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.
RESUMEN
The brain cortex is the structure that is typically injured in traumatic brain injury (TBI) and is anatomically connected with other brain regions, including the striatum and hypothalamus, which are associated in part with motor function and the regulation of body temperature, respectively. We investigated whether a TBI extending to the striatum could affect peripheral and core temperatures as an indicator of autonomic thermoregulatory function. Moreover, it is unknown whether thermal modulation is accompanied by hypothalamic and cortical monoamine changes in rats with motor function recovery. The animals were allocated into three groups: the sham group (sham), a TBI group with a cortical contusion alone (TBI alone), and a TBI group with an injury extending to the dorsal striatum (TBI + striatal injury). Body temperature and motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, rats were euthanized to measure the serotonin (5-HT), noradrenaline (NA), and dopamine (DA) levels using high-performance liquid chromatography (HPLC). We observed that TBI with an injury extending to the dorsal striatum increased core and peripheral temperatures. These changes were accompanied by a sustained motor deficit lasting for 14 days. Furthermore, there were notable increases in NA and 5-HT levels in the brain cortex and hypothalamus both 3 and 20 days after injury. In contrast, rats with TBI alone showed no changes in peripheral temperatures and achieved motor function recovery by the 7th day post-injury. In conclusion, our results suggest that TBI with an injury extending to the dorsal striatum elevates both core and peripheral temperatures, causing a delay in functional recovery and increasing hypothalamic monoamine levels. The aftereffects can be attributed to the injury site and changes to the autonomic thermoregulatory functions.
RESUMEN
RATIONALE: Dyskinesias induced by L-3,4-dihydroxyphenylalanine, L-Dopa (LIDs), are the major complication in the pharmacological treatment of Parkinson's disease. LIDs induce overactivity of the glutamatergic cortico-striatal projections, and drugs that reduce glutamatergic overactivity exert antidyskinetic actions. Chronic administration of immepip, agonist at histamine H3 receptors (H3R), reduces LIDs and diminishes GABA and glutamate content in striatal dialysates (Avila-Luna et al., Psychopharmacology 236: 1937-1948, 2019). OBJECTIVES AND METHODS: In rats unilaterally lesioned with 6-hydroxydopamine in the substantia nigra pars compacta (SNc), we examined whether the chronic administration of immepip and their withdrawal modify LIDs, the effect of L-Dopa on glutamate and GABA content, and mRNA levels of dopamine D1 receptors (D1Rs) and H3Rs in the cerebral cortex and striatum. RESULTS: The administration of L-Dopa for 21 days induced LIDs. This effect was accompanied by increased GABA and glutamate levels in the cerebral cortex ipsi and contralateral to the lesioned SNc, and immepip administration prevented (GABA) or reduced (glutamate) these actions. In the striatum, GABA content increased in the ipsilateral nucleus, an effect prevented by immepip. L-Dopa administration had no significant effects on striatal glutamate levels. In lesioned and L-Dopa-treated animals, D1R mRNA decreased in the ipsilateral striatum, an effect prevented by immepip administration. CONCLUSIONS: Our results indicate that chronic H3R activation reduces LIDs and the overactivity of glutamatergic cortico-striatal projections, providing further evidence for an interaction between D1Rs and H3Rs in the cortex and striatum under normal and pathological conditions.
Asunto(s)
Discinesia Inducida por Medicamentos , Levodopa , Ratas , Masculino , Animales , Levodopa/efectos adversos , Dopamina/metabolismo , Oxidopamina/toxicidad , Ácido Glutámico/metabolismo , Cuerpo Estriado , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Discinesia Inducida por Medicamentos/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Corteza Cerebral/metabolismo , ARN Mensajero/metabolismoRESUMEN
The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19. The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms. A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a. The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood-nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.
Asunto(s)
COVID-19 , Dolor Crónico , MicroARNs , Síndrome Post Agudo de COVID-19 , Humanos , Dolor Crónico/genética , COVID-19/complicaciones , COVID-19/genética , MicroARNs/genética , Síndrome Post Agudo de COVID-19/genéticaRESUMEN
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.
Asunto(s)
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
Disabilities are estimated to occur in approximately 2% of survivors of traumatic brain injury (TBI) worldwide, and disability may persist even decades after brain injury. Facilitation or modulation of functional recovery is an important goal of rehabilitation in all patients who survive severe TBI. However, this recovery tends to vary among patients because it is affected by the biological and physical characteristics of the patients; the types, doses, and application regimens of the drugs used; and clinical indications. In clinical practice, diverse dopaminergic drugs with various dosing and application procedures are used for TBI. Previous studies have shown that dopamine (DA) neurotransmission is disrupted following moderate to severe TBI and have reported beneficial effects of drugs that affect the dopaminergic system. However, the mechanisms of action of dopaminergic drugs have not been completely clarified, partly because dopaminergic receptor activation can lead to restoration of the pathway of the corticobasal ganglia after injury in brain structures with high densities of these receptors. This review aims to provide an overview of the functionality of the dopaminergic system in the striatum and its roles in functional recovery or rehabilitation after TBI.
RESUMEN
AIM: The purpose of this work was to identify and measure catecholamines, their metabolites, and the gene expression of catecholamine receptors in osteosarcoma tissue. MATERIALS AND METHODS: The levels of 3,4-dihydroxyphenylacetic acid, norepinephrine, serotonin, and 5-hydroxyindoleacetic acid in cancer tissue and in adjacent and non-oncological bone tissue were analysed by high-performance liquid chromatography, and the gene expression of catecholamine receptors and of dopamine ß-hydroxylase, monoaminoxidase, ki67, and Runx2 in the osteosarcoma tissue, tissue adjacent to the tumour, non-oncological bone, and human brain tissue was analysed by RT-PCR. RESULTS: We found significantly higher levels of 3,4-dihydroxyphenylacetic acid and norepinephrine in the cancer sample than in adjacent and non-oncological bone. We found that ß-adrenergic receptors and dopaminergic receptors, dopamine ß-hydroxylase, ki67, Runx2, and serotonergic receptor gene expression were significantly higher in tumour tissue than in adjacent and non-oncological bone. CONCLUSION: Catecholamines and their receptors could be potential molecular markers for osteosarcoma progression.
Asunto(s)
Neoplasias Óseas/patología , Catecolaminas/metabolismo , Regulación de la Expresión Génica , Metaboloma , Osteosarcoma/patología , Receptores de Catecolaminas/metabolismo , Anciano , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteosarcoma/genética , Osteosarcoma/metabolismo , Receptores de Catecolaminas/genéticaRESUMEN
Abstract Introduction Systemic administration of pentylenetetrazole (PTZ) causes brain damage (BD), and triggers a series of morphological and neurochemical changes, which in turn bring about behavioral, cognitive, and motor deficits. Serotonin (5-HT), dopamine (DA), and noradrenaline (NA) levels are controlled by various brain structures and these levels are related to motor activity; however, the concentration of these neurotransmitters during the postictal process remains unknown. Objective We investigated the concentration of 5-HT, NA and DA in the hippocampus, cerebellum, and cortex on motor deficit during the postictal stage. Method Eighteen male Wistar rats (300 g) assigned to two groups: control (n = 9, saline solution) and experimental (n = 9, PTZ) were used. Myoclonic shakes were counted and motor behavior assessments were recorded during three hours post PTZ injection (90 mg/kg). The cortex, cerebellum, and hippocampus of each rat were dissected to determine the 5-HT, DA, and NA concentration by high performance liquid chromatography. Results PTZ induced a significant increase in total 5-HT and DA levels in the hippocampus and cortex; in the cerebellum there was a significant increase in the concentration of 5-HT and NA. The presence of myoclonic shakes as well as a marked motor deficit in the experimental group were significantly different in comparison to the control. Discussion and conclusion 5-HT modifies the concentration of other monoamines directly involved in motor aspects such as NA and DA in the hippocampus, cerebellum, and cortex during the postictal process.
Resumen Introducción La administración sistémica de pentilentetrazol (PTZ) causa daño cerebral y desencadena una serie de cambios morfológicos y neuroquímicos que a su vez provocan déficits conductuales, cognitivos y motores. Los niveles de serotonina (5-HT), dopamina (DA) y noradrenalina (NA) son modulados por varias estructuras cerebrales y sus concentraciones se relacionan con la actividad motora; sin embargo, se desconoce la concentración de estos neurotransmisores durante el proceso postictal. Objetivo Evaluar la manera en que la concentración de 5-HT, NA y DA en el hipocampo, el cerebelo y la corteza influye en el déficit motor durante la etapa postictal. Método Se utilizaron 18 ratas macho Wistar (300 g), divididas en dos grupos: control (n = 9, solución salina) y experimental (n = 9, PTZ). Se registraron las sacudidas mioclónicas y se evaluó el comportamiento motor durante tres horas después de la inyección de PTZ (90 mg/kg). Se extrajeron la corteza, el cerebelo y el hipocampo de cada rata para determinar la concentración de 5-HT, DA y NA mediante cromatografía líquida de alta resolución. Resultados La administración de PTZ indujo un aumento significativo en los niveles totales de 5-HT y DA en el hipocampo y la corteza; en el cerebelo hubo un aumento significativo en la concentración de 5-HT y NA. Se encontró una diferencia significativa entre el grupo experimental y control con respecto a las sacudidas mioclónicas; asimismo, los animales del grupo experimental mostraron un marcado déficit motor. Discusión y conclusión La 5-HT modula la concentración de otras monoaminas involucradas directamente en aspectos motores tal como NA y DA en el hipocampo, el cerebelo y la corteza durante el proceso postictal.
RESUMEN
INTRODUCTION/OBJECTIVES: The prevalence of chondrocalcinosis (CC) was reported as variable according to the geographic populations. However, there are no data regarding its prevalence in Mexico. Thus, we decided to investigate the Mexican prevalence of CC in a cohort of patients from a tertiary health care institution. METHODS: A retrospective analysis of radiographs of knees and wrists from our institution was performed. Inclusion criteria included patients > 50 years old having radiographs of knees and wrists. Radiographic presence of CC was classified according to a dichotomous evaluation assayed by two rheumatologists experts on the area. RESULTS: A total of 3.350 radiographs from 1.602 patients were evaluated. Forty-seven patients showed calcifications in at least one knee or wrist for an overall prevalence of 3%, of which 23.4% were men and 76.6% women. The knee was more commonly affected than the wrist (85.1% and 14.9% respectively). The prevalence according to gender was 2.9% in women, whereas, it was 3.2% in men. Only two patients (4.3%) showed a contemporaneous presence of CC in both hands and both knees. At knee level, the prevalence was 2.7%, whereas at the wrist, we reported a prevalence of 4.9%. CONCLUSIONS: The prevalence of CC for Mexican population had not been reported so far. This a starting point to break the silence and encourage the knowledge of how this disease is associated with possible risk factors in Mexican population. Key Points â¢The prevalence of chondrocalcinosis in Mexico was 3%. â¢The prevalence of knee chondrocalcinosis increases according to the age in women's. â¢The nixtamalized meals could be a protective factor for CC in Mexican population.
Asunto(s)
Condrocalcinosis/epidemiología , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Muñeca/diagnóstico por imagen , Anciano , Condrocalcinosis/diagnóstico por imagen , Femenino , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Prevalencia , Radiografía , Centros de Atención TerciariaRESUMEN
RATIONALE: The sensorimotor cortex and the striatum are interconnected by the corticostriatal pathway, suggesting that cortical injury alters the striatal function, which may be modulated by dopamine. OBJECTIVES: We studied whether the activation of dopamine D1 receptors (D1Rs) modulates the γ-aminobutyric acid (GABA) and glutamate levels in the striatum of recovered rats at 192 h after cortical injury. METHODS: The D1R agonist SKF-38393 (0, 2, 3, or 4 mg/kg) was administered at 24, 48, 96, and 192 h post-injury, and then rats were decapitated to determine GABA and glutamate levels and the levels of D1R mRNA on both sides of the striatum. RESULTS: GABAergic imbalance in the striatum contralateral to the injury site was normalized by the administration of the D1R agonist, but this treatment did not produce a significant effect on glutamate levels, suggesting that glutamate was metabolized into GABA. The administration of SKF-38393 (2 mg/kg) decreased the levels of D1R mRNA in the striatum contralateral to the injury, and this effect was blocked by the coadministration of the D1R antagonist SCH-23390 (2 mg/kg). In the striatum ipsilateral to the injury, the D1R agonist increased the D1R mRNA levels, an effect that was blocked by SCH-23390. CONCLUSION: The reversal of the GABAergic imbalance in the striatum contralateral to the cortical injury can be modulated by extrastriatal D1R activation, and the D1R agonist-induced increases in the D1R mRNA levels in the striatum ipsilateral to the injury suggest that the striatum may be necessary to achieve functional recovery.
Asunto(s)
Cuerpo Estriado/metabolismo , Receptores de Dopamina D1/metabolismo , Recuperación de la Función/fisiología , Corteza Sensoriomotora/lesiones , Corteza Sensoriomotora/metabolismo , Ácido gamma-Aminobutírico/metabolismo , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , Animales , Benzazepinas/farmacología , Cuerpo Estriado/efectos de los fármacos , Dopamina/metabolismo , Agonistas de Dopamina/farmacología , Antagonistas de Dopamina/farmacología , Masculino , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Ratas , Ratas Wistar , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/antagonistas & inhibidores , Recuperación de la Función/efectos de los fármacos , Corteza Sensoriomotora/efectos de los fármacosRESUMEN
RATIONALE: Histamine H3 receptors (H3Rs) are co-expressed with dopamine D1 receptors (D1Rs) by striato-nigral medium spiny GABAergic neurons, where they functionally antagonize D1R-mediated responses. OBJECTIVES AND METHODS: We examined whether the chronic administration of the H3R agonist immepip modifies dyskinesias induced by L-3,4-dihydroxyphenylalanine, L-Dopa (LIDs), in rats lesioned with 6-hydroxydopamine in the substantia nigra pars compacta, and the effect of D1R and H3R co-activation on glutamate and GABA content in dialysates from the dorsal striatum of naïve rats. RESULTS: The systemic administration (i.p.) of L-Dopa for 14 days significantly increased axial, limb, and orolingual abnormal involuntary movements (AIMs) compared with the vehicle group. The chronic administration of the H3R agonist immepip alongside L-Dopa significantly decreased axial, limb, and orolingual AIMs compared with L-Dopa alone, but AIMs returned to previous values on immepip withdrawal. Chronic immepip was ineffective when administered prior to L-Dopa. The chronic administration of immepip significantly decreased GABA and glutamate content in striatal dialysates, whereas the administration of L-Dopa alone increased GABA and glutamate content. CONCLUSIONS: These results indicate that chronic H3R activation reduces LIDs, and the effects on striatal GABA and glutamate release provide evidence for a functional interaction between D1Rs and H3Rs.
Asunto(s)
Discinesia Inducida por Medicamentos/tratamiento farmacológico , Agonistas de los Receptores Histamínicos/administración & dosificación , Imidazoles/administración & dosificación , Levodopa/toxicidad , Oxidopamina/toxicidad , Piperidinas/administración & dosificación , Receptores Histamínicos H3/fisiología , Animales , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Discinesia Inducida por Medicamentos/metabolismo , Masculino , Ratas , Ratas Wistar , Sustancia Negra/efectos de los fármacos , Sustancia Negra/metabolismoRESUMEN
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.
Asunto(s)
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
Dopamine (DA) modulates motor coordination, and its depletion, as in Parkinson's disease, produces motor impairment. The basal ganglia, cerebellum and cerebral cortex are interconnected, have functional roles in motor coordination, and possess dopamine D1 receptors (D1Rs), which are expressed at a particularly high density in the basal ganglia. In this study, we examined whether the activation of D1Rs modulates motor coordination and balance in the rat using a beam-walking test that has previously been used to detect motor coordination deficits. The systemic administration of the D1R agonist SKF-38393 at 2, 3, or 4 mg/kg did not alter the beam-walking scores, but the subsequent administration of the D1R antagonist SCH-23390 at 1 mg/kg did produce deficits in motor coordination, which were reversed by the full agonist SKF-82958. The co-administration of SKF-38393 and SCH-23390 did not alter the beam-walking scores compared with the control group, but significantly prevented the increase in beam-walking scores induced by SCH-23390. The effect of the D1R agonist to prevent and reverse the effect of the D1R antagonist in beam-walking scores is an indicator that the function of D1Rs is necessary to maintain motor coordination and balance in rats. Our results support that D1Rs mediate the SCH-23390-induced deficit in motor coordination.
Asunto(s)
Cuerpo Estriado/efectos de los fármacos , Agonistas de Dopamina/farmacología , Actividad Motora/efectos de los fármacos , Enfermedad de Parkinson/tratamiento farmacológico , Receptores de Dopamina D1/efectos de los fármacos , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , Animales , Benzazepinas/farmacología , Masculino , Equilibrio Postural/efectos de los fármacos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismoRESUMEN
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.
Asunto(s)
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 noradrenergic and dopaminergic systems are associated with the motor system and have anatomical and functional connections that have not yet been studied. The present study aimed to examine the specific role of D1 receptors (D1Rs) on noradrenergic and dopaminergic responses in the rat brain. Male Wistar rats were assigned to eight groups to receive systemic injection of a D1R agonist (SKF-38393) at 0, 1, 5 or 10mg/kg or injection of a D1R antagonist (SCH-23390) at 0, 0.25, 0.5 or 1mg/kg. Dopamine (DA) and noradrenaline (NA) levels were measured using high-performance liquid chromatography. Injection of SKF-38393 alone at 1, 5 and 10mg/kg did not alter DA levels in the midbrain, cerebral cortex or pons, while it significantly increased these levels in the striatum (at 1 and 10mg/kg), hippocampus (at 1mg/kg) and cerebellum (at 1 and 5mg/kg). Administration of SKF-38393 at 1, 5, and 10mg/kg decreased the NA levels in the midbrain, pons, hippocampus (except at 1mg/kg) and cortex (except at 5mg/kg), whereas the opposite effect was observed in the striatum. SCH-23390 decreased the DA levels in the cortex (at 0.25 and 0.5mg/kg) and pons (at 0.5mg/kg). In contrast, 0.25, 0.5 and 1mg/kg SCH-23390 increased the DA levels in the cerebellum, whereas no differences from the control levels were observed for the DA levels in the striatum, midbrain and hippocampus. SCH-23390 at 0.5 and 1mg/kg increased the NA levels in the striatum. In contrast, the midbrain, hippocampus, cortex, pons and cerebellum did not exhibit altered NA levels. Our results demonstrate that the activation of D1Rs modulates the response of the noradrenergic system in nearly all of the investigated brain structures; thus, the blockade of D1Rs attenuates the effects induced by D1R activation.
Asunto(s)
Encéfalo/efectos de los fármacos , Dopamina/metabolismo , Norepinefrina/metabolismo , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/antagonistas & inhibidores , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , Animales , Benzazepinas/farmacología , Encéfalo/metabolismo , Masculino , Ratas WistarRESUMEN
Monoamines such as norepinephrine (NE) and serotonin (5-HT) have shown to play an important role in motor recovery after brain injury. The effects elicited by these neurotransmitters have been reported as distal from the area directly affected. Remote changes may take place over minutes to weeks and play an important role in post-stroke recovery. However, the mechanisms involved in spontaneous recovery have not been thoroughly delineated. Therefore, we determined the NE and 5-HT content, in the pons and hippocampal dentate gyrus (DG) as well as motor deficit and spontaneous activity in rats after 3, 10 and 20 days cortical iron injection. Three days post-lesion the pontine NE content diminished, this effect was accompanied by deficient spontaneous activity and impaired sensorimotor evaluation. Ten and twenty days after lesion the NE levels were similar to those of control group, and animals also showed behavioral recovery. Monoamines content on DG 3 days post-lesion showed no differences as compared to controls. Interestingly, ten and twenty days after cortical injury, animals showed increased NE and 5-HT. These results suggest that behavioral recovery after brain damage involve changes on monoamines levels on DG, an important structure to plastic processes. In addition, the results herein support evidence to propose these neurotransmitters as key molecules to functional recovery in the central nervous system.
Asunto(s)
Lesiones Encefálicas/metabolismo , Giro Dentado/metabolismo , Norepinefrina/metabolismo , Puente/metabolismo , Recuperación de la Función/fisiología , Serotonina/metabolismo , Animales , Lesiones Encefálicas/complicaciones , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Compuestos Ferrosos , Masculino , Actividad Motora/fisiología , Trastornos del Movimiento/etiología , Trastornos del Movimiento/metabolismo , Plasticidad Neuronal/fisiología , Distribución Aleatoria , 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.
Asunto(s)
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
Introducción y objetivos. La audición residual se considera uno de los factores pronósticos para la evolución de pacientes con implante coclear, y su determinación de manera objetiva a través de potenciales evocados auditivos de estado estable (PEAee) es de suma importancia. Los objetivos en este estudio fueron cuantificar la audición residual y evaluar la utilidad de los PEAee en su medición en pacientes implantados. Métodos. A 12 pacientes con implante coclear se les aplicó audiometría tonal liminar (ATL) pre y postimplantación, así como PEAee postimplante. Se realizó estadística descriptiva, correlaciones de Pearson y tablas de contingencia. Resultados. Se conservó la audición residual en el 37,5% de los pacientes para la frecuencia de 125 Hz; para 250 y 500 Hz, la conservaron el 45,45% de los pacientes; en 1.000 Hz, el 27,27%; en 2.000 Hz, el 28,85% conservó la audición posterior al implante coclear; en 4.000 Hz, el 16%, y el 0% en el caso de 8.000 Hz. Al realizar PEAee postimplante se observa que no hay respuesta en el oído implantado, en comparación con el oído no implantado, donde encontramos respuesta en las frecuencias de 500 y 1.000 Hz, dado que los pacientes eran portadores de hipoacusia bilateral profunda, lo que podría evidenciar destrucción parcial del tejido neural en el oído implantado. Conclusiones. La audición residual en frecuencias graves se conservó en la mayor parte de los pacientes. Los resultados en PEAee sugieren que es un estudio útil para evaluar la audición residual(AU)
Background and objectives. Residual hearing is considered a prognostic factor in patients with cochlear implants. Objective determination of residual hearing by steady-state evoked potential (SSEP) is of the utmost importance. The aims of this study were to quantify residual hearing and evaluate the usefulness of SSEP measurement in patients with cochlear implants. Methods. Liminal pure-tone audiometry was applied in 12 patients before and after cochlear implantation. SSEP were evaluated post-implantation. Descriptive statistics and Pearson correlations were carried out and contingency tables were constructed. Results. Residual hearing at a frequency of 125 Hz was preserved in 37.5% of the patients, at 250 and 500 Hz in 45.45%, and at 1000 Hz in 27.27%. After implantation, residual hearing at 2000 Hz was retained in 28.85%, at 4000 Hz in 16%, and at 8000 Hz in 0%. Post-implantation SSEP showed no response in the implanted ear as compared with the non-implanted ear at frequencies of 500 and 1000 Hz. Because the patients had bilateral profound hearing loss, this finding suggested partial destruction of the neural tissue in the implanted ear. Conclusions. Residual low frequency hearing was preserved in most patients. Our results suggest that SSEP is useful in the assessment of residual hearing(AU)
Asunto(s)
Humanos , Masculino , Femenino , Fonoaudiología/métodos , Audición/fisiología , Pérdida Auditiva Súbita/complicaciones , Pérdida Auditiva Súbita/diagnóstico , Implantes Cocleares , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Pérdida Auditiva/cirugía , Pérdida Auditiva , Pruebas de Impedancia Acústica/instrumentación , Pruebas de Impedancia Acústica/métodos , Audiometría/instrumentación , Audiometría/métodos , Audiometría , Implantación Coclear/métodos , Implantación Coclear/normas , Implantación CoclearRESUMEN
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.
Asunto(s)
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.