Changes in Noradrenergic Synthesis and Dopamine Beta-Hydroxylase Activity in Response to Oxidative Stress after Iron-induced Brain Injury.

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.

Protocolos de rehabilitación y fisioterapia en pacientes afectados por COVID-19

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.

Alpha2-adrenergic receptor activation reinstates motor deficits in rats recovering from cortical injury.

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.

Glutamate, Glutamine, GABA and Oxidative Products in the Pons Following Cortical Injury and Their Role in Motor Functional Recovery.

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.

Involvement of the Auditory Pathway in Spinocerebellar Ataxia Type 7.

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.

Effects of Physical Rehabilitation in Patients with Spinocerebellar Ataxia Type 7.

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.

Progression of corticospinal tract dysfunction in pre-ataxic spinocerebellar ataxia type 2: A two-years follow-up TMS study.

OBJECTIVE: Corticospinal tract (CST) dysfunction is common in the pre-ataxic stage of spinocerebellar ataxia type 2 (SCA2) but quantitative assessment of its progression over time has not been explored. The aim of this study was to quantify the progression of CST dysfunction in pre-ataxic SCA2 using transcranial magnetic stimulation (TMS). METHODS: Thirty-three pre-ataxic SCA2 mutation carriers and a 33 age- and gender-matched healthy controls were tested at baseline and 2-years follow-up by standardized clinical exams, validated clinical scales, and TMS. RESULTS: Pre-ataxic SCA2 mutation carriers showed a significant increase of resting motor thresholds (RMT) to abductor pollicis brevis (APB) and tibialis anterior (TA) muscles, and of central motor conduction time (CMCT) to TA at 2-years follow-up, over and above changes in healthy controls. The changes in the pre-ataxic SCA2 mutation carriers were independent of the presence of clinical signs of CST dysfunction at baseline, and independent of conversion to clinically definite SCA2 at 2-years follow-up. CONCLUSIONS: TMS markers of CST dysfunction progress significantly during the pre-ataxic stage of SCA2. SIGNIFICANCE: TMS measures of CST dysfunction may provide biomarkers of disease progression prior to clinical disease expression that have potential utility for monitoring neuroprotective therapies in future clinical trials.

Dopamine D1 receptor activation maintains motor coordination in injured rats but does not accelerate the recovery of the motor coordination deficit.

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.

Epidemiología, etiología y clasificación de la enfermedad vascular cerebral / Epidemiology, etiology and classification of stroke

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)

Sensorimotor Intervention Recovers Noradrenaline Content in the Dentate Gyrus of Cortical Injured Rats.

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.