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1.
Int J Mol Sci ; 25(10)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38791229

RESUMEN

Parkinson's disease (PD) is a progressive disorder characterized by the apoptosis of dopaminergic neurons in the basal ganglia. This study explored the potential effects of aminophylline, a non-selective adenosine A1 and A2A receptor antagonist, on catalepsy and gait in a haloperidol-induced PD model. Sixty adult male Swiss mice were surgically implanted with guide cannulas that targeted the basal ganglia. After seven days, the mice received intraperitoneal injections of either haloperidol (experimental group, PD-induced model) or saline solution (control group, non-PD-induced model), followed by intracerebral infusions of aminophylline. The assessments included catalepsy testing on the bar and gait analysis using the Open Field Maze. A two-way repeated-measures analysis of variance (ANOVA), followed by Tukey's post hoc tests, was employed to evaluate the impact of groups (experimental × control), aminophylline (60 nM × 120 nM × saline/placebo), and interactions. Significance was set at 5%. The results revealed that the systemic administration of haloperidol in the experimental group increased catalepsy and dysfunction of gait that paralleled the observations in PD. Co-treatment with aminophylline at 60 nM and 120 nM reversed catalepsy in the experimental group but did not restore the normal gait pattern of the animals. In the non-PD induced group, which did not present any signs of catalepsy or motor dysfunctions, the intracerebral dose of aminophylline did not exert any interference on reaction time for catalepsy but increased walking distance in the Open Field Maze. Considering the results, this study highlights important adenosine interactions in the basal ganglia of animals with and without signs comparable to those of PD. These findings offer valuable insights into the neurobiology of PD and emphasize the importance of exploring novel therapeutic strategies to improve patient's catalepsy and gait.


Asunto(s)
Aminofilina , Catalepsia , Modelos Animales de Enfermedad , Marcha , Haloperidol , Enfermedad de Parkinson , Animales , Catalepsia/tratamiento farmacológico , Catalepsia/inducido químicamente , Ratones , Masculino , Aminofilina/administración & dosificación , Aminofilina/farmacología , Aminofilina/uso terapéutico , Marcha/efectos de los fármacos , Haloperidol/administración & dosificación , Haloperidol/farmacología , Enfermedad de Parkinson/tratamiento farmacológico
2.
Rev. bras. med. esporte ; Rev. bras. med. esporte;27(spe2): 91-94, Apr.-June 2021. graf
Artículo en Inglés | LILACS | ID: biblio-1280083

RESUMEN

ABSTRACT Racewalking fatigue is a kind of fatigue symptom after a period of racewalking, which may lead to limb weakness, mental fatigue, muscle fatigue and other phenomena. If we do not timely adjust the stretching and effective treatment after exercise, it is very easy to produce sports injury and seriously affect the athletes' physical function. In order to effectively alleviate the fatigue of racewalking, this study focused on the traditional Chinese medicine (TCM) compounded medication, analyzed the mechanism of action and medicinal effectiveness of the TCM compound, and carried out control experiment on 80 male ICR mice. The mice in the experimental group were given sedentary training and racewalking training in groups. The results showed that the two groups of ICR mice, after racewalking training, had exercise fatigue symptoms and a large amount of serum lactic acid and other substances, while mice in group D treated by gavage of traditional Chinese medicine compounded medication had the symptoms of exercise fatigue, but the contents of blood urea nitrogen and lactic acid were decreased, the gastrocnemius muscle fibers were evenly arranged, the transverse lines were neat, and a rebound of protein expression. This shows that Chinese medicine compound can play a significant role in relieving racewalking fatigue.


RESUMO A fadiga causada pela marcha atlética é um tipo de sintoma que acomete os atletas após um período de prática do exercício, que pode ocasionar fraqueza dos membros, fadiga mental, fadiga muscular e outros fenômenos. Na ausência de alongamento e tratamento eficaz após o exercício, as lesões causadas pelo esporte podem afetar seriamente a função física dos atletas. A fim de aliviar de maneira eficaz a fadiga causada pela marcha atlética, o presente estudo se concentrou nos medicamentos manipulados na medicina tradicional chinesa (MTC), analisou o mecanismo de ação e eficácia medicinal dos medicamentos da MTC, e realizou experimentos de controle em 80 camundongos do tipo ICR masculinos. Os camundongos do grupo experimental receberam treinamento sedentário e treinamento de corrida em grupo. Os resultados mostraram que os dois grupos de camundongos ICR, após treino de marcha atlética, apresentavam sintomas de fadiga, e grande quantidade de ácido láctico sérico, além de outras substâncias, enquanto os camundongos do grupo D tratados com gavagem do medicamento manipulado tiveram sintomas de fadiga, mas com redução do teor sanguíneo de ureia e ácido láctico, fibras musculares gastrocnêmias uniformemente arranjadas, linhas transversais regulares, e efeito rebote da expressão proteica. Isto mostra que os medicamentos manipulados da medicina chinesa podem desempenhar um papel significativo no alívio da fadiga causada pela marcha atlética.


RESUMEN La fatiga causada por la marcha atlética es un tipo de síntoma que afecta los atletas después de un período de práctica del ejercicio, que puede ocasionar debilidad de los miembros, fatiga mental, fatiga muscular y otros fenómenos. En ausencia de elongación y tratamiento eficaz después del ejercicio, las lesiones causadas por el deporte pueden afectar seriamente la función física de los atletas. A fin de aliviar de manera eficaz la fatiga causada por la marcha atlética, el presente estudio se concentró en los medicamentos manipulados en la medicina tradicional china (MTC), analizó el mecanismo de acción y eficacia medicinal de los medicamentos da MTC, y realizó experimentos de control en 80 ratones del tipo ICR masculinos. Los ratones del grupo experimental recibieron entrenamiento sedentario y entrenamiento de carrera en grupo. Los resultados mostraron que los dos grupos de ratones ICR, después de entrenamiento de marcha atlética, presentaban síntomas de fatiga, y gran cantidad de ácido láctico sérico, además de otras sustancias, mientras que los ratones del grupo D tratados con gavaje del medicamento manipulado tuvieron síntomas de fatiga, pero con reducción del tenor sanguíneo de urea y ácido láctico, fibras musculares del gastrocnemio uniformemente arregladas, líneas transversales regulares, y efecto rebote de la expresión proteica. Esto muestra que los medicamentos manipulados de la medicina china pueden desempeñar un papel significativo en el alivio de la fatiga causada por la marcha atlética.


Asunto(s)
Animales , Masculino , Ratones , Condicionamiento Físico Animal , Fatiga/prevención & control , Atletas , Marcha/efectos de los fármacos , Medicina Tradicional China
3.
Mol Cell Neurosci ; 114: 103632, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34058345

RESUMEN

Duchenne muscular dystrophy (DMD) is a genetic disease linked to the X chromosome induced by mutations in the dystrophin gene. Neuroprotective drugs, such as pregabalin (PGB), can improve motor function through the modulation of excitatory synapses, together with anti-apoptotic and anti-inflammatory effects. The present work studied the effects of PGB in the preservation of dystrophic peripheral nerves, allowing motor improvements in MDX mice. Five weeks old MDX and C57BL/10 mice were treated with PGB (30 mg/kg/day, i.p.) or vehicle, for 28 consecutive days. The mice were sacrificed on the 9th week, the sciatic nerves were dissected out and processed for immunohistochemistry and qRT-PCR, for evaluating the expression of proteins and gene transcripts related to neuronal activity and Schwann cell function. The lumbar spinal cords were also processed for qRT-PCR to evaluate the expression of neurotrophic factors and pro- and anti-inflammatory cytokines. Cranial tibial muscles were dissected out for endplate evaluation with α-bungarotoxin. The recovery of motor function was monitored throughout the treatment, using a spontaneous walking track test (Catwalk system) and a forced locomotion test (Rotarod). The results showed that treatment with PGB reduced the retrograde effects of muscle degeneration/regeneration on the nervous system from the 5th to the 9th week in MDX mice. Thus, PGB induced protein expression in neurons and Schwann cells, protecting myelinated fibers. In turn, better axonal morphology and close-to-normal motor endplates were observed. Indeed, such effects resulted in improved motor coordination of dystrophic animals. We believe that treatment with PGB improved the balance between excitatory and inhibitory inputs to spinal motoneurons, increasing motor control. In addition, PGB enhanced peripheral nerve homeostasis, by positively affecting Schwann cells. In general, the present results indicate that pregabalin is effective in protecting the PNS during the development of DMD, improving motor coordination, indicating possible translation to the clinic.


Asunto(s)
Marcha/efectos de los fármacos , Distrofia Muscular de Duchenne/fisiopatología , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Pregabalina/farmacología , Nervio Ciático/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos mdx , Distrofia Muscular de Duchenne/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Pregabalina/uso terapéutico , Recuperación de la Función/efectos de los fármacos , Nervio Ciático/fisiopatología
4.
Eur J Pharmacol ; 890: 173636, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33053380

RESUMEN

Inflammatory arthritis, such as rheumatoid arthritis (RA), stands out as one of the main sources of pain and impairment to the quality of life. The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models, but its effect on neuro-inflammatory aspects of RA is limited. In this study, antigen-induced arthritis (AIA) was evoked by the intraarticular (i.art.) injection of methylated bovine serum albumin (mBSA) in male Sprague Dawley rats. Phosphate buffered saline (PBS)-injected ipsilateral knee joints or AIA contralateral were used as control. Nociceptive and inflammatory parameters such as knee joint oedema and leukocyte influx and histopathological changes were carried out in addition to the local measurement of interleukins (IL) IL-6, IL-1ß, tumor necrosis factor-α and the immunoreactivity of the neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord (lumbar L3-5 segments) of AIA rats. For 4 days, AIA rats were treated daily with a single administration of saline, Hp injected (10 or 20 µg/day, i.art.), Hp given orally (20 µg/Kg, p.o.) or indomethacin (Indo; 5 mg/Kg, i.p.). In comparison to the PBS control group, the induction of AIA produced a significant and progressive mono-arthritis condition. The degree of AIA severity progressively compromised the normal walking pattern and impaired mobility over the next four days in relation to PBS-injected rats or contralateral knee joints. In AIA rats, the reduction of the distance between footprints and disturbances of gait evidenced signs of nociception. This response worsened at day 4, and a loss of footprint from the ipsilateral hind paw was evident. Daily treatment of the animals with Hp either i.art. (10 and 20 µg/knee) or p.o. (20 µg/Kg) as well as Indo (5 mg/Kg, i.p.) ameliorated the impaired mobility in a time-dependent manner (P < 0.05). In parallel, the AIA-injected ipsilateral knee joints reach a peak of swelling 24 h after AIA induction, which persisted over the next four days in relation to PBS-injected rats or contralateral knee joints. There was a significant but not dose-dependent inhibitory effect produced by all dosages and routes of Hp treatments on AIA-induced knee joint swelling (P < 0.05). In addition, the increased synovial levels of MPO activity, total leukocytes number and IL-6, but not IL-1ß, were significantly reduced by the lower i.art. dose of Hp. In conclusion, these results successfully demonstrate that Hp may represent a novel therapeutic strategy to treat RA, an effect which is unrelated to the proinflammatory actions of the neuropeptides CGRP and SP.


Asunto(s)
Antiinflamatorios/farmacología , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Hemoglobinas/farmacología , Dolor Nociceptivo/prevención & control , Fragmentos de Péptidos/farmacología , Administración Oral , Animales , Antiinflamatorios/administración & dosificación , Conducta Animal/efectos de los fármacos , Citocinas/metabolismo , Edema/tratamiento farmacológico , Marcha/efectos de los fármacos , Hemoglobinas/administración & dosificación , Inflamación/tratamiento farmacológico , Inyecciones Intraarticulares , Articulación de la Rodilla/efectos de los fármacos , Articulación de la Rodilla/metabolismo , Articulación de la Rodilla/patología , Leucocitos/efectos de los fármacos , Masculino , Fragmentos de Péptidos/administración & dosificación , Ratas Sprague-Dawley , Receptores de Péptido Relacionado con el Gen de Calcitonina/metabolismo , Sustancia P/metabolismo
5.
Neurorehabil Neural Repair ; 34(7): 589-599, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32449460

RESUMEN

Background. Although dopaminergic medication improves dual task walking in people with Parkinson disease (PD), the underlying neural mechanisms are not yet fully understood. As prefrontal cognitive resources are involved in dual task walking, evaluation of the prefrontal cortex (PFC) is required. Objective. To investigate the effect of dopaminergic medication on PFC activity and gait parameters during dual task walking in people with PD. Methods. A total of 20 individuals with PD (69.8 ± 5.9 years) and 30 healthy older people (68.0 ± 5.6 years) performed 2 walking conditions: single and dual task (walking while performing a digit vigilance task). A mobile functional near infrared spectroscopy system and an electronic sensor carpet were used to analyze PFC activation and gait parameters, respectively. Relative concentrations of oxygenated hemoglobin (HbO2) from the left and right PFC were measured. Results. People with PD in the off state did not present changes in HbO2 level in the left PFC across walking conditions. In contrast, in the on state, they presented increased HbO2 levels during dual task compared with single task. Regardless of medication state, people with PD presented increased HbO2 levels in the right PFC during dual task walking compared with single task. The control group demonstrated increased PFC activity in both hemispheres during dual task compared with single task. People with PD showed increases in both step length and velocity in the on state compared with the off state. Conclusions. PD limits the activation of the left PFC during dual task walking, and dopaminergic medication facilitates its recruitment.


Asunto(s)
Dopaminérgicos/farmacología , Función Ejecutiva/efectos de los fármacos , Marcha/efectos de los fármacos , Levodopa/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Corteza Prefrontal/efectos de los fármacos , Desempeño Psicomotor/efectos de los fármacos , Anciano , Función Ejecutiva/fisiología , Femenino , Neuroimagen Funcional , Marcha/fisiología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Desempeño Psicomotor/fisiología , Espectroscopía Infrarroja Corta
6.
PLoS One ; 14(1): e0208827, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30605469

RESUMEN

This experiment was carried out aiming to assess walking manner and speed of broiler chickens with different gait scores (GS), with or without sound stimulus, and with or without administration of analgesic. To that end, 1,000 birds were evaluated by the GS test and 74 were selected for walking speed analyses. Weight at slaughter and breast yield values were obtained for comparisons. Walking speed analyses, both with and without analgesic and with and without stimulus were performed. Non-parametric statistics was applied to the GS data that did not meet the assumptions of the statistical model (normality and homogenicity) using Fisher's exact test according to the data behavior (P<0.05). The analyses of data on speed, weight at slaughter, and breast yield were evaluated by ANOVA and compared by Tukey's test (P<0.05). Walking speed differed after acoustic stimulus with or without administration of metamizole sodium. Body weight was also different in each GS. It is thus concluded that the birds may feel discomfort when their GS is higher than 0, but that such discomfort may be suppressed when they are stimulated to walk.


Asunto(s)
Analgésicos/farmacología , Marcha/fisiología , Animales , Peso Corporal/efectos de los fármacos , Pollos , Dipirona/farmacología , Marcha/efectos de los fármacos , Programas Informáticos
7.
Arq Neuropsiquiatr ; 76(3): 183-188, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29809239

RESUMEN

Motor and non-motor manifestations are common and disabling features of hereditary spastic paraplegia (HSP). Botulinum toxin type A (Btx-A) is considered effective for spasticity and may improve gait in these patients. Little is known about the effects of Btx-A on non-motor symptoms in HSP patients. Objective To assess the efficacy of Btx-A on motor and non-motor manifestations in HSP patients. Methods Thirty-three adult patients with a clinical and molecular diagnosis of HSP were evaluated before and after Btx-A injections. Results Mean age was 41.7 ± 13.6 years and there were 18 women. Most patients had a pure phenotype and SPG4 was the most frequent genotype. The Btx-A injections resulted in a decrease in spasticity at the adductor muscles, and no other motor measure was significantly modified. In contrast, fatigue scores were significantly reduced after Btx-A injections. Conclusion Btx-A injections resulted in no significant functional motor improvement for HSP, but fatigue improved after treatment.


Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Trastornos Motores/tratamiento farmacológico , Trastornos Motores/fisiopatología , Fármacos Neuromusculares/uso terapéutico , Paraplejía Espástica Hereditaria/tratamiento farmacológico , Paraplejía Espástica Hereditaria/fisiopatología , Adulto , Edad de Inicio , Femenino , Marcha/efectos de los fármacos , Marcha/fisiología , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Fatiga Muscular/efectos de los fármacos , Fatiga Muscular/fisiología , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/fisiopatología , Reproducibilidad de los Resultados , Resultado del Tratamiento
8.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;76(3): 183-188, Mar. 2018. tab, graf
Artículo en Inglés | LILACS | ID: biblio-888373

RESUMEN

ABSTRACT Motor and non-motor manifestations are common and disabling features of hereditary spastic paraplegia (HSP). Botulinum toxin type A (Btx-A) is considered effective for spasticity and may improve gait in these patients. Little is known about the effects of Btx-A on non-motor symptoms in HSP patients. Objective To assess the efficacy of Btx-A on motor and non-motor manifestations in HSP patients. Methods Thirty-three adult patients with a clinical and molecular diagnosis of HSP were evaluated before and after Btx-A injections. Results Mean age was 41.7 ± 13.6 years and there were 18 women. Most patients had a pure phenotype and SPG4 was the most frequent genotype. The Btx-A injections resulted in a decrease in spasticity at the adductor muscles, and no other motor measure was significantly modified. In contrast, fatigue scores were significantly reduced after Btx-A injections. Conclusion Btx-A injections resulted in no significant functional motor improvement for HSP, but fatigue improved after treatment.


RESUMO Manifestações motoras e não motoras são comuns e incapacitantes nas paraparesias espásticas hereditárias (PEH). Toxina botulínica do tipo A (TB-A) é considerada eficaz no tratamento da espasticidade e pode melhorar a marcha nesses pacientes. Pouco se sabe sobre os efeitos da TB-A sobre sintomas não-motores. Objetivo avaliar a eficácia da TB-A sobre manifestações motoras e não-motoras nas PEH. Método trinta e três pacientes adultos com PEH foram avaliados antes e depois das aplicações de TB-A. Resultados A média de idade foi 41,7 ± 13,6 anos e havia 18 mulheres. A maioria dos pacientes portava a forma pura e o genótipo mais comum foi SPG4. Houve diminuição da espasticidade dos músculos adutores da coxa sem melhora da marcha. A pontuação da fadiga reduziu após as injeções. Conclusão As aplicações de TB-A não melhoraram a marcha nos pacientes mas a redução da fadiga foi significativa após o tratamento.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Paraplejía Espástica Hereditaria/fisiopatología , Paraplejía Espástica Hereditaria/tratamiento farmacológico , Toxinas Botulínicas Tipo A/uso terapéutico , Trastornos Motores/fisiopatología , Trastornos Motores/tratamiento farmacológico , Fármacos Neuromusculares/uso terapéutico , Reproducibilidad de los Resultados , Resultado del Tratamiento , Edad de Inicio , Fatiga Muscular/efectos de los fármacos , Fatiga Muscular/fisiología , Marcha/efectos de los fármacos , Marcha/fisiología , Inyecciones Intramusculares , Espasticidad Muscular/tratamiento farmacológico
9.
J Mot Behav ; 50(1): 17-25, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28632105

RESUMEN

The authors' aim was to investigate gait asymmetry of crossing step during obstacle avoidance while walking in people with Parkinson's disease (PD) under and without the effects of dopaminergic medication. Thirteen individuals with PD and 13 neurologically healthy individuals performed 5 trials of unobstructed gait and 10 trials of obstacle crossing during gait (5 trials with each leg) and spatiotemporal parameters were analyzed. Obstacle crossing increased step duration of the crossing step for the most-affected or nondominant limb compared to the crossing step with the least-affected or dominant limb. Individuals with PD without the effects of medication increased step duration for the step with the least-affected limb compared to the step with the most-affected limb during obstacle crossing.


Asunto(s)
Dopaminérgicos/uso terapéutico , Trastornos Neurológicos de la Marcha/fisiopatología , Marcha/fisiología , Enfermedad de Parkinson/fisiopatología , Anciano , Dopaminérgicos/farmacología , Femenino , Marcha/efectos de los fármacos , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológico , Caminata/fisiología
10.
Physiol Rep ; 5(6)2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28351968

RESUMEN

The aim of this study was to evaluate the effects of two gamma-amino butyric acid (GABA)a receptor antagonists on motor behavioral tasks in a pharmacological model of Parkinson disease (PD) in rodents. Ninety-six Swiss mice received intraperitoneal injection of Haloperidol (1 mg/kg) to block dopaminergic receptors. GABAa receptors antagonists Bicuculline (1 and 5 mg/kg) and Flumazenil (3 and 6 mg/kg) were used for the assessment of the interaction among these neurotransmitters, in this PD model. The motor behavior of the animals was evaluated in the catalepsy test (30, 60, and 90 min after drugs application), through open field test (after 60 min) and trough functional gait assessment (after 60 min). Both Bicuculline and Flumazenil were able to partially reverse catalepsy induced by Haloperidol. In the open field test, Haloperidol reduced the number of horizontal and vertical exploration of the animals, which was not reversed trough application of GABAa antagonists. Furthermore, the functional gait assessment was not sensitive enough to detect motor changes in this animal model of PD. There is an interaction between dopamine and GABA in the basal ganglia and the blocking GABAa receptors may have therapeutic potential in the treatment of PD.


Asunto(s)
Antagonistas de Receptores de GABA-A/farmacología , Marcha/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Trastornos Parkinsonianos/fisiopatología , Animales , Conducta Animal/efectos de los fármacos , Bicuculina/farmacología , Modelos Animales de Enfermedad , Flumazenil/farmacología , Ratones
11.
Neuropharmacology ; 117: 85-92, 2017 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-28161374

RESUMEN

Inhibitory GABAergic and glycinergic neurotransmission in the spinal cord play a central role in the regulation of neuronal excitability, by maintaining a balance with the glutamate-mediated excitatory transmission. Glutamatergic agonists infusion in the spinal cord induce motor neuron death by excitotoxicity, leading to motor deficits and paralysis, but little is known on the effect of the blockade of inhibitory transmission. In this work we studied the effects of GABAergic and glycinergic blockade, by means of microdialysis perfusion (acute administration) and osmotic minipumps infusion (chronic administration) of GABA and glycine receptors antagonists directly in the lumbar spinal cord. We show that acute glycinergic blockade with strychnine or GABAergic blockade with bicuculline had no significant effects on motor activity and on motor neuron survival. However, chronic bicuculline infusion, but not strychnine, induced ipsilateral gait alterations, phalange flaccidity and significant motor neuron loss, and these effects were prevented by AMPA receptor blockade with CNQX but not by NMDA receptor blockade with MK801. In addition, we demonstrate that the chronic infusion of bicuculline enhanced the excitotoxic effect of AMPA, causing faster bilateral paralysis and increasing motor neuron loss. These findings indicate a relevant role of GABAergic inhibitory circuits in the regulation of motor neuron excitability and suggest that their alterations may be involved in the neurodegeneration processes characteristic of motor neuron diseases such as amyotrophic lateral sclerosis.


Asunto(s)
Bicuculina/toxicidad , Antagonistas del GABA/toxicidad , Actividad Motora/efectos de los fármacos , Neuronas Motoras/efectos de los fármacos , Degeneración Nerviosa/inducido químicamente , Médula Espinal/efectos de los fármacos , Estricnina/toxicidad , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Animales , Atrofia/inducido químicamente , Bicuculina/antagonistas & inhibidores , Maleato de Dizocilpina/farmacología , Interacciones Farmacológicas , Marcha/efectos de los fármacos , Masculino , Hipotonía Muscular/inducido químicamente , Ratas , Receptores de Glicina/antagonistas & inhibidores , Estricnina/antagonistas & inhibidores , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/toxicidad
12.
Rev Med Inst Mex Seguro Soc ; 55(1): 18-24, 2017.
Artículo en Español | MEDLINE | ID: mdl-28092243

RESUMEN

BACKGROUND: Cerebral palsy (PCI) is the leading cause of disability in children. Botulinum toxin type A (TBA) is a treatment to improve the function and pattern in the gait, although with a few studies that quantify the improvement. METHODS: Quasi-experimental study was conducted from May 2010 to September 2011, in Integrated Rehabilitation Center, in 36 patients with spastic PCI. Was evaluated: functionality of travel by the scale of Koman, speed of the gait with tone scale of Ashworth and arches of passive mobility, were applied TBA and was sent to 10 sessions of physical therapy, with measurements taken before, the 1st and 4th month. RESULTS: 30 Patients completed the study, between the ages of 2 and 12 years, the majority had improvement in the functionality of the gear, tone, dorsiflexion and abduction of ankles to the motion, which was maintained at 4 months. CONCLUSIONS: Botulinum toxin is an effective treatment to increase the arches of mobility and functionality of the gait of patients with hemiparesis and spastic paraparesis.


Introducción: La parálisis cerebral (PCI) es la principal causa de discapacidad en la infancia. La toxina botulínica tipo A (TBA) es un tratamiento para mejorar la función y patrón en la marcha, aunque con pocos estudios que cuantifiquen la mejoría. Métodos: Se realizó un estudio cuasiexperimental, de mayo de 2010 a septiembre de 2011, en un centro de rehabilitación integral, participaron 36 pacientes con PCI espástica. Se evaluó: funcionalidad de la marcha por la escala de Koman, velocidad de desplazamiento de la marcha, tono con escala de Ashworth y arcos de movilidad pasivas. Se les aplicó TBA y se les envió a 10 sesiones de terapia física, con mediciones antes, al mes 1 y 4. Resultados: 30 pacientes terminaron el estudio, con edades entre 2 y 12 años, la mayoría tuvieron mejoría en la funcionalidad de la marcha, tono, dorsiflexión y abducción de tobillos al mes, que se mantuvo a los 4 meses. Conclusiones: La toxina botulínica es un tratamiento eficaz para aumentar los arcos de movilidad y la funcionalidad de la marcha en los pacientes con hemiparesia y paraparesia espástica.


Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Parálisis Cerebral/terapia , Fármacos Neuromusculares/uso terapéutico , Modalidades de Fisioterapia , Toxinas Botulínicas Tipo A/farmacología , Niño , Preescolar , Terapia Combinada , Esquema de Medicación , Femenino , Estudios de Seguimiento , Marcha/efectos de los fármacos , Humanos , Masculino , Fármacos Neuromusculares/farmacología , Resultado del Tratamiento
13.
Expert Opin Pharmacother ; 17(18): 2405-2415, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27785919

RESUMEN

INTRODUCTION: Dopamine depletion is one of the most important features of Parkinson's Disease (PD). However, insufficient response to dopaminergic replacement therapy suggests the involvement of other neurotransmitter systems in the pathophysiology of PD. Cholinergic degeneration contributes to gait impairments, cognitive impairment, psychosis, and REM-sleep disturbances, among other symptoms. Areas covered: In this review, we explore the idea that enhancing cholinergic tone by pharmacological or neurosurgical procedures could be a first-line therapeutic strategy for the treatment of symptoms derived from cholinergic degeneration in PD. Expert opinion: Rivastigmine, a drug that increases cholinergic tone by inhibiting the enzyme cholinesterase, is effective for dementia, whereas the use of Donepezil is still in the realm of investigation. Interesting results suggest the efficacy of these drugs in the treatment of gait dysfunction. Evidence on the clinical effects of these drugs for psychosis and REM-sleep disturbances is still weak. Stimulation of the pedunculo-pontine tegmental nuclei (which provide cholinergic innervation to the brain stem and subcortical nuclei) has also been used with some success for the treatment of gait dysfunction. Anticholinergic drugs should be used with caution in PD, as they may aggravate cholinergic symptoms. Notwithstanding, in some patients they might help control parkinsonian motor symptoms.


Asunto(s)
Colinérgicos/uso terapéutico , Neuronas Colinérgicas/patología , Degeneración Nerviosa/tratamiento farmacológico , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Colinérgicos/farmacología , Neuronas Colinérgicas/efectos de los fármacos , Ensayos Clínicos como Asunto/métodos , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/epidemiología , Demencia/diagnóstico , Demencia/dietoterapia , Demencia/epidemiología , Donepezilo , Marcha/efectos de los fármacos , Humanos , Indanos/farmacología , Indanos/uso terapéutico , Degeneración Nerviosa/diagnóstico , Degeneración Nerviosa/epidemiología , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/epidemiología , Piperidinas/farmacología , Piperidinas/uso terapéutico , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/epidemiología
14.
Brain Behav ; 4(5): 738-53, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25328849

RESUMEN

BACKGROUND: G-CSF has been shown to decrease inflammatory processes and to act positively on the process of peripheral nerve regeneration during the course of muscular dystrophy. AIMS: The aims of this study were to investigate the effects of treatment of G-CSF during sciatic nerve regeneration and histological analysis in the soleus muscle in MDX mice. METHODS: Six-week-old male MDX mice underwent left sciatic nerve crush and were G-CSF treated at 7 days prior to and 21 days after crush. Ten and twenty-one days after surgery, the mice were euthanized, and the sciatic nerves were processed for immunohistochemistry (anti-p75(NTR) and anti-neurofilament) and transmission electron microscopy. The soleus muscles were dissected out and processed for H&E staining and subsequent morphologic analysis. Motor function analyses were performed at 7 days prior to and 21 days after sciatic crush using the CatWalk system and the sciatic nerve index. RESULTS: Both groups treated with G-CSF showed increased p75(NTR) and neurofilament expression after sciatic crush. G-CSF treatment decreased the number of degenerated and regenerated muscle fibers, thereby increasing the number of normal muscle fibers. CONCLUSIONS: The reduction in p75(NTR) and neurofilament indicates a decreased regenerative capacity in MDX mice following a lesion to a peripheral nerve. The reduction in motor function in the crushed group compared with the control groups may reflect the cycles of muscle degeneration/regeneration that occur postnatally. Thus, G-CSF treatment increases motor function in MDX mice. Nevertheless, the decrease in baseline motor function in these mice is not reversed completely by G-CSF.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacología , Músculo Esquelético/efectos de los fármacos , Atrofia Muscular/tratamiento farmacológico , Regeneración Nerviosa/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Neuropatía Ciática/tratamiento farmacológico , Animales , Axones/efectos de los fármacos , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Marcha/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos mdx , Músculo Esquelético/lesiones , Músculo Esquelético/fisiología , Compresión Nerviosa , Recuperación de la Función/efectos de los fármacos , Nervio Ciático/lesiones , Nervio Ciático/fisiología , Resultado del Tratamiento
15.
PLoS One ; 9(8): e105740, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25153082

RESUMEN

Paraquat (PQ) is an agrochemical agent commonly used worldwide, which is allied to potential risks of intoxication. This herbicide induces the formation of reactive oxygen species (ROS) that ends up compromising various organs, particularly the lungs and the brain. This study evaluated the deleterious effects of paraquat on the central nervous system (CNS) and peripherally, with special attempts to assess the putative protective effects of the selective CXCR2 receptor antagonist SB225002 on these parameters. PQ-toxicity was induced in male Wistar rats, in a total dose of 50 mg/kg, and control animals received saline solution at the same schedule of administration. Separate groups of animals were treated with the selective CXCR2 antagonist SB225002 (1 or 3 mg/kg), administered 30 min before each paraquat injection. The major changes found in paraquat-treated animals were: decreased body weight and hypothermia, nociception behavior, impairment of locomotor and gait capabilities, enhanced TNF-α and IL-1ß expression in the striatum, and cell migration to the lungs and blood. Some of these parameters were reversed when the antagonist SB225002 was administered, including recovery of physiological parameters, decreased nociception, improvement of gait abnormalities, modulation of striatal TNF-α and IL-1ß expression, and decrease of neutrophil migration to the lungs and blood. Taken together, our results demonstrate that damage to the central and peripheral systems elicited by paraquat can be prevented by the pharmacological inhibition of CXCR2 chemokine receptors. The experimental evidence presented herein extends the comprehension on the toxicodynamic aspects of paraquat, and opens new avenues to treat intoxication induced by this herbicide.


Asunto(s)
Encéfalo/efectos de los fármacos , Herbicidas/farmacología , Paraquat/farmacología , Compuestos de Fenilurea/farmacología , Receptores de Interleucina-8B/antagonistas & inhibidores , Animales , Conducta Animal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Encéfalo/metabolismo , Movimiento Celular/efectos de los fármacos , Quimiocinas/metabolismo , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Marcha/efectos de los fármacos , Hipotermia/inducido químicamente , Hipotermia/metabolismo , Interleucina-1beta/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Receptores de Interleucina-8B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
16.
Arq Neuropsiquiatr ; 72(1): 28-32, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24637979

RESUMEN

UNLABELLED: The objective of this study was to evaluate the effects of botulinum toxin type A (BTX-A) on spastic foot in stroke patients in a rehabilitation program. METHOD: Hemiparetic stroke patients (n=21) enrolled in a rehabilitation program were divided into two groups. The first group (n=11) received a total of 300 UI BTX-A, and the second group (n=10) received 100 UI BTX-A. All patients were assessed at baseline and 2, 4, 8 and 12 weeks after injection for Modified Ashworth Score, time walking 10 meters, and the Functional Independence Measure (mFIM) motor score. RESULTS: The higher-dose group exhibited a significant improvement in spasticity, and both groups showed an improvement in time walking 10 meters and mFIM, with no significant differences between them. CONCLUSIONS: Our findings suggest that gains in gait velocity and functional independence were not correlated to BTX-A dose.


Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Enfermedades del Pie/tratamiento farmacológico , Fármacos Neuromusculares/uso terapéutico , Rehabilitación de Accidente Cerebrovascular , Actividades Cotidianas , Adulto , Femenino , Enfermedades del Pie/etiología , Marcha/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora/efectos de los fármacos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Espasticidad Muscular/fisiopatología , Estadísticas no Paramétricas , Accidente Cerebrovascular/complicaciones , Factores de Tiempo , Resultado del Tratamiento , Caminata/fisiología
17.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;72(1): 28-32, 01/2014. tab, graf
Artículo en Inglés | LILACS | ID: lil-697593

RESUMEN

The objective of this study was to evaluate the effects of botulinum toxin type A (BTX-A) on spastic foot in stroke patients in a rehabilitation program. Method: Hemiparetic stroke patients (n=21) enrolled in a rehabilitation program were divided into two groups. The first group (n=11) received a total of 300UI BTX-A, and the second group (n=10) received 100 UI BTX-A. All patients were assessed at baseline and 2, 4, 8 and 12 weeks after injection for Modified Ashworth Score, time walking 10 meters, and the Functional Independence Measure (mFIM) motor score. Results: The higher-dose group exhibited a significant improvement in spasticity, and both groups showed an improvement in time walking 10 meters and mFIM, with no significant differences between them. Conclusions: Our findings suggest that gains in gait velocity and functional independence were not correlated to BTX-A dose. .


O objetivo deste estudo foi avaliar os efeitos da toxina botulínica tipo A (TXB-A) sobre a espasticidade de membro inferior em pacientes pós-AVE em reabilitação. Método: 21 pacientes hemiparéticos foram divididos em dois grupos que receberam doses de TXB-A de 300UI (Grupo 1) e 100UI (Grupo 2) e foram avaliados antes da injeção e 2, 4, 8 e 12 semanas após, quanto à escala de Ashworth modificada, tempo para andar 10 metros e escore motor da Medida de Independência Funcional (MIFm). Resultados: O grupo que utilizou dose mais alta teve melhora significativa da espasticidade. Ambos os grupos tiveram melhora do tempo para andar 10 metros e da MIFm sem diferença significativa entre eles. Conclusões: A melhora da velocidade de marcha e da independência funcional não foram correlacionadas com a dose de TXB-A na amostra analisada. .


Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Toxinas Botulínicas Tipo A/uso terapéutico , Enfermedades del Pie/tratamiento farmacológico , Fármacos Neuromusculares/uso terapéutico , Accidente Cerebrovascular/rehabilitación , Actividades Cotidianas , Enfermedades del Pie/etiología , Marcha/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Espasticidad Muscular/fisiopatología , Estadísticas no Paramétricas , Accidente Cerebrovascular/complicaciones , Factores de Tiempo , Resultado del Tratamiento , Caminata/fisiología
18.
Arq Neuropsiquiatr ; 67(1): 62-8, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19330214

RESUMEN

We evaluated the safety and effectiveness of botulinum toxin A (BoNT/A) in the treatment of spasticity in 20 children with spastic diplegic cerebral palsy (CP). All the patients received injections in the gastrocnemius and soleus, and 15 received injections in the adductors. The total dose varied from 70 to 140 U (99.75+/-16.26 U), or 7.45+/-2.06 U/kg per patient. The treatment improved the patients' walking and gait pattern significantly. There was also a significant alteration in the heel-ground distance and increased motion of the ankle joint. These structural changes in the feet were sustained until the end of the follow-up, although the same was not observed for the functional parameters. Three patients complained of weakness in the lower limbs. In conclusion, BoNT/A is safe and effective when used in a single session of injections and produces a sustained structural modification of the lower limbs. However, functional changes are temporary and are only observed during the peak effect of the drug.


Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Parálisis Cerebral/tratamiento farmacológico , Fármacos Neuromusculares/administración & dosificación , Adolescente , Parálisis Cerebral/complicaciones , Niño , Preescolar , Femenino , Estudios de Seguimiento , Marcha/efectos de los fármacos , Humanos , Lactante , Extremidad Inferior/fisiopatología , Masculino , Espasticidad Muscular/tratamiento farmacológico , Tono Muscular/efectos de los fármacos , Estadísticas no Paramétricas , Resultado del Tratamiento
19.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;67(1): 62-68, Mar. 2009. graf, tab
Artículo en Inglés | LILACS | ID: lil-509110

RESUMEN

We evaluated the safety and effectiveness of botulinum toxin A (BoNT/A) in the treatment of spasticity in 20 children with spastic diplegic cerebral palsy (CP). All the patients received injections in the gastrocnemius and soleus, and 15 received injections in the adductors. The total dose varied from 70 to 140 U (99.75±16.26 U), or 7.45±2.06 U/kg per patient. The treatment improved the patients' walking and gait pattern significantly. There was also a significant alteration in the heel-ground distance and increased motion of the ankle joint. These structural changes in the feet were sustained until the end of the follow-up, although the same was not observed for the functional parameters. Three patients complained of weakness in the lower limbs. In conclusion, BoNT/A is safe and effective when used in a single session of injections and produces a sustained structural modification of the lower limbs. However, functional changes are temporary and are only observed during the peak effect of the drug.


Para avaliação da segurança e eficácia do tratamento com toxina botulínica A (TB-A) na espasticidade na paralisia cerebral (PC), foram selecionadas 20 crianças com a forma diplegia espástica. Todos os pacientes receberam injeções nos gastrocnêmios e sóleos, 15 receberam doses nos adutores da coxa. A dose total variou de 70 a 140 Us (99,75±16,26 U), 7,45±2,06 U/Kg por paciente. O tratamento com a TB-A melhorou significativamente a deambulação e o padrão de marcha. Houve também significativa alteração da distância tornozelo-solo e aumento da amplitude de movimento da articulação do tornozelo. Essas mudanças estruturais dos pés se mantiveram até o final do acompanhamento. O mesmo não foi observado com parâmetros funcionais. Três pacientes apresentaram fraqueza em membros inferiores. Conclui-se que a TB-A, em uma única aplicação, é segura e eficaz. Há modificação sustentada da estrutura motora dos membros inferiores, porém mudanças funcionais são temporárias, durante o pico de ação do medicamento.


Asunto(s)
Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Toxinas Botulínicas Tipo A/administración & dosificación , Parálisis Cerebral/tratamiento farmacológico , Fármacos Neuromusculares/administración & dosificación , Parálisis Cerebral/complicaciones , Estudios de Seguimiento , Marcha/efectos de los fármacos , Extremidad Inferior/fisiopatología , Espasticidad Muscular/tratamiento farmacológico , Tono Muscular/efectos de los fármacos , Estadísticas no Paramétricas , Resultado del Tratamiento
20.
J Neurosci Methods ; 177(2): 317-21, 2009 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-19026686

RESUMEN

The administration of 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway is a rat model of Parkinson's disease (PD). The footfault test is a behavioural task in which rodents have their motor functions assessed. Here, we observed that unilaterally 6-OHDA-lesioned animals show a context-induced ipsilateral rotational behaviour when placed on the footfault apparatus for 3 min and this may be used as index to detect lesioned animals. Our results showed a sensitivity and specificity of 100% for lesions higher than 94% and 64%, respectively (ROC curve: AUC=0.988). A binary logistic regression model showed an expB=1.116 (95% CI, 1.007-1.236) and C=-9.081+/-4.554 (p=0.046) using the nigral tyrosine hidroxylase immunocontent as standard (each unit represents a 10%-lesion extension). Additionally, the footfault test was more sensitive than apomorphine challenging at 1mg/kg when these tests were carried out days apart and it was less sensitive than methylphenidate at 40 mg/kg (sign test, p<0.05). Therefore, the footfault test may be very useful in the PD animal model for screening animals since it is fast and simple and it does not require a drug to induce rotational activity.


Asunto(s)
Ciencias de la Conducta/métodos , Neurofarmacología/métodos , Oxidopamina/toxicidad , Trastornos Parkinsonianos/diagnóstico , Trastornos Parkinsonianos/fisiopatología , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Ciencias de la Conducta/instrumentación , Modelos Animales de Enfermedad , Dopamina/biosíntesis , Agonistas de Dopamina/farmacología , Evaluación Preclínica de Medicamentos/instrumentación , Evaluación Preclínica de Medicamentos/métodos , Marcha/efectos de los fármacos , Marcha/fisiología , Trastornos Neurológicos de la Marcha/inducido químicamente , Trastornos Neurológicos de la Marcha/diagnóstico , Trastornos Neurológicos de la Marcha/fisiopatología , Masculino , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/enzimología , Degeneración Nerviosa/patología , Neuronas/efectos de los fármacos , Neuronas/enzimología , Neuronas/patología , Neurofarmacología/instrumentación , Trastornos Parkinsonianos/inducido químicamente , Ratas , Ratas Wistar , Sustancia Negra/efectos de los fármacos , Sustancia Negra/enzimología , Sustancia Negra/patología , Simpaticolíticos/toxicidad , Tirosina 3-Monooxigenasa/efectos de los fármacos , Tirosina 3-Monooxigenasa/metabolismo
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