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2.
PLoS One ; 15(5): e0227463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469979

RESUMO

Disruption of blood-brain barrier integrity and dramatic failure of brain ion homeostasis including fluctuations of pH occurs during cortical spreading depression (CSD) events associated with several neurological disorders, including migraine with aura, traumatic brain injury and stroke. NHE1 is the primary regulator of pH in the central nervous system. The goal of the current study was to investigate the role of sodium-hydrogen exchanger type 1 (NHE1) in blood brain barrier (BBB) integrity during CSD events and the contributions of this antiporter on xenobiotic uptake. Using immortalized cell lines, pharmacologic inhibition and genetic knockdown of NHE1 mitigated the paracellular uptake of radiolabeled sucrose implicating functional NHE1 in BBB maintenance. In contrast, loss of functional NHE1 in endothelial cells facilitated uptake of the anti-migraine therapeutic, sumatriptan. In female rats, cortical KCl but not aCSF selectively reduced total expression of NHE1 in cortex and PAG but increased expression in trigeminal ganglia; no changes were seen in trigeminal nucleus caudalis. Thus, in vitro observations may have a significance in vivo to increase brain sumatriptan levels. Pharmacological inhibition of NHE1 prior to cortical manipulations enhanced the efficacy of sumatriptan at early time-points but induced facial sensitivity alone. Overall, our results suggest that dysregulation of NHE1 contributes to breaches in BBB integrity, drug penetrance, and the behavioral sensitivity to the antimigraine agent, sumatriptan.


Assuntos
Barreira Hematoencefálica/metabolismo , Depressão Alastrante da Atividade Elétrica Cortical/genética , Trocador 1 de Sódio-Hidrogênio/genética , Sumatriptana/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/patologia , Depressão Alastrante da Atividade Elétrica Cortical/efeitos dos fármacos , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Injeções Intraperitoneais , Enxaqueca com Aura/tratamento farmacológico , Enxaqueca com Aura/genética , Enxaqueca com Aura/patologia , Ratos , Trocador 1 de Sódio-Hidrogênio/antagonistas & inibidores , Gânglio Trigeminal/efeitos dos fármacos , Gânglio Trigeminal/patologia
3.
PLoS One ; 15(3): e0230870, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32226020

RESUMO

When herpes simplex virus 1 (HSV-1) infection is initiated in the ocular, nasal, or oral cavity, sensory neurons within trigeminal ganglia (TG) become infected. Following a burst of viral transcription in TG neurons, lytic cycle viral genes are suppressed and latency is established. The latency-associated transcript (LAT) is the only viral gene abundantly expressed during latency, and LAT expression is important for the latency-reactivation cycle. Reactivation from latency is required for virus transmission and recurrent disease, including encephalitis. The Wnt/ß-catenin signaling pathway is differentially expressed in TG during the bovine herpesvirus 1 latency-reactivation cycle. Hence, we hypothesized HSV-1 regulates the Wnt/ß-catenin pathway and promotes maintenance of latency because this pathway enhances neuronal survival and axonal repair. New studies revealed ß-catenin was expressed in significantly more TG neurons during latency compared to TG from uninfected mice or mice latently infected with a LAT-/- mutant virus. When TG explants were incubated with media containing dexamethasone to stimulate reactivation, significantly fewer ß-catenin+ TG neurons were detected. Conversely, TG explants from uninfected mice or mice latently infected with a LAT-/- mutant increased the number of ß-catenin+ TG neurons in the presence of DEX relative to samples not treated with DEX. Impairing Wnt signaling with small molecule antagonists reduced virus shedding during explant-induced reactivation. These studies suggested ß-catenin was differentially expressed during the latency-reactivation cycle, in part due to LAT expression.


Assuntos
Regulação da Expressão Gênica , Herpesvirus Humano 1/fisiologia , Neurônios/metabolismo , Neurônios/virologia , Gânglio Trigeminal/citologia , Ativação Viral , beta Catenina/metabolismo , Animais , Feminino , Camundongos , Via de Sinalização Wnt
4.
J Oral Sci ; 62(2): 126-130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32224566

RESUMO

Dental pulp is densely innervated by sensory afferents that are primarily involved in nociception. Elucidating the type and properties of these afferents and their distribution patterns within the dental pulp is crucial for understanding the mechanisms of acute dental pain and dental hypersensitivity. Recent studies on the release of the transmitter glutamate and the expression of glutamate receptors and vesicular glutamate transporters (VGLUT) in the pulpal axons and trigeminal ganglion (TG) have suggested the possibility of a distinct glutamate signaling mechanism underlying the peripheral processing of dental pain. This review discusses recent findings on the innervation of dental pulp and glutamate signaling by pulpal axons. First, recent findings on the morphological features and types of axons innervating the dental pulp are summarized. Then, glutamate signaling in the dental pulp and changes in the expression of VGLUT1 and VGLUT2 in the pulpal axons and TG neurons following pulpal inflammation are explained. Finally, findings on glutamate release from odontoblasts are briefly described.


Assuntos
Polpa Dentária , Odontoblastos , Animais , Dor , Ratos , Ratos Sprague-Dawley , Gânglio Trigeminal
5.
J Oral Sci ; 62(2): 131-135, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32132329

RESUMO

Nociceptive stimuli to the orofacial region are typically received by the peripheral terminal of trigeminal ganglion (TG) neurons, and noxious orofacial information is subsequently conveyed to the trigeminal spinal subnucleus caudalis and the upper cervical spinal cord (C1-C2). This information is further transmitted to the cortical somatosensory regions and limbic system via the thalamus, which then leads to the perception of pain. It is a well-established fact that the presence of abnormal pain in the orofacial region is etiologically associated with neuroplastic changes that may occur at any point in the pain transmission pathway from the peripheral to the central nervous system (CNS). Recently, several studies have reported that functional plastic changes in a large number of cells, including TG neurons, glial cells (satellite cells, microglia, and astrocytes), and immune cells (macrophages and neutrophils), contribute to the sensitization and disinhibition of neurons in the peripheral and CNS, which results in orofacial pain hypersensitivity.


Assuntos
Dor Facial , Gânglio Trigeminal , Animais , Microglia , Neuroglia , Ratos , Ratos Sprague-Dawley
6.
Am J Physiol Lung Cell Mol Physiol ; 318(5): L953-L964, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32159971

RESUMO

The lungs and the immune and nervous systems functionally interact to respond to respiratory environmental exposures and infections. The lungs are innervated by vagal sensory neurons of the jugular and nodose ganglia, fused together in smaller mammals as the jugular-nodose complex (JNC). Whereas the JNC shares properties with the other sensory ganglia, the trigeminal (TG) and dorsal root ganglia (DRG), these sensory structures express differential sets of genes that reflect their unique functionalities. Here, we used RNA sequencing (RNA-seq) in mice to identify the differential transcriptomes of the three sensory ganglia types. Using a fluorescent retrograde tracer and fluorescence-activated cell sorting, we isolated a defined population of airway-innervating JNC neurons and determined their differential transcriptional map after pulmonary exposure to lipopolysaccharide (LPS), a major mediator of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) after infection with gram-negative bacteria or inhalation of organic dust. JNC neurons activated an injury response program, leading to increased expression of gene products such as the G protein-coupled receptor Cckbr, inducing functional changes in neuronal sensitivity to peptides, and Gpr151, also rapidly induced upon neuropathic nerve injury in pain models. Unique JNC-specific transcripts, present at only minimal levels in TG, DRG, and other organs, were identified. These included TMC3, encoding for a putative mechanosensor, and urotensin 2B, a hypertensive peptide. These findings highlight the unique properties of the JNC and reveal that ALI/ARDS rapidly induces a nerve injury-related state, changing vagal excitability.


Assuntos
Gânglio Nodoso/efeitos dos fármacos , Pneumonia/genética , Receptor de Colecistocinina B/genética , Células Receptoras Sensoriais/efeitos dos fármacos , Transcriptoma , Traumatismos do Nervo Vago/genética , Animais , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/imunologia , Gânglios Espinais/patologia , Perfilação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Lipopolissacarídeos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Gânglio Nodoso/imunologia , Gânglio Nodoso/patologia , Hormônios Peptídicos/genética , Hormônios Peptídicos/imunologia , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pneumonia/patologia , Receptor de Colecistocinina B/imunologia , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/imunologia , Células Receptoras Sensoriais/imunologia , Células Receptoras Sensoriais/patologia , Análise de Sequência de RNA , Gânglio Trigeminal/efeitos dos fármacos , Gânglio Trigeminal/imunologia , Gânglio Trigeminal/patologia , Traumatismos do Nervo Vago/induzido quimicamente , Traumatismos do Nervo Vago/imunologia , Traumatismos do Nervo Vago/patologia
7.
Int Endod J ; 53(6): 846-858, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32058593

RESUMO

AIM: To determine whether Porphyromonas gingivalis lipopolysaccharide (LPS) can directly activate trigeminal neurons, to identify which receptors are involved and to establish whether activation leads to secretion of the neuropeptide calcitonin gene-related peptide (CGRP) and/or the translocation of NF-κB. METHODOLOGY: Mouse trigeminal ganglion (TG) cells were cultured in vitro for 2 days. The effect of P. gingivalis LPS (20 µg mL-1 ) on calcium signalling was assessed (by calcium imaging using Cal-520 AM) in comparison with the transient receptor potential channel A1 (TRPA1) agonist cinnamaldehyde (CA; 100 µmol L-1 ), the TRP channel V1 (TRPV1) agonist capsaicin (CAP; 1 µmol L-1 ) and high potassium (60 mmol L-1 KCl). TG cultures were pre-treated with either 1 µmol L-1 CLI-095 to block Toll-like receptor 4 (TLR4) signalling or with 3 µmol L-1 HC-030031 to block TRPA1 signalling. CGRP release was determined using ELISA, and nuclear translocation of NF-κB was investigated using immunocytochemistry. Data were analysed by one-way analysis of variance, followed by Bonferroni's post hoc test as appropriate. RESULTS: Porphyromonas gingivalis LPS directly exerted a rapid excitatory response on sensory neurons and non-neuronal cells (P < 0.001 to P < 0.05). The effects on neurons appear to be mediated via TLR4- and TRPA1-dependent pathways. The responses were accompanied by an increased release of CGRP (P < 0.001) and by NF-κB nuclear translocation (P < 0.01). CONCLUSIONS: Porphyromonas gingivalis LPS directly activated trigeminal sensory neurons (via TLR4 and TRPA1 receptors) and non-neuronal cells, resulting in CGRP release and NF-κB nuclear translocation. This indicates that P. gingivalis can directly influence activity in trigeminal sensory neurons and this may contribute to acute and chronic inflammatory pain.


Assuntos
Lipopolissacarídeos , Porphyromonas gingivalis , Animais , Camundongos , Dor , Células Receptoras Sensoriais , Gânglio Trigeminal
8.
J Oral Sci ; 62(1): 13-17, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31996516

RESUMO

Although xerostomia can cause persistent oral pain, the mechanisms underlying such pain are not well understood. To evaluate whether a phosphorylated p38 (pp38)-TRPV4 mechanism in trigeminal ganglion (TG) neurons has a role in mechanical hyperalgesia of dry tongue, a rat model of dry tongue was used to study the nocifensive reflex and pp38 and TRPV4 expression in TG neurons. The head-withdrawal reflex threshold for mechanical stimulation of the tongue was significantly lower in dry-tongue rats than in sham rats. The numbers of TRPV4- and pp38-immunoreactive cells in the TG were significantly higher in dry-tongue rats than in sham rats. Many TRPV4-IR cells were also pp38-immunoreactive. The number of TRPV1-IR cells was unchanged in the TG after induction of tongue dryness. Local injection of a TRPV4 blocker attenuated tongue mechanical hypersensitivity in dry-tongue rats. Intraganglionic injection of a selective p38 MAP kinase inhibitor eliminated tongue hypersensitivity in dry-tongue rats and suppressed TRPV4 expression in TG neurons. The present findings suggest that TRPV4 activation via p38 phosphorylation in TG neurons is involved in mechanical hypersensitivity associated with dry tongue. These mechanisms may have a role in pain associated with xerostomia.


Assuntos
Canais de Cátion TRPV , Gânglio Trigeminal , Animais , Hiperalgesia , Ratos , Ratos Sprague-Dawley , Língua
9.
Toxicol Lett ; 319: 74-84, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31707104

RESUMO

Benzalkonium chloride (BAK), a quaternary ammonium compound widely used as disinfecting agent as well as preservative in eye drops is known to induce toxic effects on the ocular surface with inflammation and corneal nerve damage leading to dry eye disease (DED) in the medium-to-long term. The aim of this study was to evaluate in vitro the toxicity of a conditioned medium produced by corneal epithelial cells previously exposed to BAK (BAK-CM) on trigeminal neuronal cells. A human corneal epithelial (HCE) cell line was exposed to 5.10-3% BAK (i.e. 0.005% BAK) for 15 min and let recover for 5 h to prepare a BAK-CM. This BAK concentration is the lowest one found in eye drops. After this recovery period, BAK effect on HCE cells displayed cytotoxicity, morphological alteration, apoptosis, oxidative stress, ATP release, CCL2 and IL6 gene induction, as well as an increase in CCL2, IL-6 and MIF release. Next, a mouse trigeminal ganglion primary culture was exposed to the BAK-CM for 2 h, 4 h or 24 h. Whereas BAK-CM did not alter neuronal cell morphology, or induced neuronal cytotoxicity or oxidative stress, BAK-CM induced gene expression of Fos (neuronal activation marker), Atf3 (neuronal injury marker), Ccl2 and Il6 (inflammatory markers). Two and 4 h BAK-CM exposure promoted a neuronal damage (ATF-3, phospho-p38 increases; phospho-Stat3 decreases) while 24 h-BAK-CM exposure initiated a prosurvival pathway activation (phospho-p44/42, phospho-Akt increases; ATF-3, GADD153, active Caspase-3 decreases). In conclusion, this in vitro model, simulating paracrine mechanisms, represents an interesting tool to highlight the indirect toxic effects of BAK or any other xenobiotic on corneal trigeminal neurons and may help to better understand the cellular mechanisms that occur during DED pathophysiology.


Assuntos
Apoptose/efeitos dos fármacos , Compostos de Benzalcônio/toxicidade , Células Epiteliais/efeitos dos fármacos , Epitélio Anterior/efeitos dos fármacos , Inflamação/induzido quimicamente , Neurônios/efeitos dos fármacos , Conservantes Farmacêuticos/toxicidade , Gânglio Trigeminal/efeitos dos fármacos , Fator 3 Ativador da Transcrição/biossíntese , Fator 3 Ativador da Transcrição/efeitos dos fármacos , Animais , Linhagem Celular , Síndromes do Olho Seco/induzido quimicamente , Síndromes do Olho Seco/patologia , Epitélio Anterior/citologia , Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Gânglio Trigeminal/citologia
10.
World Neurosurg ; 134: e214-e223, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31627002

RESUMO

INTRODUCTION: Persistent trigeminal artery (PTA) is the most common remnant of primitive circulation communicating the developing carotid and vertebrobasilar junction. Although discovered incidentally, an altered hemodynamic may lead to an increased association of aneurysms, vascular malformations, and stroke. Neurosurgeons should be aware of the presence and significance of PTA when interpreting imaging and planning interventions. METHODS: We retrospectively reviewed all magnetic resonance angiography and cerebral digital subtraction angiography performed between 2012 and 2017 for the presence of PTA. The radiologic and anatomic details were noted and analyzed along with the clinical profiles. We categorized the radiologic findings with respect to the available classification systems. A review of the available literature was done comparing our results. RESULTS: We found 33 cases of incidentally detected PTA. The average age of the patients was 45.42 years. The lateral surface of the proximal cavernous internal carotid artery was the most common origin (n = 23). Only 3 cases had a medial/transsellar course. Most cases were Saltzman/Weon type I (19/33). Intracranial aneurysms were associated with 6 patients (18.18%). Trigeminal neuralgia (TN) was a presenting feature in 5 patients. None had a direct neurovascular conflict at the root entry zone. CONCLUSIONS: Our study is one of the largest to describe the incidence of PTA. We emphasized the importance of PTA to the neurosurgeons; increased association of aneurysms, as a route for intervention in occlusive disease of the posterior fossa; risk of injury and bleeding during transsphenoidal surgery; and the association with TN. However, we found that only PTA variants are likely to be associated with TN because of their cisternal course causing NV conflict.


Assuntos
Malformações Arteriovenosas/diagnóstico por imagem , Artérias Cerebrais/anormalidades , Artérias Cerebrais/diagnóstico por imagem , Aneurisma Intracraniano/diagnóstico por imagem , Neuralgia do Trigêmeo/diagnóstico por imagem , Adolescente , Adulto , Idoso , Angiografia Digital/métodos , Malformações Arteriovenosas/cirurgia , Artérias Cerebrais/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Aneurisma Intracraniano/cirurgia , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Gânglio Trigeminal/irrigação sanguínea , Gânglio Trigeminal/diagnóstico por imagem , Gânglio Trigeminal/cirurgia , Neuralgia do Trigêmeo/cirurgia , Adulto Jovem
11.
J Oral Pathol Med ; 49(2): 169-176, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31829463

RESUMO

BACKGROUND: Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine that plays an important role in the early stages of inflammation. In this study, we investigated its role in orofacial discomfort in rats subjected to occlusal dental interference (ODI). METHODS: Female Wistar rats (180-200 g) were divided in three groups (n = 30/group): sham group, without ODI, and two experimental groups with ODI pre-treated with 0.1 mL/kg saline (ODI + SAL) or 5 mg/kg infliximab (ODI + INF) and treated every 3 days. The animals were euthanized after 1, 3, and 7 days. The number of bites and scratches and grimace scale scores were determined daily, and the bilateral trigeminal ganglion was histomorphometrically (neuronal body area) analyzed and submitted for immunohistochemistry for TNF-α, nitric oxide synthesis (NOS) neuronal (nNOS) and inducible (iNOS), peroxisome proliferator-activated receptors (PPAR) y (PPARy) and δ/ß (PPARδ/ß), and glial fibrillary acidic protein (GFAP). One-way/two-way ANOVA/Bonferroni tests were used (P < .05, GraphPad Prism 5.0). RESULTS: ODI + SAL showed a large number of bites (P = .002), scratches (P = .002), and grimace scores (P < .001) in the firsts days, and ODI + INF partially reduced these parameters. The contralateral and ipsilateral neuronal body area was significantly reduced on day 1 in ODI + SAL, but returned to the basal size on days 3 and 7, by increase in TNF-α, nNOS, PPARy, PPARδ/ß, and GFAP immunostaining. The infliximab treatment attenuated these alterations (P < .05). There was no iNOS immunostaining. CONCLUSION: Occlusal dental interference induced transitory orofacial discomfort by trigeminal inflammatory mediator overexpression, and TNF-α blockage attenuated these processes.


Assuntos
Gânglio Trigeminal , Animais , Citocinas , Feminino , Inflamação , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa
12.
Int Endod J ; 53(1): 62-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31411737

RESUMO

AIM: To verify whether experimentally induced pulpitis activates the expression of transient receptor potential vanilloid type 1 (TRPV1) and c-Fos, both peripherally and centrally. METHODOLOGY: Acute pulpitis was induced in Sprague-Dawley rats via pulp exposure and application of complete Freund's adjuvant (CFA; n = 13). Saline-treated (n = 13) rats and rats that did not undergo tooth preparation (n = 13) served as control groups. Three days post-CFA or post-saline application, face grooming activity was recorded, and the rats were then euthanized to allow for immunohistochemical analysis of the trigeminal ganglion (TG) and spinal trigeminal nucleus. anova with Student's t-test for post-hoc analysis was used to quantify the differences in behavioural tests and immunohistochemical labelling (c-Fos and TRPV1) in TG amongst groups. Kruskal-Wallis test with Dunnett's test for post-hoc analysis was used to compare immunohistochemical labelling (c-Fos and TRPV1) in the brainstem amongst groups. RESULTS: Histological evidence of severe pulp inflammation was found, and there was a significant increase in pain-like behaviour (P < 0.05) in CFA-treated animals. C-Fos labelling and TRPV1 immunoreactivity in the TG were significantly higher (both P < 0.05) in the CFA group than in the control groups. In the spinal trigeminal nucleus, the immunoreactivity for c-Fos was absent in the intermediate region (trigeminal subnucleus interpolaris) in all animals, with comparable expression of TRPV1 amongst all groups. In contrast, neurons in the trigeminal subnucleus caudalis (TSC) exhibited significant c-Fos immunoreactivity in the CFA group (P = 0.0063). The expression of TRPV1 did not differ amongst the three groups, but the superficial laminae of the TSC exhibited significantly greater expression of TRPV1 than did the deep layers (P = 0.0014). CONCLUSIONS: Following acute pulp inflammation, the TRPV1 channel was significantly involved in nociceptive signal processing in the peripheral nervous system, but not in the CNS. Because pulpitis induced some neuronal activation at the brainstem levels, further studies are needed to identify additional transducers that mediate signal transmission from pulpal afferents to their central targets.


Assuntos
Polpa Dentária , Gânglio Trigeminal , Animais , Tronco Encefálico , Inflamação , Proteínas Proto-Oncogênicas c-fos , Ratos , Ratos Sprague-Dawley , Papel (figurativo)
13.
Invest Ophthalmol Vis Sci ; 60(15): 4972-4984, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790560

RESUMO

Purpose: The subbasal nerve plexus (SNP) is the densest and most recognizable component of the mammalian corneal innervation; however, the anatomical configuration of the SNP in most animal models remains incompletely described. The purpose of the current study is to describe in detail the SNP architecture in eight different mammals, including several popular animal models used in cornea research. Methods: Corneal nerves in mouse, rat, guinea pig, rabbit, dog, macaque, domestic pig, and cow eyes were stained immunohistochemically with antiserum directed against neurotubulin. SNP architecture was documented by digital photomicrography and large-scale reconstructions, that is, corneal nerve maps, using a drawing tube attached to a light microscope. Results: Subbasal nerve fibers (SNFs) in mice, rats, guinea pigs, dogs, and macaques radiated centrally from the corneoscleral limbus toward the corneal apex in a whorl-like or spiraling pattern. SNFs in rabbit and bovine corneas swept horizontally across the ocular surface in a temporal-to-nasal direction and converged on the inferonasal limbus without forming a spiral. SNFs in the pig cornea radiated centrifugally in all directions, like a starburst, from a focal point located equidistant between the corneal apex and the superior pole. Conclusions: The results of the present study have demonstrated for the first time substantial interspecies differences in the architectural organization of the mammalian SNP. The physiological significance of these different patterns and the mechanisms that regulate SNP pattern formation in the mammalian cornea remain incompletely understood and warrant additional investigation.


Assuntos
Anatomia Comparada , Córnea/inervação , Nervo Oftálmico/anatomia & histologia , Animais , Bovinos , Cães , Cobaias , Macaca , Camundongos , Microscopia Confocal , Modelos Animais , Fibras Nervosas , Coelhos , Ratos , Suínos , Gânglio Trigeminal/anatomia & histologia
14.
Artigo em Russo | MEDLINE | ID: mdl-31793545

RESUMO

The article presents in detail the history of the discovery of the trigeminal ganglion in the context to name it Gasserian ganglion. The historical, formal and logical methods of research, along with system analysis were used in the work. An in-depth research of little-known literature sources, which included scientific, publicistic and fiction components, was conducted. The authors for the first time translated into Russian the IV Chapter of Antonius Hirsch's dissertation 'Paris quinti nervorum encephali disquisition anatomica'. This researcher presented the anatomical views of the leading scientists of the time, and their own data on the mechanical properties, features of the topography and preparation of the trigeminal ganglion. The analysis of the literature allowed clearly following the chronology of the discovery of Gasserian ganglion, highlighting the most significant facts of the biography of scientists and recreating the history of anatomy in this area.


Assuntos
Gânglio Trigeminal , Neuralgia do Trigêmeo , Humanos , Federação Russa
15.
Int J Mol Sci ; 20(24)2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31861182

RESUMO

Insulin-like growth factor-1 (IGF-1) is upregulated in the injured peripheral nerve bundle and controls nociceptive neuronal excitability associated with peripheral nerve injury. Here, we examined the involvement of IGF-1 signaling in orofacial neuropathic pain following infraorbital nerve injury (IONI) in rats. IONI promoted macrophage accumulation in the injured ION, as well as in the ipsilateral trigeminal ganglion (TG), and induced mechanical allodynia of the whisker pad skin together with the enhancement of neuronal activities in the subnucleus caudalis of the spinal trigeminal nucleus and in the upper cervical spinal cord. The levels of IGF-1 released by infiltrating macrophages into the injured ION and the TG were significantly increased. The IONI-induced the number of transient receptor potential vanilloid (TRPV) subfamily type 4 (TRPV4) upregulation in TRPV subfamily type 2 (TRPV2)-positive small-sized, and medium-sized TG neurons were inhibited by peripheral TRPV2 antagonism. Furthermore, the IONI-induced mechanical allodynia was suppressed by TRPV4 antagonism in the whisker pad skin. These results suggest that IGF-1 released by macrophages accumulating in the injured ION binds to TRPV2, which increases TRPV4 expression in TG neurons innervating the whisker pad skin, ultimately resulting in mechanical allodynia of the whisker pad skin.


Assuntos
Dor Facial/metabolismo , Hiperalgesia/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Neuralgia/metabolismo , Traumatismos do Nervo Trigêmeo/metabolismo , Animais , Dor Facial/fisiopatologia , Hiperalgesia/fisiopatologia , Macrófagos/metabolismo , Masculino , Neuralgia/fisiopatologia , Neurônios/metabolismo , Limiar da Dor , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Canais de Cátion TRPV/metabolismo , Gânglio Trigeminal , Traumatismos do Nervo Trigêmeo/fisiopatologia , Vibrissas/inervação , Vibrissas/metabolismo
16.
J Neuroinflammation ; 16(1): 268, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847868

RESUMO

BACKGROUND: Dry eye disease (DED) is a multifactorial disease associated with ocular surface inflammation, pain, and nerve abnormalities. We studied the peripheral and central neuroinflammatory responses that occur during persistent DED using molecular, cellular, behavioral, and electrophysiological approaches. METHODS: A mouse model of DED was obtained by unilateral excision of the extraorbital lachrymal gland (ELG) and Harderian gland (HG) of adult female C57BL/6 mice. In vivo tests were conducted at 7, 14, and 21 days (d) after surgery. Tear production was measured by a phenol red test and corneal alterations and inflammation were assessed by fluorescein staining and in vivo confocal microscopy. Corneal nerve morphology was evaluated by nerve staining. Mechanical corneal sensitivity was monitored using von Frey filaments. Multi-unit extracellular recording of ciliary nerve fiber activity was used to monitor spontaneous corneal nerve activity. RT-qPCR and immunostaining were used to determine RNA and protein levels at d21. RESULTS: We observed a marked reduction of tear production and the development of corneal inflammation at d7, d14, and d21 post-surgery in DED animals. Chronic DE induced a reduction of intraepithelial corneal nerve terminals. Behavioral and electrophysiological studies showed that the DED animals developed time-dependent mechanical corneal hypersensitivity accompanied by increased spontaneous ciliary nerve fiber electrical activity. Consistent with these findings, DED mice exhibited central presynaptic plasticity, demonstrated by a higher Piccolo immunoreactivity in the ipsilateral trigeminal brainstem sensory complex (TBSC). At d21 post-surgery, mRNA levels of pro-inflammatory (IL-6 and IL-1ß), astrocyte (GFAP), and oxidative (iNOS2 and NOX4) markers increased significantly in the ipsilateral trigeminal ganglion (TG). This correlated with an increase in Iba1, GFAP, and ATF3 immunostaining in the ipsilateral TG of DED animals. Furthermore, pro-inflammatory cytokines (IL-6, TNFα, IL-1ß, and CCL2), iNOS2, neuronal (ATF3 and FOS), and microglial (CD68 and Itgam) markers were also upregulated in the TBSC of DED animals at d21, along with increased immunoreactivity against GFAP and Iba1. CONCLUSIONS: Overall, these data highlight peripheral sensitization and neuroinflammatory responses that participate in the development and maintenance of dry eye-related pain. This model may be useful to identify new analgesic molecules to alleviate ocular pain.


Assuntos
Córnea/fisiopatologia , Síndromes do Olho Seco/fisiopatologia , Hiperalgesia/fisiopatologia , Plasticidade Neuronal/fisiologia , Núcleos do Trigêmeo/fisiopatologia , Animais , Doença Crônica , Feminino , Inflamação/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Gânglio Trigeminal/fisiopatologia
17.
Oral Dis ; 25(8): 1850-1865, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31733122

RESUMO

The natural history of oral herpes simplex virus type 1 (HSV-1) infection in the immunocompetent host is complex and rich in controversial phenomena, namely the role of unapparent transmission in primary infection acquisition, the high frequency of asymptomatic primary and recurrent infections, the lack of immunogenicity of HSV-1 internalized in the soma (cell body) of the sensory neurons of the trigeminal ganglion, the lytic activity of HSV-1 in the soma of neurons that is inhibited in the sensory neurons of the trigeminal ganglion and often uncontrolled in the other neurons, the role of keratin in promoting the development of recurrence episodes in immunocompetent hosts, the virus-host Nash equilibrium, the paradoxical HSV-1-seronegative individuals who shed HSV-1 through saliva, the limited efficacy of anti-HSV vaccines, and why the oral route of infection is the least likely to produce severe complications. The natural history of oral HSV-1 infection is also a history of symbiosis between humans and virus that may switch from mutualism to parasitism and vice versa. This balance is typical of microorganisms that are highly coevolved with humans, and its knowledge is essential to oral healthcare providers to perform adequate diagnosis and provide proper individual-based HSV-1 infection therapy.


Assuntos
Herpes Labial , Herpes Simples , Herpesvirus Humano 1 , Estomatite Herpética , Humanos , Gânglio Trigeminal
18.
J Headache Pain ; 20(1): 105, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718551

RESUMO

BACKGROUND: Monoclonal antibodies (mAbs) towards CGRP or the CGRP receptor show good prophylactic antimigraine efficacy. However, their site of action is still elusive. Due to lack of passage of mAbs across the blood-brain barrier the trigeminal system has been suggested a possible site of action because it lacks blood-brain barrier and hence is available to circulating molecules. The trigeminal ganglion (TG) harbors two types of neurons; half of which store CGRP and the rest that express CGRP receptor elements (CLR/RAMP1). METHODS: With specific immunohistochemistry methods, we demonstrated the localization of CGRP, CLR, RAMP1, and their locations related to expression of the paranodal marker contactin-associated protein 1 (CASPR). Furthermore, we studied functional CGRP release separately from the neuron soma and the part with only nerve fibers of the trigeminal ganglion, using an enzyme-linked immunosorbent assay. RESULTS: Antibodies towards CGRP and CLR/RAMP1 bind to two different populations of neurons in the TG and are found in the C- and the myelinated Aδ-fibers, respectively, within the dura mater and in trigeminal ganglion (TG). CASPR staining revealed paranodal areas of the different myelinated fibers inhabiting the TG and dura mater. Double immunostaining with CASPR and RAMP1 or the functional CGRP receptor antibody (AA58) revealed co-localization of the two peptides in the paranodal region which suggests the presence of the CGRP-receptor. Double immunostaining with CGRP and CASPR revealed that thin C-fibers have CGRP-positive boutons which often localize in close proximity to the nodal areas of the CGRP-receptor positive Aδ-fibers. These boutons are pearl-like synaptic structures, and we show CGRP release from fibers dissociated from their neuronal bodies. In addition, we found that adjacent to the CGRP receptor localization in the node of Ranvier there was PKA immunoreactivity (kinase stimulated by cAMP), providing structural possibility to modify conduction activity within the Aδ-fibers. CONCLUSION: We observed a close relationship between the CGRP containing C-fibers and the Aδ-fibers containing the CGRP-receptor elements, suggesting a point of axon-axon interaction for the released CGRP and a site of action for gepants and the novel mAbs to alleviate migraine.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Nós Neurofibrosos/metabolismo , Proteína 1 Modificadora da Atividade de Receptores/metabolismo , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismo , Gânglio Trigeminal/metabolismo , Animais , Axônios , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/metabolismo , Dura-Máter/metabolismo , Imuno-Histoquímica , Masculino , Transtornos de Enxaqueca/fisiopatologia , Fibras Nervosas/metabolismo , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
19.
Beijing Da Xue Xue Bao Yi Xue Ban ; 51(5): 973-976, 2019 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-31624409

RESUMO

OBJECTIVE: To evaluate the accuracy and feasibility of a custom robot system guided by optical navigation for needle puncture on trigeminal gasserian ganglion. METHODS: A synthetic human skull model was used, with plasticine placed around the skull base to imitate the human soft tissue. Cone beam CT (CBCT) scanning was performed before the operation. With image data transferred to the graphical user interface of the computer workstation, the oval foramen was selected as the target and the "skin entry point" was also determined by the surgeon on the surgical planning software. Thus the needle trajectory was eventually planned. The skull model was fixed firmly to the trial table with a head clamp and relative size of the trial table was the same as a standard operating table. Following point-based registration, the data were sent to the robot control unit. Only after the surgeon's confirmation, the needle was automatically inserted into the intended target by the robot guided by optical navigation. When the procedure was completed, the instantaneous data of the needle tip orientation acquired by navigation system was sent back to the computer workstation for accuracy verification by calculating the geometric distance between the needle tip and the planning target after matrix transformation. Subsequently, after the needle had been released, CBCT scanning was also acquired to make image fusion of the preoperative skull and the postoperative skull. The data of the needle tip orientation was acquired on the postoperative image and the accuracy was re-verified by calculating the geometric distance between the needle tip and the planning target after matrix transformation. IBM SPSS Statistics 20 was used for statistical analysis and the paired t-test was used to compare the differences in the accuracy measured by the intraoperative navigation and postoperative image fusion. RESULTS: All 20 interventions were successfully located in oval foramen at the first needle insertion. The mean deviation of the needle tip was (0.56±0.07) mm (measured by the navigation system) and (1.49±0.14) mm (measured by the image fusion), respectively (P<0.001). CONCLUSION: The experimental results show the robot system is efficient and reliable. The navigation accuracy is one of the most significant factors in robotic procedures.


Assuntos
Procedimentos Cirúrgicos Robóticos , Humanos , Agulhas , Robótica , Cirurgia Assistida por Computador , Gânglio Trigeminal
20.
Sheng Li Xue Bao ; 71(5): 741-748, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31646328

RESUMO

Rodent MrgC receptor (Mas-related G-protein-coupled receptor subtype C) shares 65% sequence homology and similarities in terms of expression pattern and binding profile with human Mas-related gene X receptor 1 (hMrgX1). Therefore, researchers generally explore the role of hMrgX1 by studying the function of MrgC receptor. Murine MrgC receptor is uniquely expressed in small-diameter neurons of dorsal root ganglia (DRG) and trigeminal ganglia (TG), which is closely related to the transmission process of pain. This review summarizes the analgesic effects of intrathecal activation of MrgC receptors in pathological pain and morphine tolerance.


Assuntos
Tolerância a Medicamentos , Morfina/farmacologia , Dor , Receptores Acoplados a Proteínas-G/fisiologia , Animais , Gânglios Espinais , Humanos , Camundongos , Fragmentos de Peptídeos , Ratos , Ratos Sprague-Dawley , Gânglio Trigeminal
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