RESUMEN
Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits.
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Lesiones Encefálicas , Dopamina beta-Hidroxilasa , Norepinefrina , Estrés Oxidativo , Animales , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Dopamina beta-Hidroxilasa/metabolismo , Masculino , Norepinefrina/metabolismo , Norepinefrina/biosíntesis , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/inducido químicamente , Ratas Wistar , Ratas , Hierro/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Compuestos FerrososRESUMEN
La COVID-19 representa una emergencia internacional por los crecientes números de contagiados y fallecidos a nivel mundial. Los pacientes recuperados pueden sufrir afectaciones y secuelas respiratorias, cardiacas y neurológicas, lo que afecta su calidad de vida. El objetivo de este artículo consistió en reconstruir los protocolos de rehabilitación y fisioterapia respiratoria, cardiovascular, neurológica y neuromuscular para pacientes afectados por COVID-19, a partir de evidencias científicas reportadas. Para ello, se realizó una revisión bibliográfica en las principales bases de datos internacionales (PubMed, SciELO, Google Académico, ente otras). Para la búsqueda se utilizaron las palabras claves: COVID-19, síndrome de distrés respiratorio agudo, fisioterapia, rehabilitación respiratoria, Rehabilitación cardiovascular, rehabilitación neuromuscular y neurológica, en inglés y en español. Estos protocolos atribuyen mejorías significativas de las secuelas y en la calidad de vida de los pacientes. Se recomiendan ejercicios de fisioterapia respiratoria en posición decúbito-prono, entrenamiento de músculos inspiratorios, ejercicios aeróbicos y entrenamiento moderado de fuerza muscular. Los resultados de la aplicación de estos protocolos son satisfactorios en la recuperación de los pacientes.
A COVID-19 representa uma emergência internacional devido ao número crescente de pessoas infectadas e falecidas em todo o mundo. Os pacientes recuperados podem sofrer efeitos e sequelas respiratórias, cardíacas e neurológicas, o que afeta sua qualidade de vida. O objetivo deste artigo foi reconstruir os protocolos de reabilitação respiratória, cardiovascular, neurológica e neuromuscular e de fisioterapia para pacientes afetados pela COVID-19, com base em evidências científicas relatadas. Para tanto, foi realizada uma revisão bibliográfica nas principais bases de dados internacionais (PubMed, SciELO, Google Scholar, entre outras). As palavras-chave foram utilizadas para a busca: COVID-19, síndrome do desconforto respiratório agudo, fisioterapia, reabilitação respiratória, reabilitação cardiovascular, reabilitação neuromuscular e neurológica, nos idiomas inglês e espanhol. Esses protocolos atribuem melhorias significativas nas sequelas e na qualidade de vida dos pacientes. São recomendados exercícios de fisioterapia respiratória em posição prona, treinamento muscular inspiratório, exercícios aeróbicos e treinamento moderado de força muscular. Os resultados da aplicação desses protocolos são satisfatórios na recuperação dos pacientes.
The COVID-19 represents an international emergency due to the increasing numbers of infected and deceased people worldwide. Recovered patients may suffer respiratory, cardiac and neurological effects and sequelae, which affects their quality of life. The objective of this article was to reconstruct the respiratory, cardiovascular, neurological and neuromuscular rehabilitation and physiotherapy protocols for patients affected by COVID-19, based on reported scientific evidence. For it, a bibliographic review was carried out in the main international databases (PubMed, sciELO, Google Scholar, among others). The key words were used for the search: COVID-19, acute respiratory distress syndrome, physiotherapy, respiratory rehabilitation, cardiovascular rehabilitation, neuromuscular and neurological rehabilitation, in English and Spanish. These protocols attribute significant improvements in sequelae and in the quality of life of patients. Respiratory physiotherapy exercises in the prone position, inspiratory muscle training, aerobic exercises and moderate muscle strength training are recommended. The results of the application of these protocols are satisfactory in the recovery of patients.
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Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride. Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury. The aim of this study was to analyze the role of α2-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage. The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours, 3 days, and 20 days after ferrous chloride-induced cortical injury: saline, clonidine, efaroxan (a selective antagonist of α2-adrenergic receptors) and clonidine + efaroxan. The sensorimotor score, the immunohistochemical staining for α2A-adrenergic receptors, and norepinephrine levels were evaluated. Eight hours post-injury, the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased, and these effects were maintained 3 days post-injury. However, 20 days later, clonidine administration diminished norepinephrine levels in the pons compared with the sham group. This effect was accompanied by sensorimotor deficits. These effects were blocked by efaroxan. In conclusion, an increase in α2-adrenergic receptor levels was observed after injury. Clonidine restores motor deficits in rats recovering from cortical injury, an effect that was prevented by efaroxan. The underlying mechanisms involve the stimulation of hypersensitive α2-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus. The results of this study suggest that α2 receptor agonists might restore deficits or impede rehabilitation in patients with brain injury, and therefore pharmacological therapies need to be prescribed cautiously to these patients.
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Brain injury leads to an excitatory phase followed by an inhibitory phase in the brain. The clinical sequelae caused by cerebral injury seem to be a response to remote functional inhibition of cerebral nuclei located far from the motor cortex but anatomically related to the injury site. It appears that such functional inhibition is mediated by an increase in lipid peroxidation (LP). To test this hypothesis, we report data from 80 rats that were allocated to the following groups: the sham group (n = 40), in which rats received an intracortical infusion of artificial cerebrospinal fluid (CSF); the injury group (n = 20), in which rats received CSF containing ferrous chloride (FeCl2, 50 mM); and the recovery group (n = 20), in which rats were injured and allowed to recover. Beam-walking, sensorimotor and spontaneous motor activity tests were performed to evaluate motor performance after injury. Lipid fluorescent products (LFPs) were measured in the pons. The total pontine contents of glutamate (GLU), glutamine (GLN) and gamma-aminobutyric acid (GABA) were also measured. In injured rats, the motor deficits, LFPs and total GABA and GLN contents in the pons were increased, while the GLU level was decreased. In contrast, in recovering rats, none of the studied variables were significantly different from those in sham rats. Thus, motor impairment after cortical injury seems to be mediated by an inhibitory pontine response, and functional recovery may result from a pontine restoration of the GLN-GLU-GABA cycle, while LP may be a primary mechanism leading to remote pontine inhibition after cortical injury.
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Lesiones Encefálicas/fisiopatología , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Corteza Motora/fisiología , Puente/metabolismo , Recuperación de la Función , Ácido gamma-Aminobutírico/metabolismo , Animales , Peroxidación de Lípido , Masculino , Trastornos Motores/fisiopatología , Estrés Oxidativo , Ratas , Ratas WistarRESUMEN
BACKGROUND: Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disorder caused by a mutation in the ATXN7 gene. The involvement of the brainstem auditory pathway in pathogenesis of this disease has not been systematically assessed. AIM: To determine involvement of the brainstem auditory pathway in SCA7 patients and its relationship to clinical features of the disease. METHODS: In this case-control study, brainstem auditory-evoked potentials (BAEPs) were assessed in 12 SCA7 patients with clinical and molecular diagnosis, compared to 2 control groups of 16 SCA2 patients and 16 healthy controls. RESULTS: SCA7 patients exhibited significant prolongation of I-wave and III-wave latencies, whereas SCA2 patients showed increased latencies for III and V waves and I-III interpeak interval. SCA7 patients with larger I-wave latencies exhibited larger CAG repeats, earlier onset age, and higher SARA scores, but in SCA2 cases, these were not observed. CONCLUSIONS: BAEP tests revealed functional involvement of the auditory pathway in SCA7 (mainly at) peripheral portions, which gave new insights into the disease physiopathology different from SCA2 and may unravel distinct pathoanatomical effects of polyQ expansions in the central nervous system. SIGNIFICANCE: These findings offer important insights into the distinctive disease mechanisms in SCA7 and SCA2, which could be useful for differential diagnosis and designing specific precision medicine approaches for both conditions.
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Today, neurorehabilitation has become in a widely used therapeutic approach in spinocerebellar ataxias; however, there are scarce powerful clinical studies supporting this notion, and these studies require extension to other specific SCA subtypes in order to be able to form conclusions concerning its beneficial effects. Therefore, in this study, we perform for the first time a case-control pilot randomized, single-blinded, cross-sectional, and observational study to evaluate the effects of physical neurorehabilitation on the clinical and biochemical features of patients with spinocerebellar ataxia type 7 (SCA7) in 18 patients diagnosed with SCA7. In agreement with the exercise regimen, the participants were assigned to groups as follows: (a) the intensive training group, (b) the moderate training group, and (c) the non-training group (control group).We found that both moderate and intensive training groups showed a reduction in SARA scores but not INAS scores, compared with the control group (p < 0.05). Furthermore, trained patients exhibited improvement in the SARA sub-scores in stance, gait, dysarthria, dysmetria, and tremor, as compared with the control group (p < 0.05). No significant improvements were found in daily living activities, as revealed by Barthel and Lawton scales (p > 0.05). Patients under physical training exhibited significantly decreased levels in lipid-damage biomarkers and malondialdehyde, as well as a significant increase in the activity of the antioxidant enzyme PON-1, compared with the control group (p < 0.05). Physical exercise improved some cerebellar characteristics and the oxidative state of patients with SCA7, which suggest a beneficial effect on the general health condition of patients.
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Modalidades de Fisioterapia , Ataxias Espinocerebelosas/rehabilitación , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
The sensorimotor cortex and the striatum are interconnected by the corticostriatal pathway, suggesting that cortical injury alters the striatal function that is associated with skilled movements and motor learning, which are functions that may be modulated by dopamine (DA). In this study, we explored motor coordination and balance in order to investigate whether the activation of D1 receptors (D1Rs) modulates functional recovery after cortical injury. The results of the beam-walking test showed motor deficit in the injured group at 24, 48 and 96h post-injury, and the recovery time was observed at 192h after cortical injury. In the sham and injured rats, systemic administration of the D1R antagonist SCH-23390 (1mg/kg) alone at 24, 48, 96 and 192h significantly (P<0.01) increased the motor deficit, while administration of the D1R agonist SKF-38393 alone (2, 3 and 4mg/kg) at 24, 48, 96 and 192h post-injury did not produce a significant difference; however, the co-administration of SKF-38393 and SCH-23390 prevented the antagonist-induced increase in the motor deficit. The cortical+striatal injury showed significantly increased the motor deficit at 24, 48, 96 and 192h post-injury (P<0.01) but did not show recovery at 192h. In conclusion, the administration of the D1R agonist did not accelerate the motor recovery, but the activation of D1Rs maintained motor coordination, confirming that an intact striatum may be necessary for achieving recovery.
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Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D1/fisiología , Corteza Sensoriomotora/fisiología , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/metabolismo , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , Animales , Benzazepinas/metabolismo , Benzazepinas/farmacología , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/fisiopatología , Cuerpo Estriado/metabolismo , Modelos Animales de Enfermedad , Dopamina/metabolismo , Antagonistas de Dopamina/farmacología , Masculino , Corteza Motora/fisiopatología , Neostriado/metabolismo , Ratas , Ratas Wistar , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D2/metabolismo , Corteza Sensoriomotora/metabolismoRESUMEN
La Enfermedad Vascular Cerebral (EVC) es una pérdida súbita de la función neurológica como resultado de una alteración focal del flujo sanguíneo cerebral debido a una isquemia o hemorragia. La EVC se ubica como la tercera causa de muerte en Estados Unidos estando solo por debajo de la cardiopatía y el cáncer a quienes se les atribuye la mayor tasa de muertes. Este estudio de revisión busca presentar la actualidad con respecto a la epidemiología, etiología y clasificación de la EVC de acuerdo a investigaciones recientes que presentan nuevos datos, con el propósito de tener mayor conocimiento de esta enfermedad y promover que la EVC es antes que nada prevenible. Una mejor comprensión de las causas de la EVC en adultos mayores puede llegar a mejorar aspectos como el manejo clínico de los pacientes y además las estrategias de prevención y a futuro las políticas en el cuidado de la salud. En esta revisión, se explora la evidencia de estudios en sujetos humanos relacionados con nuevos factores de riesgo, métodos de prevención y finalmente como la EVC afecta el funcionamiento cognitivo en general, específicamente la memoria de trabajo, función que esta altamente relacionada con la capacidad para organizar, planear e iniciar unatarea cognitiva...(AU)
Stroke is the sudden loss of the neurologic function as a response to the lack of blood supply to the brain. Stroke is the third leading cause of death in the U.S.A. just below cardiovascular disease and cancer. The goal of this article is to present current data about epidemiology, etiology and classification of stroke according to research done in the last years. Another goal is to promote the knowledge of this illness and the fact that stroke is completely preventable. A better comprehension of stroke causes in the elderly can improve the way how health professionals handle patients and preventionstrategies. This article explores the evidence of studies in the elderly, risk factors, prevention strategies and finally how stroke affects cognitive functioning in the case of working memory which is the capacity to temporarily store and manipulate information...(AU)
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Humanos , Trastornos CerebrovascularesRESUMEN
Nowadays, a consensus has been reached that designates the functional and structural reorganization of synapses as the primary mechanisms underlying the process of recovery from brain injury. We have reported that pontine noradrenaline (NA) is increased in animals after cortical ablation (CA). The aim of the present study was to explore the noradrenergic and morphological response after sensorimotor intervention (SMI) in rats injured in the motor cortex. We used male Wistar adult rats allocated in four conditions: sham-operated, injured by cortical ablation, sham-operated with SMI and injured by cortical ablation with SMI. Motor and somatosensory performance was evaluated prior to and 20 days after surgery. During the intervening period, a 15-session, SMI program was implemented. Subsequently, total NA analysis in the pons and dentate gyrus (DG) was performed. All groups underwent histological analysis. Our results showed that NA content in the DG was reduced in the injured group versus control, and this reduction was reverted in the injured group that underwent SMI. Moreover, injured rats showed reduction in the number of granule cells in the DG and decreased dentate granule cell layer thickness. Notably, after SMI, the loss of granule cells was reverted. Locus coeruleus showed turgid cells in the injured rats. These results suggest that SMI elicits biochemical and structural modifications in the hippocampus that could reorganize the system and lead the recovery process, modulating structural and functional plasticity.
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Lesiones Encefálicas/metabolismo , Giro Dentado/metabolismo , Actividad Motora , Corteza Motora/fisiopatología , Norepinefrina/metabolismo , Propiocepción , Animales , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Lesiones Encefálicas/psicología , Giro Dentado/patología , Masculino , Movimiento , Ratas WistarRESUMEN
The striatum is known to possess high levels of D1-like and D2-like receptors (D1Rs and D2Rs, respectively). We have previously shown that selective inhibition of D1Rs increases the dopaminergic metabolic response and proposed that this effect is associated with the concomitant activation of postsynaptic D2Rs by endogenous dopamine (DA). Here, we examined whether activation of D2Rs modulates the metabolism and synthesis of DA in the striatum. We used male Wistar rats to evaluate the effects of the systemic administration of a D2R agonist (bromocriptine), a D1R antagonist (SCH-23390), and the co-administration of these compounds with pargyline on the inhibition of monoamine oxidase. DA and L-3,4-dihidroxyphenylacetic acid (DOPAC) levels and 3,4-dihydroxy-L-phenylalanine (L-DOPA) content were measured using high performance liquid chromatography. The systemic administration of SCH-23390 alone, at 0.25, 0.5, 1 or 2 mg/kg, significantly (P < 0.05) increased DOPAC levels and the DOPAC/DA ratio. At 2, 4 and 8 mg/kg, the administration of bromocriptine alone significantly (P < 0.05) decreased DOPAC levels, L-DOPA content and the DOPAC/DA ratio, whereas at 2 mg/kg, it decreased DA levels. In both groups, co-administration of either SCH-23390 or bromocriptine with pargyline decreased DOPAC levels and the DOPAC/DA ratio by approximately 70 % compared to the levels observed in the control groups. In conclusion, administration of the D2R agonist bromocriptine decreased dopaminergic synthesis and metabolism in the striatum; in contrast, administration of the D1R antagonist SCH-23390 induced the opposite effects.
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Cuerpo Estriado/efectos de los fármacos , Agonistas de Dopamina/farmacología , Dopamina/metabolismo , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D2/agonistas , Animales , Cuerpo Estriado/metabolismo , Masculino , Ratas , Ratas WistarRESUMEN
BACKGROUND: Autosomal dominant spinocerebellar ataxias (SCA) are a group of inherited neurodegenerative disorders that typically show peripheral neuropathy. SCA7 is one of the rarest forms of SCA (<1/100,000 individuals). However, the disease shows a prevalence of â¼800/100,000 inhabitants in certain regions of Mexico. This low global prevalence may explain, at least in part, the isolated anecdotal and limited clinical data regarding peripheral neuropathy in SCA7 patients. AIM: To assess sensory and motor peripheral nerve action potentials in an SCA7 patients group and in healthy volunteers, and subsequently correlate the electrophysiological findings with clinical and genetic features. MATERIALS AND METHODS: We enrolled in our study, 13 symptomatic SCA7 patients with a confirmed molecular and clinical diagnosis, and 19 healthy volunteers as the control group. Nerve conduction studies were carried out using standard electromyography recording methods. The sensory and motor latency, amplitude and conduction velocity were recorded in both experimental groups and analyzed using the Student's t-test. RESULTS: SCA7 patients showed a significant prolongation of sensory nerve conduction latencies, as well as a decrease in sensory amplitudes. Decreases in motor amplitudes and peroneal conduction velocity were also observed. Finally, we found an association between CAG repeats and the severity of cerebellar and non-cerebellar symptoms with electrophysiological signs of demyelinization. DISCUSSION: Our results reveal the existence of a critical sensorimotor peripheral neuropathy in SCA7 patients. Moreover, we show that using sensitive electrophysiological tools to evaluate nerve conduction can improve the diagnosis and design of therapeutic options based on pharmacological and rehabilitative strategies. CONCLUSION: These findings demonstrate that SCA7 is a disease that globally affects the peripheral nervous system.
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Enfermedades del Sistema Nervioso Periférico/genética , Ataxias Espinocerebelosas/complicaciones , Adolescente , Adulto , Anciano , Electromiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/fisiopatologíaRESUMEN
The prodromal phase of spinocerebellar ataxias (SCAs) has not been systematically studied. Main findings come from a homogeneous SCA type 2 (SCA2) population living in Cuba. The aim of this study was to characterize extensively the prodromal phase of SCA2 by several approaches. Thirty-seven non-ataxic SCA2 mutation carriers and its age- and sex-matched controls underwent clinical assessments, including standardized neurological exam, structured interviews and clinical scales, and looking for somatic and autonomic features, as well as a neuropsychological battery, antisaccadic recordings, and MRI scans. Main clinical somatic features of non-ataxic mutation carriers were cramps, sensory symptoms, sleep disorders, and hyperreflexia, whereas predominating autonomic symptoms were pollakiuria/nocturia, constipation, and frequent throat clearing. Cognitive impairments included early deficits of executive functions and visual memory, suggesting the involvement of cerebro-cerebellar-cerebral loops and/or reduced cholinergic basal forebrain input to the cortex. Antisaccadic task revealed impaired oculomotor inhibitory control but preserved ability for error correction. Cognitive and antisaccadic deficits were higher as carriers were closer to the estimated onset of ataxia, whereas higher Scale for the Assessment and Rating of Ataxia (SARA) scores were associated most notably to vermis atrophy. The recognition of early features of SCA2 offers novel insights into the prodromal phase and physiopathological base of the disease, allowing the assessment of its progression and the efficacy of treatments, in particular at early phases when therapeutical options should be most effective.
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Ataxias Espinocerebelosas/epidemiología , Ataxias Espinocerebelosas/fisiopatología , Adulto , Anciano , Ataxinas , Encéfalo/patología , Encéfalo/fisiopatología , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Cuba/epidemiología , Medidas del Movimiento Ocular , Femenino , Humanos , Entrevistas como Asunto , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación , Proteínas del Tejido Nervioso/genética , Examen Neurológico , Pruebas Neuropsicológicas , Síntomas Prodrómicos , Movimientos Sacádicos , Índice de Severidad de la Enfermedad , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/patología , Adulto JovenRESUMEN
Spinocerebellar ataxia type 7 (SCA7) is a genetic disorder characterized by degeneration of the cerebellum, brainstem, and retina that is caused by abnormal expansion of a CAG repeat located in the ATXN7 gene encoding sequence on chromosome 3p21.1. Although SCA7 is an uncommon autosomal dominant ataxia, we previously found increased prevalence of the disease in a Southeastern Mexican population. In this study, we described to our knowledge for the first time a marriage of consanguineous SCA7 mutation carriers and their offspring effect. We characterized a severely affected infantile-onset female patient whose parents and two siblings exhibited no symptoms of the disease at time of diagnosis. A comprehensive clinical analysis of the proband showed a progressive cerebellar syndrome, including gait ataxia, movement disorders, and saccadic movements, as well as hyperreflexia, visual deterioration, urinary and cardiovascular dysfunction, and impaired nerve conduction. The SCA7 mutation was detected in the proband patient. Subsequently, genetic examination using four ATXN7 gene-linked markers (three centromeric microsatellite markers [D3S1228, D3S1287, and D3S3635] and an intragenic Single Nucleotide Polymorphism [SNP-3145G/A]) revealed that the proband descends from a couple of consanguineous SCA7 mutation carriers. Genotyping analysis demonstrated that all offspring inherited only one mutant allele, and that the severe infantile-onset phenotype is caused by germinal expansion (from 37 to 72 CAG repeats) of the paternal mutant allele. Interestingly, the couple also referred a miscarriage. Finally, we found no CAA interruptions in the ATXN7 gene CAG repeats tract in this family, which might explain, at least in part, the triplet instability in the proband.
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Histamine H3 receptors (H3Rs) co-localize with dopamine (DA) D1 receptors (D1Rs) on striatal medium spiny neurons and functionally antagonize D1R-mediated responses. The intra-striatal administration of D1R agonists reduces DA release whereas D1R antagonists have the opposite effect. In this work, a microdialysis method was used to study the effect of co-activating D1 and H3 receptors on the release of DA from the rat dorsal striatum. Infusion of the D1R agonist SKF-38393 (0.5 and 1 µM) significantly reduced DA release (26-58%), and this effect was prevented by co-administration of the H3R agonist immepip (10 µM). In turn, the effect of immepip was blocked by the H3R antagonist thioperamide (10 µM). Our results indicate that co-stimulation of post-synaptic D1 and H3 receptors may indirectly regulate basal DA release in the rat striatum and provide in vivo evidence for a functional interaction between D1 and H3 receptors in the basal ganglia.
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Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Antagonistas de los Receptores Histamínicos H3/farmacología , Receptores de Dopamina D1/fisiología , Receptores Histamínicos H3/fisiología , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/administración & dosificación , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/antagonistas & inhibidores , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , Animales , Cuerpo Estriado/efectos de los fármacos , Agonistas de Dopamina/administración & dosificación , Agonistas de Dopamina/farmacología , Interacciones Farmacológicas , Agonistas de los Receptores Histamínicos/administración & dosificación , Agonistas de los Receptores Histamínicos/farmacología , Imidazoles/administración & dosificación , Imidazoles/antagonistas & inhibidores , Imidazoles/farmacología , Masculino , Microdiálisis , Microinyecciones , Piperidinas/administración & dosificación , Piperidinas/antagonistas & inhibidores , Piperidinas/farmacología , Ratas , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiologíaRESUMEN
INTRODUCTION: Acetylcholine is an essential neurotransmitter in the central nervous system as it has an effect on sleep, memory and learning. Intracerebral microdialysis is an in vivo surgical technique that is used to measure the concentration of substances in the extracellular space. METHODS: The rats were stereotaxically implanted with microdialysis cannulae guided to the hypothalamic medial preoptic area and bipolar stainless steel electrodes to obtain sleep records simultaneously with microdialysis samplings during 24 hours exposed to clean air followed by 24 hours of exposure to ozone. Microdialysis fractions were injected into chromatograph system. RESULTS: Results showed that paradoxical sleep and wakefulness decreased by 54.2% and 27.9%, respectively, while slow wave sleep increased by 35.1% during the ozone exposure phase and a concomitant decrease of extracellular acetylcholine of 56.2% was observed during the light-dark phase. CONCLUSION: That surgical method employed using electroencephalography and intracerebral microdialysis allows the quantification of extracellular acetylcholine and simultaneously with patterns related to sleep. We propose that the decrease in paradoxical sleep is the behavioral expression of disruptions of cholinergic modulation and, that post-exposure effects observed in the hypothalamic medial preoptic area can be explained on the basis of the hypothalamic role in the sleep-wake cycle.
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Acetilcolina/análisis , Química Encefálica , Sueño/fisiología , Animales , Electroencefalografía , Masculino , Ratas , Ratas WistarRESUMEN
INTRODUCTION: It has been proposed that noradrenaline is one of the neurotransmitters involved in the functional recovery. In this sense, it has been proposed that the alpha-2 noradrenergic receptors play an important role in the functional reinstatement. OBJECTIVE: the aim of this work was to study the role of the alpha-2 noradrenergic receptors on the noradrenaline contents in cerebellum and pons of rats iron-injured in the motor cortex. METHODS: Fifteen male Wistar rats were allocated in three groups: control (n = 5) with intracortical infusion of saline (0.9%), injured (n = 5) with intracortical infusion of dextran iron and intraventricular infusion of saline, and injured + yohimbine (alpha-2 receptor antagonist; n = 5) that received an intracortical infusion of dextran iron and also an intraventricular infusion of yohimbine. Motor behavior was assessed by means of the beam-walking paradigm. Three days after surgeries, the animals were sacrificed and the left and right sides of the pons and the cerebellar hemispheres were extracted. Tissues were prepared for noradrenaline analysis by means of high performance liquid chromatography. RESULTS: We observed that the yohimbine-treated animals had a noradrenaline increase in the right side of the pons and a decrease in the right cerebellar hemisphere. CONCLUSION: It is concluded that the blockage of the alpha-2 receptors leads to an increase of noradrenaline in the locus coeruleus, which retards the effects of the cerebral injury.
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Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Lesiones Encefálicas/fisiopatología , Corteza Motora/efectos de los fármacos , Corteza Motora/fisiopatología , Desempeño Psicomotor/efectos de los fármacos , Receptores Adrenérgicos/efectos de los fármacos , Yohimbina/farmacología , Antagonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Animales , Infusiones Intraventriculares , Masculino , Ratas , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Yohimbina/administración & dosificaciónRESUMEN
Toluene, found in glues and cleaners, is among the inhalants most commonly abused by workers and young drug addicts. In this study, we examined the changes in sleep patterns and monoamine content induced by chronic toluene exposure. Rats were chronically exposed to toluene vapors beginning at 30 days of age for a duration of 30 days. Experiment I was performed in a control group (n=10) and a chronic toluene exposure group (n=10). Rats were implanted with bipolar stainless steel electrodes for electroencephalographic recording (EEG). In experiment II, conducted in two other groups (control and exposed to toluene, n=10 each), animals were sacrificed by decapitation prior to chromatographic analysis. We found that chronic toluene administration affected the organization of sleep patterns and monoamine content. Dopamine (DA) and noradrenaline (NA) increased in the midbrain and striatum. 3,4-dihydroxyphenylacetic acid (DOPAC) increased only in the striatum. Midbrain levels of serotonin (5-HT) increased in the pons and decreased in the hypothalamus and striatum. 5-hydroxyindoleacetic acid (5-HIAA) increased in the pons, midbrain and striatum and decreased in the hypothalamus. Chronic toluene exposure induced changes in the serotonergic and dopaminergic systems and increased SWS and PS deficits. We conclude that toluene exposure disrupts the sleep-wake cycle by affecting the monoaminergic response in cerebral areas related to sleep.
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Monoaminas Biogénicas/metabolismo , Encéfalo/efectos de los fármacos , Sueño/efectos de los fármacos , Solventes/farmacología , Tolueno/farmacología , Vigilia/efectos de los fármacos , Análisis de Varianza , Animales , Encéfalo/metabolismo , Ondas Encefálicas/efectos de los fármacos , Cromatografía Líquida de Alta Presión/métodos , Electroencefalografía , Electromiografía , Masculino , Ratas , Ratas WistarRESUMEN
The aim of this work was to analyze the effect of oxcarbazepine (OXC) on sleep patterns, "head and body shakes" and monoamine neurotransmitters level in a model of kainic-induced seizures. Adult Wistar rats were administered kainic acid (KA), OXC or OXC + KA. A polysomnographic study showed that KA induced animals to stay awake for the whole initial 10 h. OXC administration 30 min prior to KA diminished the effect of KA on the sleep parameters. As a measure of the effects of the drug treatments on behavior, head and body shakes were visually recorded for 4 h after administration of KA, OXC + KA or saline. The presence of OXC diminished the shakes frequency. 4 h after drug application, the hippocampus was dissected out, and the content of monoamines was analyzed. The presence of OXC still more increased serotonin, 5-hidroxyindole acetic acid, dopamine, and homovanilic acid, induced by KA.
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Carbamazepina/análogos & derivados , Dopamina/metabolismo , Hipocampo/efectos de los fármacos , Convulsiones/tratamiento farmacológico , Serotonina/metabolismo , Fases del Sueño/efectos de los fármacos , Animales , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéutico , Carbamazepina/administración & dosificación , Carbamazepina/uso terapéutico , Modelos Animales de Enfermedad , Ácido Homovanílico/metabolismo , Ácido Hidroxiindolacético/metabolismo , Ácido Kaínico/efectos adversos , Masculino , Oxcarbazepina , Ratas , Ratas Wistar , Convulsiones/inducido químicamenteRESUMEN
The sensorimotor cortex and the cerebellum are interconnected by the corticopontocerebellar (CPC) pathway and by neuronal groups such as the serotonergic system. Our aims were to determine the levels of cerebellar serotonin (5-HT) and lipid peroxidation (LP) after cortical iron injection and to analyze the motor function produced by the injury. Rats were divided into the following three groups: control, injured and recovering. Motor function was evaluated using the beam-walking test as an assessment of overall locomotor function and the footprint test as an assessment of gait. We also determined the levels of 5-HT and LP two and twenty days post-lesion. We found an increase in cerebellar 5-HT and a concomitant increase in LP in the pons and cerebellum of injured rats, which correlated with their motor deficits. Recovering rats showed normal 5-HT and LP levels. The increase of 5-HT in injured rats could be a result of serotonergic axonal injury after cortical iron injection. The LP and motor deficits could be due to impairments in neuronal connectivity affecting the corticospinal and CPC tracts and dysmetric stride could be indicative of an ataxic gait that involves the cerebellum.
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Cerebelo/metabolismo , Marcha , Peroxidación de Lípido , Actividad Motora , Degeneración Nerviosa/metabolismo , Puente/metabolismo , Serotonina/metabolismo , Animales , Compuestos Ferrosos , Masculino , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/fisiopatología , Degeneración Nerviosa/psicología , Ratas , Ratas WistarRESUMEN
Iron chloride injections into the rat SNc can cause chronic decreases in striatal dopamine (DA) levels. However, changes in striatal DA content after iron-dextran injection into rat SNc have not been completely elucidated. The aim of this work was to measure striatal DA concentrations after iron-dextran injection into the SNc. We divided 40 male Wistar rats into five groups, including control, saline injected then sacrificed 7 days or 30 days later, and iron-dextran injected then sacrificed 7 days or 30 days later. Striatal DA content was measured in control animals and in all animals sacrificed 7 days or 30 days after injection, and motor performance was assessed in iron-dextran and saline injected groups 30 days after injection. The striatal DA levels were determined using HPLC. There were significant (P < 0.05) decreases in DA concentrations in the striatum ipsilateral to the injection site in the iron-dextran treated rats compared to control and saline-injected rats. There were no significant differences in DA concentration between the sham-operated (i.e., saline-injected) and control rats. We also observed motor deficits in the iron-dextran injected rats. The striatal DA reduction observed after iron-dextran injection may be attributable to iron-induced oxidative injury in the SNc. Motor deficits, in turn, may be explained by subsequent disturbances in striatal and cortical dopaminergic neuromodulation.