metabolismo , Nanopartículas/metabolismo , Técnicas de Patch-Clamp , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , Receptor de Endotelina B/deficiência , Receptores de Endotelina/metabolismo
18.
Chin J Integr Med ; 18(3): 214-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22466947

RESUMO

OBJECTIVE: To observe the efficacy and safety of sphenopalatine ganglion needling in treating patients with primary trigeminal neuralgia (PTN) of Liver (Gan)-yang upsurge syndrome (LYUS) type. METHODS: Sixty-five PTN patients of LYUS type were assigned by a random number table to two groups and treated by deep-needling (33 patients, DN group) and superficial-needling (32 patients, SN group), respectively. The main-acupoint used for both groups was Xiaguan (ST7) of affected side, on which needle was deeply inserted to reach spheno-palatine ganglion in the DN group, but was inserted conventionally in the SN group; the auxiliary acupoints used were the local points Cuanzhu (BL2), Sibai (ST2), Chengjiang (CV24) of affected side, as well as the remote points, bilateral Hegu (LI4) and Taichong (LR3). The needling was implemented every other day, with electric stimulation applied to all the punctured acupoints for 30 min, 10 days treatment as one therapeutic course. Each patient received 2 courses of needling with 1 week interval in between. The clinical efficacy, pain control and adverse reaction were evaluated and compared after the treatment. RESULTS: Rank-sum test showed that the efficacy in the DN group was significantly better than that in the SN group (Z =2.30, P=0.021); the pain was alleviated in both groups in frequency, intensity and sustained time (evaluated by visual analogue scale) significantly (P<0.01), but deep needling showed a superiority over superficial needling in reducing the frequency and intensity of episode (Z=9.55, Z=5.50, both P=0.00). No adverse reaction occurred during the treatment course of both groups. CONCLUSION: Spheno-palatine ganglion needling is highly effective, safe and reliable for the treatment of PTN.


Assuntos
Gânglios Parassimpáticos/patologia , Fígado/patologia , Agulhas , Neuralgia do Trigêmeo/terapia , Terapia por Acupuntura/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agulhas/efeitos adversos , Dor/complicações , Síndrome , Resultado do Tratamento , Neuralgia do Trigêmeo/complicações
19.
Biochem Cell Biol ; 88(4): 747-55, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20651848

RESUMO

The cystic fibrosis transmembrane conductance regulator (CFTR) is an important protein that acts as a chloride channel and regulates many physiological functions, including salt transport and fluid flow. Mutations in the gene encoding the CFTR protein cause cystic fibrosis. CFTR is expressed in the epithelial cells of the lungs, pancreas, intestines, and other organs. In the peripheral and central nervous system, CFTR expression has been detected in the neurons of rat brains, ganglion cells of rat hearts, human hypothalamus, human spinal cord, and human spinal and sympathetic ganglia. However, CFTR has not been identified in other parts of the nervous system. In this study, we used immunohistochemistry, in situ hybridization, and laser-assisted microdissection (LMD) followed by reverse transcriptase (RT) PCR to identify CFTR proteins and messenger RNA in human and rat paracervical ganglion cells. CFTR and its gene expression were both detected in paracervical ganglion cells, a finding that might link this important protein to the neuronal regulation of female urogenital function. These findings could provide new insights into the symptoms related to the reproductive system frequently observed in female cystic fibrosis patients.


Assuntos
Colo do Útero/inervação , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Gânglios Parassimpáticos/metabolismo , Adulto , Animais , Colo do Útero/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Feminino , Gânglios Parassimpáticos/patologia , Expressão Gênica , Humanos , Imuno-Histoquímica , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual , Adulto Jovem
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