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1.
Invest Ophthalmol Vis Sci ; 63(1): 7, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34989761

RESUMO

Purpose: Dry eye-induced chronic ocular pain is also called ocular neuropathic pain. However, details of the pathogenic mechanism remain unknown. The purpose of this study was to elucidate the pathogenic mechanism of dry eye-induced chronic pain in the anterior eye area and develop a pathophysiology-based therapeutic strategy. Methods: We used a rat dry eye model with lacrimal gland excision (LGE) to elucidate the pathogenic mechanism of ocular neuropathic pain. Corneal epithelial damage, hypersensitivity, and hyperalgesia were evaluated on the LGE side and compared with the sham surgery side. We analyzed neuronal activity, microglial and astrocytic activity, α2δ-1 subunit expression, and inhibitory interneurons in the trigeminal nucleus. We also evaluated the therapeutic effects of ophthalmic treatment and chronic pregabalin administration on dry eye-induced ocular neuropathic pain. Results: Dry eye caused hypersensitivity and hyperalgesia on the LGE side. In the trigeminal nucleus of the LGE side, neuronal hyperactivation, transient activation of microglia, persistent activation of astrocytes, α2δ-1 subunit upregulation, and reduced numbers of inhibitory interneurons were observed. Ophthalmic treatment alone did not improve hyperalgesia. In contrast, continuous treatment with pregabalin effectively ameliorated hypersensitivity and hyperalgesia and normalized neural activity, α2δ-1 subunit upregulation, and astrocyte activation. Conclusions: These results suggest that dry eye-induced hypersensitivity and hyperalgesia are caused by central sensitization in the trigeminal nucleus with upregulation of the α2δ-1 subunit. Here, we showed that pregabalin is effective for treating dry eye-induced ocular neuropathic pain even after chronic pain has been established.


Assuntos
Analgésicos/administração & dosagem , Modelos Animais de Doenças , Síndromes do Olho Seco/fisiopatologia , Dor Ocular/fisiopatologia , Pregabalina/administração & dosagem , Administração Oftálmica , Animais , Astrócitos/patologia , Canais de Cálcio Tipo L/metabolismo , Doença Crônica , Córnea/inervação , Síndromes do Olho Seco/tratamento farmacológico , Dor Ocular/tratamento farmacológico , Ácido Hialurônico/administração & dosagem , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Masculino , Microglia/patologia , Neuralgia/tratamento farmacológico , Neuralgia/fisiopatologia , Neurônios/metabolismo , Neurônios/patologia , Soluções Oftálmicas , Ratos , Ratos Sprague-Dawley , Nervo Trigêmeo/metabolismo , Nervo Trigêmeo/patologia
2.
Biochim Biophys Acta Mol Cell Res ; 1869(1): 119146, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599984

RESUMO

Gaba-ergic neurons are a diverse cell class with extensive influence over cortical processing, but their role in experience-dependent plasticity is not completely understood. Here we addressed the role of cortical somatostatin- (SOM-INs) and vasoactive intestinal polypeptide- (VIP-INs) containing interneurons in a Pavlovian conditioning where stimulation of the vibrissae is used as a conditioned stimulus and tail shock as unconditioned one. This procedure induces a plastic change observed as an enlargement of the cortical functional representation of vibrissae activated during conditioning. Using layer-targeted, cell-selective DREADD transductions, we examined the involvement of SOM-INs and VIP-INs activity in learning-related plastic changes. Under optical recordings, we injected DREADD-expressing vectors into layer IV (L4) barrels or layer II/III (L2/3) areas corresponding to the activated vibrissae. The activity of the interneurons was modulated during all conditioning sessions, and functional 2-deoxyglucose (2DG) maps were obtained 24 h after the last session. In mice with L4 but not L2/3 SOM-INs suppressed during conditioning, the plastic change of whisker representation was absent. The behavioral effect of conditioning was disturbed. Both L4 SOM-INs excitation and L2/3 VIP-INs inhibition during conditioning did not affect the plasticity or the conditioned response. We found the activity of L4 SOM-INs is indispensable in the formation of learning-induced plastic change. We propose that L4 SOM-INs may provide disinhibition by blocking L4 parvalbumin interneurons, allowing a flow of information into upper cortical layers during learning.


Assuntos
Interneurônios/fisiologia , Aprendizagem , Inibição Neural , Plasticidade Neuronal , Córtex Somatossensorial/fisiologia , Animais , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/fisiologia , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Moduladores de Transporte de Membrana/farmacologia , Camundongos , Córtex Somatossensorial/citologia , Somatostatina/genética , Somatostatina/metabolismo , Vibrissas/inervação , Vibrissas/fisiologia
3.
Cell Mol Life Sci ; 79(1): 7, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34936028

RESUMO

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons and severe muscle atrophy without effective treatment. Most research on the disease has been focused on studying motor neurons and supporting cells of the central nervous system. Strikingly, the recent observations have suggested that morpho-functional alterations in skeletal muscle precede motor neuron degeneration, bolstering the interest in studying muscle tissue as a potential target for the delivery of therapies. We previously showed that the systemic administration of the P2XR7 agonist, 2'(3')-O-(4-benzoylbenzoyl) adenosine 5-triphosphate (BzATP), enhanced the metabolism and promoted the myogenesis of new fibres in the skeletal muscles of SOD1G93A mice. Here we further corroborated this evidence showing that intramuscular administration of BzATP improved the motor performance of ALS mice by enhancing satellite cells and the muscle pro-regenerative activity of infiltrating macrophages. The preservation of the skeletal muscle retrogradely propagated along with the motor unit, suggesting that backward signalling from the muscle could impinge on motor neuron death. In addition to providing the basis for a suitable adjunct multisystem therapeutic approach in ALS, these data point out that the muscle should be at the centre of ALS research as a target tissue to address novel therapies in combination with those oriented to the CNS.


Assuntos
Esclerose Amiotrófica Lateral/metabolismo , Esclerose Amiotrófica Lateral/fisiopatologia , Atividade Motora/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Receptores Purinérgicos P2X7/metabolismo , Trifosfato de Adenosina/administração & dosagem , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Animais , Axônios/patologia , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Denervação , Modelos Animais de Doenças , Progressão da Doença , Feminino , Membro Posterior/patologia , Humanos , Inflamação/patologia , Injeções Intramusculares , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Transgênicos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/inervação , Atrofia Muscular/patologia , Fenótipo , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Células Satélites de Músculo Esquelético/patologia , Células de Schwann/patologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia
4.
Isr Med Assoc J ; 23(12): 773-776, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34954915

RESUMO

BACKGROUND: The current approach to performing sacral neuromodulation consists of a two-stage procedure, the first of which includes insertion of the sacral electrode under fluoroscopic visualization of the S3 foramen. Alternatively, in certain situations computed tomography (CT)-guided insertion can be used. OBJECTIVES: To evaluate the use of CT in cases of reinsertion of the electrode due to infection, dislocation, or rupture. METHODS: Medical records of patients who underwent neuromodulation device reinsertion between 2005 and 2016 for fecal incontinence were reviewed. Study outcomes included procedure course, successful placement, and long-term treatment success. RESULTS: During the study period, we inserted a neuromodulation device in 67 patients. A CT-guided insertion of a sacral electrode was performed in 10 patients. In nine patients, the insertion and the final location of the electrode were successful. In one patient, the electrode migrated upward due to a malformation of the S3 foramen on both sides and had to be placed in S4. In a mean follow-up of 68.4 ± 30.0 months following the re-insertion, there was a significant reduction in the number of incontinence episodes per day (P < 0.001) and the number of pads used per day (P = 0.002). CONCLUSIONS: CT-guided insertion of a sacral electrode is a safe and promising option, especially in recurrent and or selected cases.


Assuntos
Terapia por Estimulação Elétrica/métodos , Incontinência Fecal/terapia , Sacro/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Idoso , Eletrodos Implantados , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Sacro/inervação
5.
Medicine (Baltimore) ; 100(41): e27536, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731150

RESUMO

ABSTRACT: Carpal tunnel syndrome (CTS) is a common neuropathy. Although CTS progression is known to be associated with thenar muscle (TM) atrophy, the diagnostic value of TM atrophy for CTS has not been established. In this research, the thenar muscle cross-sectional area (TMCSA) was evaluated to analyze the relationship between the TMCSA and CTS. We assumed that TMCSA is a major diagnostic parameter in the CTS.Both TMCSA and thenar muscle thickness (TMT) samples were acquired from 18 CTS patients, and from 18 control subjects who underwent wrist magnetic resonance imaging with no evidence of CTS. T2-weighted transverse magnetic resonance imaging images were obtained. We measured the TMCSA and TMT at the level of first carpometacarpal joint.The average TMCSA was 296.98 ±â€Š49.39 mm2 in the normal group and 203.36 ±â€Š72.13 mm2 in the CTS group. The average TMT was 8.54 ±â€Š1.45 mm in the normal group and 7.38 ±â€Š1.14 mm in the CTS group. CTS group had significantly lower TMCSA and TMT. Receiver operator characteristics curve analysis showed that the best cutoff point for the TMCSA was 260.18 mm2, with 77.8% sensitivity, 77.8% specificity. The best cutoff point of the TMT was 7.70 mm, with 61.1% sensitivity, 66.7% specificity.Although the TMCSA and TMT were both significantly associated with CTS, the TMCSA was a much more sensitive measurement parameter. Thus, to evaluate CTS patients, the physician should more carefully inspect the TMCSA than TMT.


Assuntos
Anatomia Transversal/instrumentação , Síndrome do Túnel Carpal/diagnóstico , Imageamento por Ressonância Magnética/métodos , Nervo Mediano/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Adulto , Atrofia/diagnóstico , Atrofia/etiologia , Síndrome do Túnel Carpal/patologia , Estudos de Casos e Controles , Feminino , Mãos/anatomia & histologia , Mãos/inervação , Humanos , Masculino , Nervo Mediano/patologia , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Articulação do Punho/diagnóstico por imagem
6.
Nat Commun ; 12(1): 5812, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608164

RESUMO

The advantage of locally applied anesthetics is that they are not associated with the many adverse effects, including addiction liability, of systemically administered analgesics. This therapeutic approach has two inherent pitfalls: specificity and a short duration of action. Here, we identified nociceptor endocytosis as a promising target for local, specific, and long-lasting treatment of inflammatory pain. We observed preferential expression of AP2α2, an α-subunit isoform of the AP2 complex, within CGRP+/IB4- nociceptors in rodents and in CGRP+ dorsal root ganglion neurons from a human donor. We utilized genetic and pharmacological approaches to inhibit nociceptor endocytosis demonstrating its role in the development and maintenance of acute and chronic inflammatory pain. One-time injection of an AP2 inhibitor peptide significantly reduced acute and chronic pain-like behaviors and provided prolonged analgesia. We evidenced sexually dimorphic recovery responses to this pharmacological approach highlighting the importance of sex differences in pain development and response to analgesics.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Dor Crônica/tratamento farmacológico , Endocitose/efeitos dos fármacos , Nociceptores/efeitos dos fármacos , Complexo 2 de Proteínas Adaptadoras/antagonistas & inibidores , Complexo 2 de Proteínas Adaptadoras/genética , Complexo 2 de Proteínas Adaptadoras/metabolismo , Subunidades alfa do Complexo de Proteínas Adaptadoras/antagonistas & inibidores , Subunidades alfa do Complexo de Proteínas Adaptadoras/genética , Subunidades alfa do Complexo de Proteínas Adaptadoras/metabolismo , Animais , Dor Crônica/metabolismo , Dor Crônica/fisiopatologia , Epiderme/inervação , Feminino , Gânglios Espinais/metabolismo , Humanos , Inflamação , Masculino , Camundongos , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/metabolismo , Nociceptores/metabolismo , Nociceptores/fisiologia , Peptídeos/administração & dosagem , Peptídeos/metabolismo , Peptídeos/farmacologia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia
7.
Medicine (Baltimore) ; 100(39): e27285, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596124

RESUMO

RATIONALE: Ramsay Hunt syndrome is a type of herpes zoster infection involving geniculate ganglion and facial nerve. Unilateral facial palsy, otalgia, and painful vesicular rash on the auricle and external auditory canal are the typical symptoms. Although postherpetic neuralgia (PHN) is a devastating complication of herpes zoster infection, PHN following Ramsay Hunt syndrome has rarely been reported. PATIENT CONCERNS: A 55-year-old immunocompetent female patient visited our pain clinic, for left-sided refractory otalgia (PHN) that persisted for 3 months after she was diagnosed with Ramsay Hunt syndrome. Although facial palsy and tinnitus had recovered within 2 to 4 weeks after symptom onset, the patient had been experiencing a persistent and severe otalgia radiating to mandibular angle, temporal and upper cervical area of neuropathic nature. DIAGNOSES: The patient's pain persisted despite conservative medication and administration of ultrasound-guided stellate ganglion block, facial nerve block, and great auricular nerve block several times. INTERVENTIONS: The patient was treated with the application of ultrasound-guided pulsed radiofrequency (PRF) to the great auricular nerve. OUTCOMES: The patient experienced significant pain reduction more than 50% on a numeric rating scale after 2 weeks of PRF treatment. LESSONS: Chronic otalgia might be a type of PHN after Ramsay Hunt syndrome with cervical nerve involvement. PRF treatment to the great auricular nerve can be a therapeutic option for refractory otalgia following Ramsay Hunt syndrome.


Assuntos
Dor de Orelha/terapia , Herpes Zoster da Orelha Externa/terapia , Tratamento por Radiofrequência Pulsada , Orelha/inervação , Dor de Orelha/etiologia , Feminino , Herpes Zoster da Orelha Externa/complicações , Humanos , Pessoa de Meia-Idade , Indução de Remissão
8.
Medicine (Baltimore) ; 100(43): e27621, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34713849

RESUMO

RATIONALE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with the fatal course of muscle weakness. The published experience of anesthesia management in the cesarean section with ALS parturient is scant. PATIENT CONCERNS: A 34-year-old woman was admitted to our center complaining of obvious dysphagia together with atrophy and weakness of quadriceps at 24 weeks of her pregnancy. Cesarean was planned at 36 weeks' gestation due to the rapid deterioration of the mother. DIAGNOSES: The results of neurological examination, electromyography and spinal magnetic resonance imaging suggested ALS according to the EI Escorial World Federation of Neurology criteria. INTERVENTIONS: Ultrasound-guided transversus abdominis plane block with 0.6 minimum alveolar concentration sevoflurane was used in this ALS parturient during her cesarean section procedure. OUTCOMES: This anesthesia strategy successfully met the demands of the surgery, helped avoid prolonged ventilation and prevent maternal respiratory complications. LESSONS: Transversus abdominis plane block with subanesthetic concentrations of sevoflurane can provide effective and safe anesthesia in the cesarean section for a patient with ALS.


Assuntos
Esclerose Amiotrófica Lateral/complicações , Cesárea/métodos , Bloqueio Nervoso/métodos , Complicações na Gravidez/patologia , Músculos Abdominais/inervação , Adulto , Anestésicos Inalatórios , Feminino , Humanos , Gravidez , Sevoflurano , Ultrassonografia de Intervenção
9.
Nat Commun ; 12(1): 5336, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504074

RESUMO

We live surrounded by vibrations generated by moving objects. These oscillatory stimuli propagate through solid substrates, are sensed by mechanoreceptors in our body and give rise to perceptual attributes such as vibrotactile pitch (i.e. the perception of how high or low a vibration's frequency is). Here, we establish a mechanistic relationship between vibrotactile pitch perception and the physical properties of vibrations using behavioral tasks, in which vibratory stimuli were delivered to the human fingertip or the mouse forelimb. The resulting perceptual reports were analyzed with a model demonstrating that physically different combinations of vibration frequencies and amplitudes can produce equal pitch perception. We found that the perceptually indistinguishable but physically different stimuli follow a common computational principle in mouse and human. It dictates that vibrotactile pitch perception is shifted with increases in amplitude toward the frequency of highest vibrotactile sensitivity. These findings suggest the existence of a fundamental relationship between the seemingly unrelated concepts of spectral sensitivity and pitch perception.


Assuntos
Percepção da Altura Sonora/fisiologia , Limiar Sensorial/fisiologia , Percepção do Tato/fisiologia , Animais , Feminino , Dedos/inervação , Dedos/fisiologia , Membro Anterior/inervação , Membro Anterior/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vibração
10.
J Physiol ; 599(21): 4865-4882, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34505294

RESUMO

Ageing is a natural process causing alterations in the neuromuscular system, which contributes to reduced quality of life. Motor unit (MU) contributes to weakness, but the mechanisms underlying reduced firing rates are unclear. Persistent inward currents (PICs) are crucial for initiation, gain control and maintenance of motoneuron firing, and are directly proportional to the level of monoaminergic input. Since concentrations of monoamines (i.e. serotonin and noradrenaline) are reduced with age, we sought to determine if estimates of PICs are reduced in older (>60 years old) compared to younger adults (<35 years old). We decomposed MU spike trains from high-density surface electromyography over the biceps and triceps brachii during isometric ramp contractions to 20% of maximum. Estimates of PICs (ΔFrequency; or simply ΔF) were computed using the paired MU analysis technique. Regardless of the muscle, peak firing rates of older adults were reduced by ∼1.6 pulses per second (pps) (P = 0.0292), and ΔF was reduced by ∼1.9 pps (P < 0.0001), compared to younger adults. We further found that age predicted ΔF in older adults (P = 0.0261), resulting in a reduction of ∼1 pps per decade, but there was no relationship in younger adults (P = 0.9637). These findings suggest that PICs are reduced in the upper limbs of older adults during submaximal isometric contractions. Reduced PIC magnitude represents one plausible mechanism for reduced firing rates and function in older individuals, but further work is required to understand the implications in other muscles and during a variety of motor tasks. KEY POINTS: Persistent inward currents play an important role in the neural control of human movement and are influenced by neuromodulation via monoamines originating in the brainstem. During ageing, motor unit firing rates are reduced, and there is deterioration of brainstem nuclei, which may reduce persistent inward currents in alpha motoneurons. Here we show that estimates of persistent inward currents (ΔF) of both elbow flexor and extensor motor units are reduced in older adults. Estimates of persistent inward currents have a negative relationship with age in the older adults, but not in the young. This novel mechanism may play a role in the alteration of motor firing rates that occurs with ageing, which may have consequences for motor control.


Assuntos
Contração Isométrica , Neurônios Motores/fisiologia , Músculo Esquelético , Adulto , Cotovelo , Eletromiografia , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Extremidade Superior
11.
Nature ; 597(7875): 250-255, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34497389

RESUMO

The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.


Assuntos
Envelhecimento , Sistema Nervoso Entérico/citologia , Feto/citologia , Saúde , Intestinos/citologia , Intestinos/crescimento & desenvolvimento , Linfonodos/citologia , Linfonodos/crescimento & desenvolvimento , Adulto , Animais , Criança , Doença de Crohn/patologia , Conjuntos de Dados como Assunto , Sistema Nervoso Entérico/anatomia & histologia , Sistema Nervoso Entérico/embriologia , Sistema Nervoso Entérico/crescimento & desenvolvimento , Células Epiteliais/citologia , Feminino , Feto/anatomia & histologia , Feto/embriologia , Humanos , Intestinos/embriologia , Intestinos/inervação , Linfonodos/embriologia , Linfonodos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Organogênese , Receptores de IgG/metabolismo , Transdução de Sinais , Análise Espaço-Temporal , Fatores de Tempo
12.
Neuron ; 109(19): 3164-3177.e8, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34499856

RESUMO

Modern brain-machine interfaces can return function to people with paralysis, but current upper extremity brain-machine interfaces are unable to reproduce control of individuated finger movements. Here, for the first time, we present a real-time, high-speed, linear brain-machine interface in nonhuman primates that utilizes intracortical neural signals to bridge this gap. We created a non-prehensile task that systematically individuates two finger groups, the index finger and the middle-ring-small fingers combined. During online brain control, the ReFIT Kalman filter could predict individuated finger group movements with high performance. Next, training ridge regression decoders with individual movements was sufficient to predict untrained combined movements and vice versa. Finally, we compared the postural and movement tuning of finger-related cortical activity to find that individual cortical units simultaneously encode multiple behavioral dimensions. Our results suggest that linear decoders may be sufficient for brain-machine interfaces to execute high-dimensional tasks with the performance levels required for naturalistic neural prostheses.


Assuntos
Interfaces Cérebro-Computador , Dedos/fisiologia , Movimento/fisiologia , Próteses Neurais , Algoritmos , Animais , Fenômenos Biomecânicos , Eletrodos Implantados , Dedos/inervação , Previsões , Modelos Lineares , Macaca mulatta , Masculino , Microeletrodos , Córtex Motor/fisiologia , Postura/fisiologia , Desenho de Prótese , Desempenho Psicomotor
13.
J Comput Assist Tomogr ; 45(5): 759-764, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34546681

RESUMO

OBJECTIVE: The purposes of this study were to determine reliable diffusion-weighted magnetic resonance neurography (DW-MRN) features of hourglass-like constriction of the upper limb nerve and to evaluate the application value of DW-MRN compared with ultrasonography (US). METHODS: We retrospectively reviewed MRN studies of 13 patients. Qualitative and quantitative image analyses were carried out. The number of constrictions based on DW-MRN and US findings was compared. RESULTS: Of the 13 cases, there were 7 cases with radial nerve abnormalities, 4 with median nerve abnormalities, and 2 with radial and median nerve abnormalities. Diffusion-weighted MRN showed a single-segmental constriction in 7 of 13 cases and multisegmental constrictions in 6 of 13 cases; the hourglass-like constriction appeared in all cases (13 of 13). Thirty-three nerve constrictions were found in DW-MRN, and 29 nerve constrictions were found in US. CONCLUSIONS: Diffusion-weighted MRN is a noninvasive and helpful diagnostic for hourglass-like constriction of the upper limb nerve.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/patologia , Adolescente , Adulto , Constrição , Feminino , Humanos , Masculino , Nervo Mediano/diagnóstico por imagem , Nervo Mediano/patologia , Pessoa de Meia-Idade , Nervo Radial/diagnóstico por imagem , Nervo Radial/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Ultrassonografia , Extremidade Superior/diagnóstico por imagem , Extremidade Superior/inervação , Extremidade Superior/patologia , Adulto Jovem
14.
FASEB J ; 35(10): e21899, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34569661

RESUMO

The cornea of the eye differs from other mucosal surfaces in that it lacks a viable bacterial microbiome and by its unusually high density of sensory nerve endings. Here, we explored the role of corneal nerves in preventing bacterial adhesion. Pharmacological and genetic methods were used to inhibit the function of corneal sensory nerves or their associated transient receptor potential cation channels TRPA1 and TRPV1. Impacts on bacterial adhesion, resident immune cells, and epithelial integrity were examined using fluorescent labeling and quantitative confocal imaging. TRPA1/TRPV1 double gene-knockout mice were more susceptible to adhesion of environmental bacteria and to that of deliberately-inoculated Pseudomonas aeruginosa. Supporting the involvement of TRPA1/TRPV1-expressing corneal nerves, P. aeruginosa adhesion was also promoted by treatment with bupivacaine, or ablation of TRPA1/TRPV1-expressing nerves using RTX. Moreover, TRPA1/TRPV1-dependent defense was abolished by enucleation which severs corneal nerves. High-resolution imaging showed normal corneal ultrastructure and surface-labeling by wheat-germ agglutinin for TRPA1/TRPV1 knockout murine corneas, and intact barrier function by absence of fluorescein staining. P. aeruginosa adhering to corneas after perturbation of nerve or TRPA1/TRPV1 function failed to penetrate the surface. Single gene-knockout mice showed roles for both TRPA1 and TRPV1, with TRPA1-/- more susceptible to P. aeruginosa adhesion while TRPV1-/- corneas instead accumulated environmental bacteria. Corneal CD45+/CD11c+ cell responses to P. aeruginosa challenge, previously shown to counter bacterial adhesion, also depended on TRPA1/TRPV1 and sensory nerves. Together, these results demonstrate roles for corneal nerves and TRPA1/TRPV1 in corneal resistance to bacterial adhesion in vivo and suggest that the mechanisms involve resident immune cell populations.


Assuntos
Aderência Bacteriana , Córnea , Pseudomonas aeruginosa/metabolismo , Canal de Cátion TRPA1/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Córnea/inervação , Córnea/metabolismo , Córnea/microbiologia , Feminino , Masculino , Camundongos , Camundongos Knockout , Canal de Cátion TRPA1/genética , Canais de Cátion TRPV/genética
15.
Nutrients ; 13(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34578826

RESUMO

Maslinic acid (MA) is a pentacyclic triterpene abundant in olive peels. MA reportedly increases skeletal muscle mass and strength in older adults; however, the underlying mechanism is unknown. This study aimed to investigate the effects of MA on denervated muscle atrophy and strength and to explore the underlying molecular mechanism. Mice were fed either a control diet or a 0.27% MA diet. One week after intervention, the sciatic nerves of both legs were cut to induce muscle atrophy. Mice were examined 14 days after denervation. MA prevented the denervation-induced reduction in gastrocnemius muscle mass and skeletal muscle strength. Microarray gene expression profiling in gastrocnemius muscle demonstrated several potential mechanisms for muscle maintenance. Gene set enrichment analysis (GSEA) revealed different enriched biological processes, such as myogenesis, PI3/AKT/mTOR signaling, TNFα signaling via NF-κB, and TGF-ß signaling in MA-treated mice. In addition, qPCR data showed that MA induced Igf1 expression and suppressed the expressions of Atrogin-1, Murf1 and Tgfb. Altogether, our results suggest the potential of MA as a new therapeutic and preventive dietary ingredient for muscular atrophy and strength.


Assuntos
Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Triterpenos/farmacologia , Animais , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Denervação Muscular/métodos , Desenvolvimento Muscular/genética , Músculo Esquelético/inervação , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Doenças Musculares/patologia , NF-kappa B/metabolismo , Olea/química , Nervo Isquiático/lesões , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
PLoS One ; 16(9): e0256720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34520462

RESUMO

BACKGROUND: Back and lower limb pain have a major impact on physical function and quality of life. While obesity is a modifiable risk factor for musculoskeletal pain, the role of adiposity is less clear. This systematic review aimed to examine the relationship between both adiposity and its distribution and back and lower limb pain. METHODS: A systematic search of electronic databases was conducted to identify studies that examined the association between anthropometric and/or direct measures of adiposity and site specific musculoskeletal pain. Risk of bias was assessed and a best evidence synthesis was performed. RESULTS: A total of 56 studies were identified which examined 4 pain regions, including the lower back (36 studies), hip (two studies), knee (13 studies) and foot (eight studies). 31(55%) studies were assessed as having low to moderate risk of bias. 17(30%) studies were cohort in design. The best evidence synthesis provided evidence of a relationship between central adiposity and low back and knee pain, but not hip or foot pain. There was also evidence of a longitudinal relationship between adiposity and the presence of back, knee and foot pain, as well as incident and increasing foot pain. CONCLUSIONS: This systematic review provides evidence of an association between both body fat and its central distribution and low back and knee pain, and a longitudinal relationship between adiposity and back, knee and foot pain. These results highlight the potential for targeting adiposity in the development of novel treatments at these sites.


Assuntos
Adiposidade , Dor Lombar/fisiopatologia , Dor Musculoesquelética/fisiopatologia , Obesidade/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Antropometria , Índice de Massa Corporal , Estudos de Coortes , Humanos , Articulação do Joelho/fisiopatologia , Perna (Membro)/inervação , Perna (Membro)/fisiopatologia , Dor Lombar/complicações , Dor Musculoesquelética/complicações , Obesidade/complicações , Osteoartrite do Joelho/complicações , Medição da Dor , Qualidade de Vida/psicologia , Fatores de Risco
17.
PLoS One ; 16(9): e0256753, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34469470

RESUMO

Dexterous use of the hands depends critically on sensory feedback, so it is generally agreed that functional supplementary feedback would greatly improve the use of hand prostheses. Much research still focuses on improving non-invasive feedback that could potentially become available to all prosthesis users. However, few studies on supplementary tactile feedback for hand prostheses demonstrated a functional benefit. We suggest that confounding factors impede accurate assessment of feedback, e.g., testing non-amputee participants that inevitably focus intently on learning EMG control, the EMG's susceptibility to noise and delays, and the limited dexterity of hand prostheses. In an attempt to assess the effect of feedback free from these constraints, we used silicone digit extensions to suppress natural tactile feedback from the fingertips and thus used the tactile feedback-deprived human hand as an approximation of an ideal feed-forward tool. Our non-amputee participants wore the extensions and performed a simple pick-and-lift task with known weight, followed by a more difficult pick-and-lift task with changing weight. They then repeated these tasks with one of three kinds of audio feedback. The tests were repeated over three days. We also conducted a similar experiment on a person with severe sensory neuropathy to test the feedback without the extensions. Furthermore, we used a questionnaire based on the NASA Task Load Index to gauge the subjective experience. Unexpectedly, we did not find any meaningful differences between the feedback groups, neither in the objective nor the subjective measurements. It is possible that the digit extensions did not fully suppress sensation, but since the participant with impaired sensation also did not improve with the supplementary feedback, we conclude that the feedback failed to provide relevant grasping information in our experiments. The study highlights the complex interaction between task, feedback variable, feedback delivery, and control, which seemingly rendered even rich, high-bandwidth acoustic feedback redundant, despite substantial sensory impairment.


Assuntos
Membros Artificiais , Retroalimentação Sensorial/fisiologia , Mãos/fisiologia , Desenho de Prótese/instrumentação , Silicones , Adulto , Feminino , Mãos/inervação , Voluntários Saudáveis , Humanos , Masculino , Desenho de Prótese/métodos , Desempenho Psicomotor , Tato/fisiologia , Adulto Jovem
18.
PLoS One ; 16(9): e0256723, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473788

RESUMO

INTRODUCTION: Motor Imagery (MI) is a powerful tool to stimulate sensorimotor brain areas and is currently used in motor rehabilitation after a stroke. The aim of our study was to evaluate whether an illusion of movement induced by visuo-proprioceptive immersion (VPI) including tendon vibration (TV) and Virtual moving hand (VR) combined with MI tasks could be more efficient than VPI alone or MI alone on cortical excitability assessed using Electroencephalography (EEG). METHODS: We recorded EEG signals in 20 healthy participants in 3 different conditions: MI tasks involving their non-dominant wrist (MI condition); VPI condition; and VPI with MI tasks (combined condition). Each condition lasted 3 minutes, and was repeated 3 times in randomized order. Our main judgment criterion was the Event-Related De-synchronization (ERD) threshold in sensori-motor areas in each condition in the brain motor area. RESULTS: The combined condition induced a greater change in the ERD percentage than the MI condition alone, but no significant difference was found between the combined and the VPI condition (p = 0.07) and between the VPI and MI condition (p = 0.20). CONCLUSION: This study demonstrated the interest of using a visuo-proprioceptive immersion with MI rather than MI alone in order to increase excitability in motor areas of the brain. Further studies could test this hypothesis among patients with stroke to provide new perspectives for motor rehabilitation in this population.


Assuntos
Excitabilidade Cortical/fisiologia , Retroalimentação Sensorial/fisiologia , Movimento/fisiologia , Propriocepção/fisiologia , Córtex Sensório-Motor/fisiologia , Adulto , Interfaces Cérebro-Computador , Eletroencefalografia , Feminino , Mãos/inervação , Mãos/fisiologia , Voluntários Saudáveis , Humanos , Imagens, Psicoterapia/métodos , Imaginação/fisiologia , Masculino , Pessoa de Meia-Idade , Córtex Sensório-Motor/diagnóstico por imagem , Articulação do Punho/inervação , Articulação do Punho/fisiologia
19.
Am J Physiol Gastrointest Liver Physiol ; 321(5): G513-G526, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34523347

RESUMO

Postprandial orthostasis activates mechanisms of cardiovascular homeostasis to maintain normal blood pressure (BP) and adequate blood flow to vital organs. The underlying mechanisms of cardiovascular homeostasis in postprandial orthostasis still require elucidation. Fourteen healthy volunteers were recruited to investigate the effect of an orthostatic challenge (60°-head-up-tilt for 20 min) on splanchnic and systemic hemodynamics before and after ingesting an 800-kcal composite meal. The splanchnic circulation was assessed by ultrasonography of the superior mesenteric and hepatic arteries and portal vein. Systemic hemodynamics were assessed noninvasively by continuous monitoring of BP, heart rate (HR), cardiac output (CO), and the pressor response to an intravenous infusion on increasing doses of phenylephrine, an α1-adrenoceptor agonist. Neurohumoral regulation was assessed by spectral analysis of HR and BP, plasma catecholamine and aldosterone levels and plasma renin activity. Postprandial mesenteric hyperemia was associated with an increase in CO, a decrease in SVR and cardiac vagal tone, and reduction in baroreflex sensitivity with no change in sympathetic tone. Arterial α1-adrenoceptor responsiveness was preserved and reduced in hepatic sinusoids. Postprandial orthostasis was associated with a shift of 500 mL of blood from mesenteric to systemic circulation with preserved sympathetic-mediated vasoconstriction. Meal ingestion provokes cardiovascular hyperdynamism, cardiac vagolysis, and resetting of the baroreflex without activation of the sympathetic nervous system. Meal ingestion also alters α1-adrenoceptor responsiveness in the hepatic sinusoids and participates in the redistribution of blood volume from the mesenteric to the systemic circulation to maintain a normal BP during orthostasis.NEW & NOTEWORTHY A unique integrated investigation on the effect of meal on neurohumoral mechanisms and blood flow redistribution of the mesenteric circulation during orthostasis was investigated. Food ingestion results in cardiovascular hyperdynamism, reduction in cardiac vagal tone, and baroreflex sensitivity and causes a decrease in α1-adrenoceptor responsiveness only in the venous intrahepatic sinusoids. About 500-mL blood shifts from the mesenteric to the systemic circulation during orthostasis. Accordingly, the orthostatic homeostatic mechanisms are better understood.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Tontura/fisiopatologia , Hemodinâmica , Período Pós-Prandial , Receptores Adrenérgicos alfa 1/metabolismo , Circulação Esplâncnica , Agonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Adulto , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/metabolismo , Velocidade do Fluxo Sanguíneo , Sistema Cardiovascular/inervação , Tontura/diagnóstico por imagem , Tontura/metabolismo , Feminino , Voluntários Saudáveis , Hemodinâmica/efeitos dos fármacos , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/fisiopatologia , Humanos , Infusões Intravenosas , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Artéria Mesentérica Superior/fisiopatologia , Pessoa de Meia-Idade , Fenilefrina/administração & dosagem , Veia Porta/diagnóstico por imagem , Veia Porta/fisiopatologia , Receptores Adrenérgicos alfa 1/efeitos dos fármacos , Transdução de Sinais , Fatores de Tempo , Adulto Jovem
20.
Biomed Res Int ; 2021: 9956609, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527746

RESUMO

Objective: Schizencephaly is a rare congenital malformation that causes motor impairment. To determine the treatment strategy, each domain of the motor functions should be appropriately evaluated. We correlated a color map of diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS) with the hand function test (HFT) to identify the type of hand function that each test (DTI and TMS) reflects. Further, we attempted to demonstrate the motor neuron organization in schizencephaly. Method: This retrospective study was conducted on 12 patients with schizencephaly. TMS was conducted in the first dorsal interosseous (FDI), biceps (BB), and deltoid muscles of the upper extremity, and contralateral MEP (cMEP) and ipsilateral MEP (iMEP) were recorded. The HFT included the grip strength, box and block (B&B), and 9-hole peg test. The schizencephalic cleft was confirmed using magnetic resonance imaging, and the corticospinal tract (CST) was identified using the color map of DTI. The symmetry indices for the peduncle and CST at pons level were calculated as the ratios of the cross-sectional area of the less-affected side and that of the more-affected side. Result: In the more-affected hemisphere TMS, no iMEP was obtained. In the less-affected hemisphere TMS, the iMEP response was detected in 9 patients and cMEP in all patients, which was similar to the pattern observed in unilateral lesion. Paretic hand grip strength was strongly correlated with the presence of iMEP (p = 0.044). The symmetry index of the color map of DTI was significantly correlated with the B&B (p = 0.008, R 2 = 0.416), whereas the symmetry index of the peduncle was not correlated with all HFTs. Conclusion: In patients with schizencephaly, the iMEP response rate is correlated with the hand function related to strength, while the symmetricity of the CST by the color map of DTI is correlated with the hand function associated with dexterity. Additionally, we suggest the possible motor organization pattern of schizencephaly following interhemispheric competition.


Assuntos
Pedúnculo Cerebral/patologia , Mãos/fisiopatologia , Córtex Motor/patologia , Ponte/patologia , Transtornos Psicomotores/patologia , Tratos Piramidais/patologia , Esquizencefalia/patologia , Adolescente , Adulto , Mapeamento Encefálico , Pedúnculo Cerebral/diagnóstico por imagem , Pedúnculo Cerebral/fisiopatologia , Criança , Pré-Escolar , Imagem de Tensor de Difusão/métodos , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Córtex Motor/fisiopatologia , Músculo Esquelético/inervação , Músculo Esquelético/fisiopatologia , Ponte/diagnóstico por imagem , Ponte/fisiopatologia , Transtornos Psicomotores/diagnóstico por imagem , Transtornos Psicomotores/fisiopatologia , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/fisiopatologia , Estudos Retrospectivos , Esquizencefalia/diagnóstico por imagem , Esquizencefalia/fisiopatologia , Estimulação Magnética Transcraniana/métodos
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