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Multiple sclerosis (MS) is the most common demyelinating disease affecting the central nervous system. It has a wide range of manifestations and commonly affects the visual system. Many patients with MS report decreased vision, diplopia, nystagmus, and abnormal ocular motility. Nevertheless, bilateral horizontal gaze palsies are exceptionally rarely seen. We present the case of a 24-year-old female who came to our pediatric ophthalmology clinic complaining of bilateral horizontal gaze palsy, photophobia, and eye pain for 2 days. Although the patient had a family history of MS, there was no similar or previous complaint, with an unremarkable past medical and surgical history. During the examination, she was found to have a complete bilateral absence of horizontal saccade and pursuit, with slight limitations in vertical ones. There was no nystagmus or skew deviation, and the rest of the cranial nerves (CNs) were intact. Her ocular vital signs were normal, and her corrected visual acuity was 20/20 with full-color vision. The rest of the physical and neurological examinations were unremarkable. After referral to neurology, the magnetic resonance imaging showed multiple hyperintense lesions in deep white matter, pons, and midbrain. The correlation of imaging findings with clinical presentation confirmed the diagnosis of a clinically isolated syndrome. Extra-ocular motility (EOM) significantly improved after pulse steroid therapy and five sessions of plasma exchange, but the patient developed 35 prism diopter of acquired concomitant esotropia. She underwent a right medial rectus botulinum toxin injection which dramatically improved her condition, and became orthotropic during the last 2 months of follow-up after the injection.
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We report a case of bilateral horizontal conjugate gaze palsy due to a dorsal median pontine haemorrhage. The development of horizontal gaze palsy has been attributed to lesions in the pontine tegmentum, and in this case, has occurred in conjunction with other features as part of Foville's syndrome. Complete horizontal gaze palsy is a rare clinical manifestation as bilateral involvement is unusual. Our case provides further insight into the intricacies of the brainstem neuroanatomy through a description of the involved neural pathways and nuclei accounting for complex neurological manifestations in one patient.
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Here, we report a case of an 85-year-old man who presented sudden onset of diplopia, dysarthria, and gait disturbance. On admission, he exhibited bilateral adduction palsy, convergence palsy, and binocular exotropia in the forward gaze showing wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome. He had a history of chronic nonvalvular atrial fibrillation. DWI-MRI revealed acute ischemic lesions in the paramedian pontine tegmentum, lower midbrain, both cerebellar hemispheres, and left frontal cortex. He was thus diagnosed with an acute phase of cardioembolic stroke. Subsequently, the right eye adduction palsy in the forward gaze was slightly improved, but other eye movement disorders persisted during discharge from the hospital. The pathology was suspected to involve bilateral damages to both medial longitudinal fasciculus and the paramedian pontine reticular formation. WEBINO syndrome was not only ascribed to lacunar infarction and large artery atherosclerosis but also cardioembolic stroke. The presence of other non-eye symptoms and multiple ischemic lesions could be the characteristics of WEBINO syndrome following cardioembolic stroke.
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AVC Embólico , Exotropia , Transtornos da Motilidade Ocular , Oftalmoplegia , Acidente Vascular Cerebral , Idoso de 80 Anos ou mais , Exotropia/etiologia , Humanos , Masculino , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/etiologia , Oftalmoplegia/etiologia , Paralisia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , SíndromeRESUMO
INTRODUCTION: Surgical approaches to intrinsic pontine lesions are technically difficult and prone to complications. The surgical approach to the brainstem through midline pontine splitting is regarded as safe since there are no crossing vital fibers in the midline between the abducens nuclei at the facial colliculi in the pons and the oculomotor nucleus in the midbrain, although its actual utilization has not been reported previously. CASE PRESENTATION: A 6-year-old boy presented with a large intrinsic cystic lesion in the pons. We successfully achieved gross total removal via the median sulcus of the fourth ventricle. The fixation in adduction and limitation of abduction were newly observed in the left eye after surgery. DISCUSSION: The advantage of the surgical approach through the median sulcus is the longer line of dissection in an axial direction and the gain of a wider operative view. On the other hand, the disadvantage of this approach is the limited orientation and view toward lateral side and a possible impairment of the medial longitudinal fasciculi and paramedian pontine reticular formation, which are located lateral to the midline sulcus bilaterally and are easily affected via the median sulcus of the fourth ventricular floor. Ongoing developments in intraoperative neuro-monitoring and navigation systems are expected to enhance this promising approach, resulting in a safer and less complicated procedure in the future. CONCLUSION: The surgical approach through midline pontine splitting is suitable for midline and deep locations of relatively large pontine lesions that necessitate a wider surgical window.
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Tronco Encefálico , Ponte , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/cirurgia , Criança , Quarto Ventrículo/diagnóstico por imagem , Quarto Ventrículo/cirurgia , Humanos , Masculino , Ponte/diagnóstico por imagem , Ponte/cirurgiaRESUMO
RESUMEN Introducción: El manejo diagnóstico y terapéutico en los pacientes con lupus eritematoso sistémico que desarrollan una afectación neuropsiquiátrica representa un reto, debido a la heterogeneidad de las formas en que puede presentarse y la ausencia de criterios diagnósticos. Objetivo: Reconocer las formas clínicas de presentación de los síndromes neuroftalmológicos que traducen afectación pontina. Presentación del caso: Hombre de 71 años con antecedente de lupus eritematoso sistémico con afectación neuopsiquiátrica, que de forma aguda desarrolla un cuadro emético en el curso de una emergencia hipertensiva seguido de una parálisis de la mirada horizontal hacia la izquierda, una oftalmoplejía internuclear posterior derecha y una parálisis facial izquierda. En la neuroimagen se constata una afectación multifocal con marcado daño pontino. Conclusiones: Reconocer las formas clínicas de presentación de estos trastornos neuroftalmológicos raros que generalmente se presentan de forma aguda/subaguda permite al neurólogo realizar el diagnóstico topográfico de la lesión a nivel protuberancial con elevada precisión desde la Sala de Urgencias, así como reducir los posibles diagnósticos diferenciales a una etiología vascular, desmielinizante u ocupativa de espacio(AU)
ABSTRACT Introduction: The diagnostic and therapeutic management of patients with systemic lupus erythematosus who develop a neuropsychiatric involvement represents one of the biggest challenges due to the heterogeneity of the ways in which it can occur and the absence of diagnostic criteria. Objective: To recognize the clinical forms of presentation of neurophthalmological syndromes that express pontine involvement. Case presentation: Seventy-one-year-old man with history of systemic lupus erythematosus with neuropsychiatric involvement who acutely develops an emetic episode in the course of a hypertensive emergency followed by a paralysis of the horizontal gaze to the left, a right-sided posterior internuclear ophthalmoplegia and a left facial palsy. In the neuroimaging, a multifocal involvement with marked pontine damage is observed. Conclusions: Recognizing the clinical forms of presentation of these rare neurophthalmological disorders that generally occur in an acute or subacute form allows the neurologist to perform the topographic diagnosis of the lesion at a protuberancial level with high precision from the time when the patient attends the Emergency Department and reduces the possible differential diagnoses to a vascular, demyelinating or occupational etiology of space(AU)
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Humanos , Masculino , Idoso , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Lúpus Eritematoso Sistêmico/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Diagnóstico DiferencialAssuntos
Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Técnicas de Diagnóstico Oftalmológico , Oftalmoplegia/diagnóstico por imagem , Oftalmoplegia/etiologia , Idoso , Hemorragia Cerebral/cirurgia , Craniotomia/métodos , Técnicas de Diagnóstico Oftalmológico/instrumentação , Feminino , Humanos , Oftalmoplegia/cirurgiaRESUMO
BACKGROUND: Demyelinating central nervous system diseases include several disorders that multiple sclerosis (MS) is identified as the most common among them. Ocular movement disturbances are a typical presentation in MS patients where lesions affect the complex and interconnected pathways involved in eye motion. Centers for gaze control are located in the pons primarily; therefore, lesions involving these centers can be presented with abnormalities in gaze. However, bilateral lesions in pontine gaze centers are exceptionally rare. CASE PRESENTATION: A 16-year-old girl with bilateral horizontal gaze palsy was referred to the neurology clinic. Magnetic resonance imaging of the patient indicated bilateral hyperintensities in the pons at the level of the paramedian pontine reticular formation. The patient was diagnosed with multiple sclerosis with respect to clinical and imaging findings and managed. CONCLUSION: Ocular movement abnormalities are a commonly encountered manifestation in patients with multiple sclerosis, however, bilateral gaze palsy is an exceptionally rare sign and should guide the physician to contemplate for anticipated lesions in the pons, and suspect MS, especially in childbearing-aged women. Although an extensive workup should also be done to rule out possible mimickers.
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Esclerose Múltipla/complicações , Esclerose Múltipla/patologia , Transtornos da Motilidade Ocular/etiologia , Tegmento Pontino/patologia , Adolescente , Feminino , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome has previously been reported in only 2 patients with progressive supranuclear palsy (PSP). Herein, we report a third case of WEBINO syndrome with PSP. The patient was an 81-year-old man who had experienced gradually increasing gait disturbance and occasional falls since the age of 78 years. At 80 years of age, he presented with cognitive impairment, parkinsonism, and oculomotor abnormalities. The oculomotor abnormalities consisted of vertical gaze palsy and loss of eye convergence. Brain magnetic resonance imaging demonstrated marked atrophy of the midbrain. He was diagnosed with PSP. At the age of 81 years, he presented with alternating extropia in his forward gaze and adduction paresis and outward nystagmus of the abducted eye in his horizontal gaze, both of which were compatible with WEBINO syndrome. Previously, we reported the first case of PSP with WEBINO syndrome, and another group recently reported a second case. In light of the previous cases and the present case, WEBINO syndrome in PSP should not be considered extremely rare. Furthermore, WEBINO syndrome has not been reported in other neurodegenerative disorders, which suggests that it might be a useful and specific diagnostic finding in PSP.
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The first study of Constantin von Economo on the mammalian brain was published in 1902. Experiments were carried out in rabbits at the Physiological Institute headed by Siegmund von Exner-Ewarten in Vienna to investigate the central pathways of chewing and swallowing. After placing cortical lesions, Economo applied cortical and subcortical electrical stimulation to obtain masticatory movements, and tracked degenerated fibers by means of the Marchi method. He traced fibers through the internal capsule, ventral nucleus of the thalamus, subthalamic nucleus, substantia nigra and its connections with the motor nucleus of the trigeminal nerve, and nucleus solitarius. He suggested that the substantia nigra is responsible for coordinating alimentation movements, with the involvement of cranial nerves V, VII, IX and X as well. We discuss these findings in a historical and a modern perspective, including the concept of a central pattern generator in the pontine reticular formation and its interaction with the nucleus solitarius. Today we understand that mastication is a voluntary action controlled by motor cortical areas, by motoneurons of the trigeminal, and by a neural pattern generator in the pons. On the other hand, deglutition comprises 'reflex swallowing' triggered by sensory fibers of cranial nerves V, IX and X, and 'voluntary swallowing' which may be controlled by both cortical fields and subcortical areas, such as the internal capsule, the hypothalamus and the mesencephalic reticular formation.
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Deglutição/fisiologia , Mastigação/fisiologia , Vias Neurais/fisiologia , Neurologia/história , Médicos , Animais , Áustria , Encéfalo/citologia , Encéfalo/fisiologia , Mapeamento Encefálico/história , Mapeamento Encefálico/métodos , Mapeamento Encefálico/veterinária , Embrião de Galinha , Eletrofisiologia/história , História do Século XIX , Humanos , Médicos/história , Editoração/históriaRESUMO
We present three cases that we suggest require a novel diagnosis and a reconsideration of current understandings of pontine anatomy. In this case series, we highlight a series of patients with monophasic, fully recovering inflammatory lesions in the pontine tegmentum not due to any of the currently recognized causes of this syndrome. We highlight other similar cases in the literature and suggest there may be a particular epitope for an as-yet-undiscovered antibody underlying the tropism for this area. We highlight the potential harm of misdiagnosis with relapsing inflammatory or other serious diagnoses with significant adverse impact on the patient. In addition, we propose that this would support a reinterpretation of the currently accepted anatomy of the pontine gaze inputs to the median longitudinal fasciculus and paramedian pontine reticular formation.
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Ataxia/genética , Ataxia/fisiopatologia , Canais de Cálcio/genética , Códon sem Sentido , Nistagmo Patológico/genética , Nistagmo Patológico/fisiopatologia , Acompanhamento Ocular Uniforme/genética , Acompanhamento Ocular Uniforme/fisiologia , Adulto , Fenômenos Biomecânicos , Humanos , MasculinoRESUMO
El estudio de las estrategias neurales para la organización del comportamiento en vertebrados constituye un desafío mayor para la Neurociencia. El avance del conocimiento en este campo depende de manera crítica de la utilización de modelos experimentales adecuados que admitan múltiples niveles de análisis (p.ej: comportamental, circuital, celular, sináptico, molecular) y abordajes multitécnicos. Nos propusimos analizar in vitro una red neural de la unión mesopontina del tronco encefálico críticamente implicada en el control del sueño de movimientos oculares rápidos (S-REM). Pese al cúmulo de evidencias que apoyan el papel desempeñado por esta red en relación al S-REM, los mecanismos celulares y sinápticos que subyacen a este control son poco conocidos y continúan siendo objeto de intensa investigación. Para avanzar en el conocimiento de estos mecanismos, se llevó a cabo la caracterización morfológica y funcional de una rodaja de tronco encefálico de la rata, en la que las estructuras críticas para el control del S-REM, i.e.: núcleos tegmentales laterodorsal y pedúnculopontino, y su proyección al núcleo reticular pontis oralis (PnO), están presentes y son operativas. La inclusión del núcleo motor del trigémino en la rodaja permitió detectar cambios de la excitabilidad de las motoneuronas ante manipulaciones farmacológicas del PnO, representativos de los cambios del tono muscular asociados a maniobras similares realizadas in vivo. La utilización de este modelo in vitro de S-REM, permitirá aportar a la dilucidación de las estrategias neurales que operan en niveles intermedios de organización del SN en mamíferos para la generación y regulación de un estado comportamental.
The study of the neural basis of behavior is a major challenge in Neuroscience. Advancing our knowledge in this field depends, critically, on the use of experimental paradigms that provide multiple levels of analysis, as well as powerful techniques. We have selected, as a model of a neural plan that organizes a complex behavior, a neural network located in the mesopontine junction. This region is thought to be both necessary and sufficient for the generation of rapid eye movement (REM) sleep, although the cellular and synaptic mechanisms involved in the control of this behavioral state at the mesopontine level are still under debate and remain poorly understood. As part of a long term effort to gain insight into these mechanisms, we carried out the morphological and functional characterization of a slice preparation of rat brainstem and we demonstrate that critical structures for the control of REM sleep - the laterodorsal and pedunculopontine tegmental nuclei and their projection to the oral part of the pontine reticular nucleus (PnO) - are present and are operational. The presence of the trigeminal motor nucleus in the slice sought to include in the experimental model a structure capable of expressing changes of the excitability of the motorneurons caused by pharmacological manipulations of the PnO, representative of changes of muscle tone associated with similar maneuvers performed in vivo. The use of this in vitro model of REM sleep will provide critical information to elucidate neural strategies that operate at intermediate levels of central nervous system organization in mammals to control behavioral states.
O estudo de estratégias neurais para a organização do comportamento em vertebrados constitui um desafio maior para a Neurociencia. O avanço do conhecimento nessa área depende criticamente da utilização de modelos experimentais adequados que suportem múltiplos níveis de análise (por exemplo: comportamental, circuital, celular, sináptico e molecular) e abordagens por múltiplas técnicas. Decidiu-se analisar in vitro uma rede neural da união mesopontina do tronco encefálico criticamente envolvida no controle do sono de movimentos oculares rápidos (S-REM). Apesar da riqueza de provas que sustentam o papel desta rede em relação ao S-REM, os mecanismos celulares e sinápticos subjacentes a este controle são pouco conhecidos e permanecem sob intensa investigação. Para avançar no conhecimento desses mecanismos, caracterizou-se morfológica e funcionalmente uma fatia de tronco encefálico de rato, na qual as estruturas críticas para o controle do S-REM, i.e.: núcleos tegmentais laterodorsal e pedunculopontino, e sua projeção para o núcleo reticular pontis oralis (PnO) estão presentes e operantes. A inclusão do núcleo motor do trigêmeo na fatia permitiu detectar mudanças da excitabilidade das motoneuronas provocadas por manipulações farmacológicas do PnO, representativas das alterações do tônus muscular associados com operações semelhantes quando realizados in vivo. A utlização deste modelo in vitro de S-REM permitirá contribuir para a elucidação de estratégias neurais que operam em níveis intermedios de organização do SN de mamíferos para a geração e regulação de um estado comportamental.
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Animais , Ratos , Sono REM/fisiologia , Vigília/fisiologia , Polissonografia , Neurônios/fisiologia , Técnicas In Vitro , Tronco Encefálico/anatomia & histologia , Ratos Wistar , Estimulação Elétrica , Fenômenos EletrofisiológicosRESUMO
Impaired consciousness occurs suddenly and unpredictably in people with epilepsy, markedly worsening quality of life and increasing risk of mortality. Focal seizures with impaired consciousness are the most common form of epilepsy and are refractory to all current medical and surgical therapies in about one-sixth of cases. Restoring consciousness during and following seizures would be potentially transformative for these individuals. Here, we investigate deep brain stimulation to improve level of conscious arousal in a rat model of focal limbic seizures. We found that dual-site stimulation of the central lateral nucleus of the intralaminar thalamus (CL) and the pontine nucleus oralis (PnO) bilaterally during focal limbic seizures restored normal-appearing cortical electrophysiology and markedly improved behavioral arousal. In contrast, single-site bilateral stimulation of CL or PnO alone was insufficient to achieve the same result. These findings support the "network inhibition hypothesis" that focal limbic seizures impair consciousness through widespread inhibition of subcortical arousal. Driving subcortical arousal function would be a novel therapeutic approach to some forms of refractory epilepsy and may be compatible with devices already in use for responsive neurostimulation. Multisite deep brain stimulation of subcortical arousal structures may benefit not only patients with epilepsy but also those with other disorders of consciousness.
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Nível de Alerta , Transtornos da Consciência/terapia , Estimulação Encefálica Profunda/métodos , Epilepsias Parciais/terapia , Convulsões/terapia , Animais , Nível de Alerta/fisiologia , Estado de Consciência/fisiologia , Transtornos da Consciência/etiologia , Transtornos da Consciência/fisiopatologia , Modelos Animais de Doenças , Epilepsias Parciais/complicações , Epilepsias Parciais/fisiopatologia , Comportamento Exploratório/fisiologia , Feminino , Núcleos Intralaminares do Tálamo/fisiopatologia , Inibição Neural/fisiologia , Ponte/fisiopatologia , Ratos Sprague-Dawley , Convulsões/complicações , Convulsões/fisiopatologiaRESUMO
"Eight-and-a-half" syndrome is a rare condition involving the ipsilateral abducens nucleus or paramedian pontine reticular formation (PPRF), the ipsilateral medial longitudinal fasciculus (MLF), and the adjacent facial colliculus/facial nerve fascicle. The condition is often caused by a lesion (vascular or demyelinating) in the dorsal tegmentum of the caudal pons. There are new variants of this syndrome caused by extension of lesion to involve new adjacent structures in pontine tegmentum. We report two patients with different etiology presenting with clinical features suggestive of eight-and-a-half syndrome associated with hemiataxia representing "nine" syndrome (8½ + ½ = 9) adding new dimension to "eight-and-a-half" syndrome.
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Pontine reticular formation (PRF) is involved in the generation and maintenance of generalized epileptic seizures. Carbenoxolone (CBX) is a gap junction blocker with anticonvulsant properties. Therefore, the present study was designed to explore the effects of CBX microinjected into the pontis caudalis nucleus (PnC) on generalized tonic-clonic seizures (GTCS) and epileptiform activity induced by pentylenetetrazole (PTZ). All control rats presented GTCS after a single dose of PTZ. The microinjection of CBX into the PnC reduced the GTCS incidence induced by PTZ. Moreover, the CBX significantly increased the latency to the first myoclonic jerk. Additionally, CBX significantly decreased the spectral power and the amplitude of the epileptiform activity induced by PTZ. By contrast, the microinjection of a gap junction opener (trimethylamine) did not cause anticonvulsant effects and even increased the duration of the GTCS. These findings suggest that the PnC is a particular nucleus where the CBX could exert its action mechanisms and elicit anticonvulsant effects.
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Anticonvulsivantes/farmacologia , Carbenoxolona/farmacologia , Epilepsia/fisiopatologia , Pentilenotetrazol , Tegmento Pontino/efeitos dos fármacos , Animais , Anticonvulsivantes/uso terapêutico , Carbenoxolona/uso terapêutico , Epilepsia/induzido quimicamente , Masculino , Microinjeções , Tegmento Pontino/fisiopatologia , Ratos Wistar , Convulsões/fisiopatologiaRESUMO
Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is an uncommon disorder of ocular motility that possesses a unique spectrum of clinical findings, consisting of primary gaze exotropia, adduction impairment and nystagmus of the abducting eye. WEBINO is a variant of internuclear ophthalmoplegia (INO) sharing similar pathophysiology and aetiologies. Much of the literature published on internuclear ophthalmoplegia and its variants focuses on aetiology and pathophysiology, whereas there has been less information addressing prognosis and management. This review will provide current perspectives on the pathogenesis, prognosis and management of WEBINO syndrome.
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Técnicas de Diagnóstico Oftalmológico , Gerenciamento Clínico , Movimentos Oculares/fisiologia , Transtornos da Motilidade Ocular , Humanos , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/fisiopatologia , Transtornos da Motilidade Ocular/terapia , PrognósticoRESUMO
The acoustic startle reflex (ASR) is a survival mechanism of alarm, which rapidly alerts the organism to a sudden loud auditory stimulus. In rats, the primary ASR circuit encompasses three serially connected structures: cochlear root neurons (CRNs), neurons in the caudal pontine reticular nucleus (PnC), and motoneurons in the medulla and spinal cord. It is well-established that both CRNs and PnC neurons receive short-latency auditory inputs to mediate the ASR. Here, we investigated the anatomical origin and functional role of these inputs using a multidisciplinary approach that combines morphological, electrophysiological and behavioral techniques. Anterograde tracer injections into the cochlea suggest that CRNs somata and dendrites receive inputs depending, respectively, on their basal or apical cochlear origin. Confocal colocalization experiments demonstrated that these cochlear inputs are immunopositive for the vesicular glutamate transporter 1 (VGLUT1). Using extracellular recordings in vivo followed by subsequent tracer injections, we investigated the response of PnC neurons after contra-, ipsi-, and bilateral acoustic stimulation and identified the source of their auditory afferents. Our results showed that the binaural firing rate of PnC neurons was higher than the monaural, exhibiting higher spike discharges with contralateral than ipsilateral acoustic stimulations. Our histological analysis confirmed the CRNs as the principal source of short-latency acoustic inputs, and indicated that other areas of the cochlear nucleus complex are not likely to innervate PnC. Behaviorally, we observed a strong reduction of ASR amplitude in monaural earplugged rats that corresponds with the binaural summation process shown in our electrophysiological findings. Our study contributes to understand better the role of neuronal mechanisms in auditory alerting behaviors and provides strong evidence that the CRNs-PnC pathway mediates fast neurotransmission and binaural summation of the ASR.
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Opsoclonus-myoclonus syndrome (OMS) is well known as a paraneoplastic syndrome or as a parainfectious neurologic complication. However, OMS associated with a neurodegenerative disorder has not been described previously. A 48-year-old woman had been diagnosed as multiple system atrophy-parkinsonian type (MSA-P) based on the findings of dopamine non-responsive parkinsonism with autonomic failure and typical findings on magnetic resonance imaging 5 years ago. She exhibited recurrent asynchronous and arrhythmic myoclonic movements of the upper limbs and abdomen with a very short duration, and involuntary eye movements, which were repetitive, rapid, random, multidirectional, conjugate saccades of irregular amplitude and frequency at rest. Based on hematological and radiological findings, the diagnosis was advanced MSA-P associated with OMS. As far as we are aware, there have not been any previous reports of such a case.
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The effects of LP-211, a selective serotonin 5-HT7 receptor agonist were studied in adult rats implanted for chronic sleep recordings. Intraperitoneal administration of LP-211 (2.5-10mg/kg) during the light phase of the light-dark cycle significantly increased wakefulness (W) and reduced rapid-eye-movement sleep (REMS) and the number of REM periods during the 6-h recording period. Direct infusion of LP-211 into the dorsal raphe nucleus (DRN) (2-6 mM), locus coeruleus nucleus (LC) (4 mM), basal forebrain (horizontal limb of the diagonal band of Broca) (HDB) (2 mM) or laterodorsal tegmental nucleus (LDT) (4 mM) induced also a decrease of REMS. Additionally, microinjection of the 5-HT7 receptor ligand into the HDB (2 mM) augmented W. Presently, there is no satisfactory explanation for the effect of 5-HT7 receptor activation on W and REMS occurrence. Additional studies are required to characterize the neurotransmitter systems responsible for the actions of LP-211 on the behavioral states.
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Sistema Nervoso Central/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Piperazinas/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Animais , Relação Dose-Resposta a Droga , Eletroencefalografia , Eletromiografia , Masculino , Microinjeções , Ratos , Ratos Wistar , Sono/efeitos dos fármacos , Fatores de Tempo , Vigília/efeitos dos fármacosRESUMO
The oral pontine reticular formation (PnO) of rat is one region identified in the brainstem as a rapid eye movement (REM) sleep induction zone. Microinjection of GABA(A) receptor antagonists into PnO induces a long lasting increase in REM sleep, which is similar to that produced by cholinergic agonists. We previously showed that this REM sleep-induction can be completely blocked by a muscarinic antagonist, indicating that the REM sleep-inducing effect of GABA(A) receptor antagonism is dependent upon the local cholinergic system. Consistent with these findings, it has been reported that GABA(A) receptor antagonists microdialyzed into PnO resulted in increased levels of acetylcholine. We hypothesize that GABA(A) receptors located on cholinergic boutons in the PnO are responsible for the REM sleep induction by GABA(A) receptor antagonists through blocking GABA inhibition of acetylcholine release. Cholinergic, varicose axon fibers were studied in the PnO by immunofluorescence and confocal, laser scanning microscopy. Immunoreactive cholinergic boutons were found to be colocalized with GABA(A) receptor subunit protein γ2. This finding implicates a specific subtype and location of GABA(A) receptors in PnO of rat in the control of REM sleep.