RESUMEN
Sleep disturbances and persistent pain conditions are public health challenges worldwide. Although it is well-known that sleep deficit increases pain sensitivity, the underlying mechanisms remain elusive. We have recently demonstrated the involvement of nucleus accumbens (NAc) and anterior cingulate cortex (ACC) in the pronociceptive effect of sleep restriction. In this study, we found that sleep restriction increases c-Fos expression in NAc and ACC, suggesting hyperactivation of these regions during prolonged wakefulness in male Wistar rats. Blocking adenosine A2A receptors in the NAc or GABAA receptors in the ventral tegmental area (VTA), dorsal raphe nucleus (DRN), or locus coeruleus (LC) effectively mitigated the pronociceptive effect of sleep restriction. In contrast, the blockade of GABAA receptors in each of these nuclei only transiently reduced carrageenan-induced hyperalgesia. Pharmacological activation of dopamine D2, serotonin 5-HT1A and noradrenaline alpha-2 receptors within the ACC also prevented the pronociceptive effect of sleep restriction. While pharmacological inhibition of these same monoaminergic receptors in the ACC restored the pronociceptive effect which had been prevented by the GABAergic disinhibition of the of the VTA, DRN or LC. Overall, these findings suggest that the pronociceptive effect of sleep restriction relies on increased adenosinergic activity on NAc, heightened GABAergic activity in VTA, DRN, and LC, and reduced inhibitory monoaminergic activity on ACC. These findings advance our understanding of the interplay between sleep and pain, shedding light on potential NAc-brainstem-ACC mechanisms that could mediate increased pain sensitivity under conditions of sleep impairment.
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Núcleo Accumbens , Ratas Wistar , Privación de Sueño , Área Tegmental Ventral , Animales , Masculino , Privación de Sueño/metabolismo , Privación de Sueño/fisiopatología , Ratas , Área Tegmental Ventral/metabolismo , Área Tegmental Ventral/efectos de los fármacos , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efectos de los fármacos , Receptor de Adenosina A2A/metabolismo , Hiperalgesia/metabolismo , Núcleo Dorsal del Rafe/metabolismo , Núcleo Dorsal del Rafe/efectos de los fármacos , Giro del Cíngulo/metabolismo , Giro del Cíngulo/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Tronco Encefálico/metabolismo , Tronco Encefálico/efectos de los fármacos , Locus Coeruleus/metabolismo , Locus Coeruleus/efectos de los fármacos , Carragenina , Receptores de GABA-A/metabolismo , Receptores de Dopamina D2/metabolismo , Antagonistas del Receptor de Adenosina A2/farmacologíaRESUMEN
OSA is known to increase the risk for SUDEP in persons with epilepsy, but the relationship between these two factors is not clear. Also, there is no study showing the acute responses to obstructive apnea in a chronic epilepsy model. Therefore, this study aimed to characterize cardiorespiratory responses to obstructive apnea and chemoreceptor stimulation in rats. In addition, we analyzed respiratory centers in the brain stem by immunohistochemistry. Epilepsy was induced with pilocarpine. About 30-60 days after the first spontaneous seizure, tracheal and thoracic balloons, and electrodes for recording the electroencephalogram, electromyogram, and electrocardiogram were implanted. Intermittent apneas were made by inflation of the tracheal balloon during wakefulness, NREM sleep, and REM sleep. During apnea, respiratory effort increased, and heart rate fell, especially with apneas made during wakefulness, both in control rats and rats with epilepsy. Latency to awake from apnea was longer with apneas made during REM than NREM, but rats with epilepsy awoke more rapidly than controls with apneas made during REM sleep. Rats with epilepsy also had less REM sleep. Cardiorespiratory responses to stimulation of carotid chemoreceptors with cyanide were similar in rats with epilepsy and controls. Immunohistochemical analysis of Phox2b, tryptophan hydroxylase, and NK1 in brain stem nuclei involved in breathing and sleep (retrotrapezoid nucleus, pre-Bötzinger complex, Bötzinger complex, and caudal raphe nuclei) revealed no differences between control rats and rats with epilepsy. In conclusion, our study showed that rats with epilepsy had a decrease in the latency to awaken from apneas during REM sleep, which may be related to neuroplasticity in some other brain regions related to respiratory control, awakening mechanisms, and autonomic modulation.
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Modelos Animales de Enfermedad , Electroencefalografía , Epilepsia , Apnea Obstructiva del Sueño , Vigilia , Animales , Vigilia/fisiología , Masculino , Epilepsia/fisiopatología , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/complicaciones , Ratas , Enfermedad Crónica , Pilocarpina/toxicidad , Tronco Encefálico/fisiopatología , Frecuencia Cardíaca/fisiología , Electromiografía , Ratas Sprague-Dawley , Ratas WistarRESUMEN
OBJECTIVE: The lateral aspect of the cerebellomesencephalic fissure frequently harbors vascular pathology and is a common surgical corridor used to access the pons tegmentum, as well as the cerebellum and its superior and middle peduncles. The quadrangular lobule of the cerebellum (QLC) represents an obstacle to reach these structures. The authors sought to analyze and compare exposure of the cerebellar interpeduncular region (CIPR) before and after QLC resection and provide a case series to evaluate its clinical applicability. METHODS: Forty-two sides of human brainstems were prepared with Klingler's method and dissected. The exposure area before and after resection of the QLC was measured and statistically studied. A case series of 59 patients who underwent QLC resection for the treatment of CIPR lesions was presented and clinical outcomes were evaluated at 1-year follow-up. RESULTS: The anteroposterior surgical corridor of the CIPR increased by 10.3 mm after resection of the QLC. The mean exposure areas were 42 mm2 before resection of the QLC and 159.6 mm2 after resection. In this series, ataxia, extrapyramidal syndrome, and akinetic mutism were found after surgery. However, all these cases resolved within 1 year of follow-up. Modified Rankin Scale score improved by 1 grade, on average. CONCLUSIONS: QLC resection significantly increased the exposure area, mainly in the anteroposterior axis. This surgical strategy appears to be safe and may help the neurosurgeon when operating on the lateral aspect of the cerebellomesencephalic fissure.
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Cerebelo , Procedimientos Neuroquirúrgicos , Humanos , Cerebelo/cirugía , Procedimientos Neuroquirúrgicos/métodos , Tronco Encefálico/cirugía , Microcirugia/métodos , Craneotomía/métodosRESUMEN
AIMS: Very Low Birthweight (VLBW) infants with neonatal Chronic Lung Disease (CLD) have been found to have functional impairment of the brainstem auditory pathway at term. This study investigated the functional status of the brainstem auditory pathway in VLBW infants with CLD after term for any abnormality. METHODS: Fifty-two VLBW infants were recruited at 50 weeks of Postconceptional Age: 25 with neonatal CLD and 27 without CLD. None had any other major complications to minimize confounding effects. Brainstem Auditory Evoked Responses were studied at 21â91/s click rates. RESULTS: Compared with those without CLD, VLBW infants with CLD had relatively shorter latencies of BAER waves I and III, associated with a slightly lower BAER threshold. Wave V latency and IâV interpeak interval did not differ significantly between the two groups of infants. The IâIII interval in infants with CLD was shorter than in those without CLD at 91/s clicks. However, the IIIâV interval was significantly longer than in those without CLD at all click rates (all p < 0.05). There were no significant differences in the amplitudes of BAER wave components between the two groups of infants. CONCLUSIONS: The main BAER abnormality in VLBW infants with CLD was a prolonged IIIâV interval. Auditory conduction is delayed or impaired at more central regions of the brainstem in CLD infants. After term central auditory function is adversely affected by neonatal CLD. Monitoring post-term change is required to provide valuable information for post-term care of CLD infants.
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Enfermedades Pulmonares , Recién Nacido , Lactante , Humanos , Adulto , Enfermedades Pulmonares/complicaciones , Audición , Vías Auditivas , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Tronco EncefálicoAsunto(s)
Tronco Encefálico , Cerebelo , Leucoencefalopatía Multifocal Progresiva , Humanos , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/patología , Leucoencefalopatía Multifocal Progresiva/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Masculino , Imagen por Resonancia Magnética , Persona de Mediana Edad , FemeninoRESUMEN
Cerebellar ataxia is a heterogeneous group of neural disorders clinically characterized by cerebellar dysfunction. The diagnosis of patients with progressive cerebellar ataxia is complex due to the direct correlation with other neuron diseases. Although there is still no cure for this pathological condition, some metabolic, hereditary, inflammatory, and immunological factors affecting cerebellar ataxia are being studied and may become therapeutic targets. Advances in studying the neuroanatomy, pathophysiology, and molecular biology of the cerebellum (CE) contribute to a better understanding of the mechanisms behind the development of this disorder. In this study, Wistar rats aged 30 to 35 days were injected intraperitoneally with 3-acetylpyridine (3-AP) and/or metformin (for AMP-activated protein kinase (AMPK) enzyme activation) and euthanized in 24 hours and 4 days after injection. We analyzed the neuromodulatory role of the AMPK on cerebellar ataxia induced by the neurotoxin 3-AP in the brain stem (BS) and CE, after pre-treatment for 7 and 15 days with metformin, a pharmacological indirect activator of AMPK. The results shown here suggest that AMPK activation in the BS and CE leads to a significant reduction in neuroinflammation in these regions. AMPK was able to restore the changes in fatty acid composition and pro-inflammatory cytokines caused by 3-AP, suggesting that the action of AMPK seems to result in a possible neuroprotection on the cerebellar ataxia model.
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Proteínas Quinasas Activadas por AMP , Ataxia Cerebelosa , Modelos Animales de Enfermedad , Metformina , Fármacos Neuroprotectores , Ratas Wistar , Metformina/farmacología , Metformina/uso terapéutico , Animales , Ataxia Cerebelosa/tratamiento farmacológico , Ataxia Cerebelosa/metabolismo , Ataxia Cerebelosa/patología , Proteínas Quinasas Activadas por AMP/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Masculino , Neurotoxinas/toxicidad , Activación Enzimática/efectos de los fármacos , Ratas , Cerebelo/efectos de los fármacos , Cerebelo/patología , Cerebelo/metabolismo , Tronco Encefálico/efectos de los fármacos , Tronco Encefálico/metabolismo , Tronco Encefálico/patología , Citocinas/metabolismo , PiridinasRESUMEN
Maternal protein malnutrition during developmental periods might impair the redox state and the brain's excitatory/inhibitory neural network, increasing central sympathetic tone. Conversely, moderate physical exercise at an early age reduces the risk of chronic diseases. Thus, we hypothesized that a moderate training protocol could reduce the harmful effects of a low-protein maternal diet on the brainstem of young male offspring. We used a rat model of maternal protein restriction during the gestational and lactation period followed by an offspring's continuous treadmill exercise. Pregnant rats were divided into two groups according to the protein content in the diet: normoprotein (NP), receiving 17% of casein, and low protein (LP), receiving 8% of casein until the end of lactation. At 30 days of age, the male offspring were further subdivided into sedentary (NP-Sed and LP-Sed) or exercised (NP-Ex and LP-Ex) groups. Treadmill exercise was performed as follows: 4 weeks, 5 days/week, 60 min/day at 50% of maximal running capacity. The trained animals performed a treadmill exercise at 50% of the maximal running capacity, 60 min/day, 5 days/week, for 4 weeks. Our results indicate that a low-protein diet promotes deficits in the antioxidant system and a likely mitochondrial uncoupling. On the other hand, physical exercise restores the redox balance, which leads to decreased oxidative stress caused by the diet. In addition, it also promotes benefits to GABAergic inhibitory signaling. We conclude that regular moderate physical exercise performed in youthhood protects the brainstem against changes induced by maternal protein restriction.
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Tronco Encefálico , Caseínas , Embarazo , Femenino , Ratas , Animales , Masculino , Humanos , Ratas Wistar , Tronco Encefálico/metabolismo , Antioxidantes/metabolismo , Oxidación-Reducción , Dieta con Restricción de Proteínas/efectos adversos , Fenómenos Fisiologicos Nutricionales MaternosRESUMEN
Introducción: La alucinosis peduncular (AP) hace referencia a alucinaciones autodiscriminadas, cuyo origen son lesiones en el mesencéfalo y en el puente. Presentación del caso: Paciente 27 años, femenina, con alucinaciones visuales, auditivas autodiscriminadas por ella misma, sin antecedentes previos de importancia y con lesiones en resonancia magnética cerebral y cervical en el pedúnculo cerebeloso superior, tegmento pontino, y en columna cervical con bandas oligoclonales patrón 2, que cumplían criterios de Mc Donalds para esclerosis múltiple. Discusión: La alucinosis peduncular hace referencia a la presencia de alucinaciones visuales, criticadas por el paciente, con la consecuencia de lesiones de las vías inhibitorias por deaferentación y desinhibición mesencéfalotalámicas, y retinogenículo calcarina, descritas como manifestación de múltiples patologías neurológicas como trauma, afectación vascular, tumores y pocos casos de enfermedad desmielinizante, entre otras. Conclusión: La alucinosis peduncular es una forma atípica de presentación de lesiones pontomesencefálicas descritas en varias patologías; se debe tener en cuenta en la localización de la lesión neurológica; se han reportado pocos casos como síntoma de la enfermedad desmielinizante.
Introduction: Peduncular hallucinosis (PA) refers to self-discriminating hallucinations, these are caused by lesions in the midbrain and pons. Presentation of the case: 27-year-old right handed female patient with visual and auditory hallucinations self-discriminated by the patient, with no prior history of importance and with lesions in cerebral and cervical Magnetic Resonance in the superior cerebellar peduncle, pontine tegmentum, and in the cervical spine with pattern 2 oligo clonal bands, which met Mc Donald's criteria for multiple sclerosis. Discussion: Peduncular hallucinosis refers to the presence of visual hallucinations criticized by the patient, consequence of lesions in the inhibitory pathways with deafferentation and disinhibition of the midbrain-thalamic and retinogeniculus-calcarine pathways. Described as a manifestation of multiple neurological pathologies such as trauma, vascular, tumor and few cases of demyelinating among others. Conclusion: Peduncular hallucinosis is an atypical form of presentation of pontomesencephalic lesions described in several pathologies, it must be taken into account when locating the neurological lesion, few cases have been reported as symptom of the demyelinating disease.
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Enfermedades Desmielinizantes , Diencéfalo , Esclerosis Múltiple , Percepción Visual , Tronco EncefálicoRESUMEN
PURPOSE: The study aimed to summarize all published cases of intrinsic brainstem epidermoid cysts in a timeline to highlight the specific characteristics and individualize the disease, in addition to discussing the best treatment used. METHODS: The scientific literature on pediatric cases of intrinsic epidermoid cysts of the brainstem was analyzed. We present the case of a 1.5-year-old male with incidental presentation, who was treated with gross total resection. We summarize all previously published cases to individualize the disease. RESULTS: We identified 21 patients, including 10 boys and 11 girls, with a mean age of 4.85 (1-15) years at the time of surgery. The most frequent symptoms were cranial nerve palsy (71.4%), pyramidal tract deficit (57.14%), and headache (52.38%). Among the affected cranial nerves, VII was the most frequently reported in 10 patients. CONCLUSION: Brainstem epidermoid cysts are extremely rare pathologies with relevant age involvement in young children. The treatment objective should be the maximum resection of the lesion through a careful approach and with the appropriate tools for the functional preservation of the patient.
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Quiste Epidérmico , Masculino , Femenino , Humanos , Niño , Preescolar , Lactante , Quiste Epidérmico/diagnóstico por imagen , Quiste Epidérmico/cirugía , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/cirugía , Tronco Encefálico/patología , Nervios CranealesRESUMEN
Introducción: Los tumores difusos de tronco representan aproximadamente el 10% de los tumores pediátricos de SNC. Dentro de este grupo se encuentran los gliomas difusos de línea media H3K27M, los cuales presentan mal pronóstico, con una media de supervivencia de entre 9 a 15 meses. La búsqueda de marcadores moleculares es una gran herramienta oncológica al momento de desarrollar nuevas terapéuticas para estos pacientes. Es por esto que la biopsia quirúrgica representa, hoy en día, un eslabón fundamental. Objetivos: El objetivo de este artículo es comunicar, mediante la presentación de dos casos clínicos, el manejo de los tumores difusos de tronco pediátricos mediante su biopsia quirúrgica a cielo abierto por abordaje subtemporal. Descripción de casos: Se presentan dos casos de pacientes pediátricos a quienes se les realizó una biopsia de tronco mediante abordaje subtemporal en el año 2022 en el servicio de neurocirugía pediátrica de la Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (Fleni). El resultado de la anatomía patológica en ambos pacientes resultó de glioma difuso de línea media H3K27M. Se realiza además una revisión de la técnica quirúrgica del abordaje subtemporal. Intervención: Ambos pacientes evolucionaron sin complicaciones en el postoperatorio y mantuvieron seguimiento y tratamiento dirigido por oncología. Aun cuando la práctica más utilizada es la biopsia estereotáctica, nosotros preferimos la vía subtemporal a cielo abierto. La misma ha probado resultar efectiva para la obtención de suficiente material tumoral para realizar marcadores oncológicos, con buen control de hemostasia, sin mayores comorbilidades ni demoras en el inicio del tratamiento. Conclusión: Los tumores difusos de tronco pediátricos presentan un pronóstico ominoso, aún realizando tratamiento oncológico dirigido. La biopsia quirúrgica resulta fundamental a fin de obtener un mayor entendimiento respecto a la gran diversidad biológica que subyace a estas entidades y sus opciones terapéuticas, tanto actuales como futuras. El abordaje subtemporal es una excelente vía para realizar su biopsia(AU)
Background: Brainstem diffuse tumors represent approximately 10% of pediatric CNS tumors. Among them, H3K27M-mutant diffuse midline gliomas (DMGs) are rare childhood central nervous system tumors that carry a dismal prognosis, with a mean survival time of 9-15 months. Tumor biopsy is not only helpful for addressing a correct diagnosis, but is also an important strategy for the continuous study of further therapeutic options, given the former known bad prognosis with standard treatment. Objective: Our objective is to communicate, through the presentation of two clinical cases, our experience with these tumors by performing a biopsy through a subtemporal approach. Cases description: Two patients underwent tumor biopsy through a subtemporal approach at our institution in 2022. Both patients presented with MRIs compatible with diffuse pons gliomas. These cases were retrospectively reviewed and the surgical approach described.We also review and compare the different surgical approaches as well as treatment options for this pathology. Surgery: The patients presented no postoperative complication. Both patient's biopsy results were H3K27M-mutant diffuse midline gliomas and underwent oncological treatment and follow up. Although stereotactic biopsy is the most commonly used practice, at our institution we choose to use open surgery through a subtemporal approach. It has proven to provide a better surgical view with a chance of greater biopsy samples, satisfactory bleeding control with no added comorbidities. Nowadays, biopsy has proven fundamental for the treatment and follow up of these patients. Conclusion: DMGs are rare childhood central nervous system tumors that carry a dismal prognosis. Historically, biopsy for brainstem diffuse tumors was used only when the diagnosis was not clear. Nowadays, with the forthcoming of different surgical techniques and the development of new subtypes of molecular targets, the biopsy seems a fundamental step. The subtemporal approach is an excellent alternative to biopsy this pathology(AU)
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Neoplasias del Sistema Nervioso Central , Tronco Encefálico , Sistema Nervioso Central , Oncología Médica , Neoplasias , NeurocirugiaRESUMEN
Parkinson's Disease (PD), treated with the dopamine precursor l-3,4-dihydroxyphenylalanine (L-DOPA), displays motor and non-motor orofacial manifestations. We investigated the pathophysiologic mechanisms of the lateral pterygoid muscles (LPMs) and the trigeminal system related to PD-induced orofacial manifestations. A PD rat model was produced by unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. Abnormal involuntary movements (dyskinesia) and nociceptive responses were determined. We analyzed the immunodetection of Fos-B and microglia/astrocytes in trigeminal and facial nuclei and morphological markers in the LPMs. Hyperalgesia response was increased in hemiparkinsonian and dyskinetic rats. Hemiparkinsonism increased slow skeletal myosin fibers in the LPMs, while in the dyskinetic ones, these fibers decreased in the contralateral side of the lesion. Bilateral increased glycolytic metabolism and an inflammatory muscle profile were detected in dyskinetic rats. There was increased Fos-B expression in the spinal nucleus of lesioned rats and in the motor and facial nucleus in L-DOPA-induced dyskinetic rats in the contralateral side of the lesion. Glial cells were increased in the facial nucleus on the contralateral side of the lesion. Overall, spinal trigeminal nucleus activation may be associated with orofacial sensorial impairment in Parkinsonian rats, while a fatigue profile on LPMs is suggested in L-DOPA-induced dyskinesia when the motor and facial nucleus are activated.
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Discinesia Inducida por Medicamentos , Enfermedad de Parkinson , Trastornos Parkinsonianos , Ratas , Animales , Levodopa/farmacología , Discinesia Inducida por Medicamentos/metabolismo , Cuerpo Estriado/metabolismo , Trastornos Parkinsonianos/metabolismo , Enfermedad de Parkinson/metabolismo , Oxidopamina/efectos adversos , Tronco Encefálico/metabolismo , Modelos Animales de Enfermedad , Antiparkinsonianos/efectos adversosRESUMEN
Leukodystrophies are a group of genetic diseases with diverse clinical features and prominent involvement of the central nervous system white matter. We describe a 27-year-old man who presented with a progressive neurological disease, and striking involvement of the brainstem and symmetrical white matter lesions on MR scanning. Having excluded several other causes of leukodystrophy, we confirmed Alexander disease when a genetic panel showed a probable pathogenic variant in GFAP: p.Leu359Pro. Clinicians should suspect Alexander disease in people with a progressive neurological motor decline who has pyramidal and bulbar signs and compatible neuroimaging.
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Enfermedad de Alexander , Médula Cervical , Masculino , Humanos , Adulto , Enfermedad de Alexander/complicaciones , Enfermedad de Alexander/diagnóstico por imagen , Enfermedad de Alexander/genética , Proteína Ácida Fibrilar de la Glía/genética , Médula Cervical/patología , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/patología , Imagen por Resonancia Magnética/métodosRESUMEN
El cerebelo ocupa la fosa posterior (foto 15-1), por debajo del tentorio, y por delante del tronco cerebral al cual está unido sólo por tres estructuras , llamadas pedúnculos cerebelosos. El cerebelo, sólo representa un 10% del peso del encéfalo, pero contiene la mitad de las neuronas del mismo.
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Cerebelo , Encéfalo , Tronco Encefálico , Duramadre , NeuronasRESUMEN
The dorsal cochlear nucleus (DCN) in the auditory brainstem integrates auditory and somatosensory information. Mature DCN fusiform neurons fall into two qualitatively distinct types: quiet, with no spontaneous regular action potential firing, or active, with regular spontaneous action potential firing. However, how these firing states and other electrophysiological properties of fusiform neurons develop during early postnatal days to adulthood is not known. Thus, we recorded fusiform neurons from mice from P4 to P21 and analyzed their electrophysiological properties. In the prehearing phase (P4-P13), we found that most fusiform neurons are quiet, with active neurons emerging after hearing onset at P14. Subthreshold properties underwent significant changes before hearing onset, whereas changes to the action potential waveform occurred mainly after P14, with the depolarization and repolarization phases becoming markedly faster and half-width significantly decreased. The activity threshold in posthearing neurons was more negative than in prehearing cells. Persistent sodium current (INaP) was increased after P14, coinciding with the emergence of spontaneous firing. Thus, we suggest that posthearing expression of INaP leads to hyperpolarization of the activity threshold and the active state of the fusiform neuron. At the same time, other changes refine the passive membrane properties and increase the speed of action potential firing of fusiform neurons.NEW & NOTEWORTHY Auditory brainstem neurons express unique electrophysiological properties adapted for their complex physiological functions that develop before hearing onset. Fusiform neurons of the DCN present two firing states, quiet and active, but the origin of these states is not known. Here, we showed that the quiet and active states develop after hearing onset at P14, along with changes in action potentials, suggesting an influence of auditory input on the refining of fusiform neuron's excitability.
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Núcleo Coclear , Animales , Ratones , Audición , Neuronas , Potenciales de Acción , Tronco EncefálicoRESUMEN
Poor nutritional quality in the early stages of development is associated with neurological diseases in adulthood. Studies showed that obesity-induced oxidative stress contributes to the genesis of neurological diseases through dysregulation of the brainstem and hypothalamus. Fluoxetine (Fx) is an antidepressant member in the family of selective serotonin reuptake inhibitors (SSRI) that can induce positive effects by reducing oxidative damage in brain tissues. We aimed to evaluate the late effect of Fx in the brainstem and hypothalamus of overnourished rats during development. Male Wistar rats, after birth, were randomly divided into the normal-nourished group (N, n = 9) and the overnourished group (O, n = 3). On the 39th day of life, the groups were subdivided into normofed, and the overnourished group treated or not with fluoxetine (10 mg/kg daily) (NF, NV, OF, and OV). All groups were treated from the 39th to the 59th day of life, and within 90 days, the tissues were collected for oxidative stress analysis. Briefly, our results showed that Fx treatment induced a tissue-dependent long-lasting effect in overfed animals, increasing the enzymatic defense (i.e., CAT and GST activity) in the hypothalamus, but more intensive, increasing the non-enzymatic defense (i.e., Total Thiols and GSH levels) in the brainstem. Overall, our study suggests that serotonin modulation at the final stage of brain development causes a long-lasting impact on brain structures in overfed rats at a different mode.
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Fluoxetina , Estrés Oxidativo , Ratas , Animales , Masculino , Fluoxetina/farmacología , Ratas Wistar , Hipotálamo , Tronco EncefálicoRESUMEN
Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is the most common SCA worldwide and comprises about 70% of SCA patients in Brazil. Magnetic resonance imaging (MRI) sequences have been used to describe microstructural abnormalities in many neurodegenerative diseases and helped to reveal the excessive iron accumulation in many of these conditions. This study aimed to characterize brain changes in gray matter (GM) and white matter (WM), detected by voxel-based morphometry (VBM) and relaxometry in patients with SCA3/MJD. A group of consecutive individuals, older than 18 years of age, with symptomatic and genetically proven SCA3/MJD diagnosed, and a control group, were submitted to clinical evaluation and MRI. The images were analyzed using VBM technique and relaxometry. The global assessment of brain volume by region of interest showed a significant difference in GM between SCA3/MJD and normal controls. VBM was used to locate these volumetric changes and it revealed a noticeable difference in the GM of the cerebellum and the brainstem. The global assessment of the brain by relaxometry also showed a significant difference in the comparison of GM between SCA3/MJD and normal controls, detecting noticeable prolongation of T2 time in the medulla oblongata (p < 0.001) and in the pontine tegmentum (p = 0.009) in SCA3/MJD compared to control group. Our study suggests that SCA3/MJD affects the macrostructure of the cerebellum and brainstem and microstructure of pons and medulla oblongata GM, as already demonstrated in the pathological study.
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Enfermedad de Machado-Joseph , Ataxias Espinocerebelosas , Humanos , Enfermedad de Machado-Joseph/diagnóstico , Ataxias Espinocerebelosas/diagnóstico , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Tronco EncefálicoRESUMEN
MAIN AIM: To electrophysiologically determine the impact of moderate to severe chronic hypoxia (H) resulting from a wide array of CHD (HCHD) conditions on the integrity of brainstem function. MATERIALS AND METHODS: Applying brainstem auditory-evoked response methodology, 30 chronically afflicted HCHD patients, who already had undergone heart surgery, were compared to 28 healthy control children (1-15 yo) matched by age, gender and socioeconomic condition. Blood oxygen saturation was clinically determined and again immediately before brainstem auditory-evoked response testing. RESULTS: Among HCHD children, auditory wave latencies (I, III and V) were significantly longer (medians: I, 2.02 ms; III, 4.12 ms, and; V, 6.30 ms) compared to control (medians: I, 1.67ms; III, 3.72 ms, and; V, 5.65 ms), as well as interpeak intervals (HCHD medians: I-V, 4.25 ms, and; III-V, 2.25ms; control medians: I-V, 3.90 ms and, III-V, 1.80 ms) without significant differences in wave amplitudes between groups. A statistically significant and inverse correlation between average blood oxygen saturation of each group (control, 94%; HCHD, 78%) and their respective wave latencies and interpeak intervals was found. CONCLUSIONS: As determined by brainstem auditory-evoked responses, young HCHD patients manifestly show severely altered neuronal conductivity in the auditory pathway strongly correlated with their hypoxic condition. These observations are strongly supported by different brainstem neurological and image studies showing that alterations, either in microstructure or function, result from the condition of chronic hypoxia in CHD. The non-altered wave amplitudes are indicative of relatively well-preserved neuronal relay nuclei.