RESUMO
In addition to classic motor symptoms, Parkinson's disease (PD) is characterized by cognitive and emotional deficits, which have been demonstrated to precede motor impairments. The present study addresses the question of whether a partial degeneration of dopaminergic neurons using 6-hydroxydopamine (6-OHDA) in rats is able to induce premotor behavioral signs. The time-course of nigrostriatal damage was evaluated by tyrosine hydroxylase immunohistochemistry and the levels of dopamine, noradrenaline, and 5-HT in various brain regions were analyzed by high performance liquid chromatography (HPLC). Behavioral tests that assessed a variety of psychological functions, including locomotor activity, emotional reactivity and depression, anxiety and memory were conducted on 6-OHDA lesioned rats. Bilateral infusion of 6-OHDA in the striatum of rats caused early (1 week) damage of dopaminergic terminals in striatum and in cell bodies in substantia nigra pars compacta. The nigrostriatal lesion was accompanied by early loss of dopamine in the striatum, which remained stable through a 3-week period of observation. In addition, a late (3 weeks) loss of dopamine in the prefrontal cortex, but not in the hippocampus, was seen. Additional noradrenergic and serotonergic alterations were observed after 6-OHDA administration. The results indicated that 6-OHDA lesioned rats show decreased sucrose consumption and an increased immobility time in the forced swimming test, an anhedonic-depressive-like effect. In addition, an anxiogenic-like activity in the elevated plus maze test and cognitive impairments were observed on the cued version of the Morris water maze and social recognition tests. These findings suggest that partial striatal dopaminergic degeneration and parallel dopaminergic, noradrenergic and serotonergic alterations in striatum and prefrontal cortex may have caused the emotional and cognitive deficits observed in this rat model of early phase PD.
Assuntos
Sintomas Afetivos/etiologia , Química Encefálica/fisiologia , Transtornos Cognitivos/etiologia , Doença de Parkinson/complicações , Doença de Parkinson/metabolismo , Adrenérgicos/toxicidade , Análise de Variância , Animais , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/patologia , Química Encefálica/efeitos dos fármacos , Modelos Animais de Doenças , Preferências Alimentares/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Oxidopamina/toxicidade , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Reconhecimento Psicológico/efeitos dos fármacos , Reconhecimento Psicológico/fisiologia , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
The rat models currently employed for studies of nerve regeneration present distinct disadvantages. We propose a new technique of stretch-induced nerve injury, used here to evaluate the influence of gabapentin (GBP) on nerve regeneration. Male Wistar rats (300 g; n=36) underwent surgery and exposure of the median nerve in the right forelimbs, either with or without nerve injury. The technique was performed using distal and proximal clamps separated by a distance of 2 cm and a sliding distance of 3 mm. The nerve was compressed and stretched for 5 s until the bands of Fontana disappeared. The animals were evaluated in relation to functional, biochemical and histological parameters. Stretching of the median nerve led to complete loss of motor function up to 12 days after the lesion (P<0.001), compared to non-injured nerves, as assessed in the grasping test. Grasping force in the nerve-injured animals did not return to control values up to 30 days after surgery (P<0.05). Nerve injury also caused an increase in the time of sensory recovery, as well as in the electrical and mechanical stimulation tests. Treatment of the animals with GBP promoted an improvement in the morphometric analysis of median nerve cross-sections compared with the operated vehicle group, as observed in the area of myelinated fibers or connective tissue (P<0.001), in the density of myelinated fibers/mm2 (P<0.05) and in the degeneration fragments (P<0.01). Stretch-induced nerve injury seems to be a simple and relevant model for evaluating nerve regeneration.
RESUMO
BACKGROUND: Neuropathic pain is severely debilitating and resistant to pharmacological approaches; therefore, the study of therapies to complement its treatment is especially relevant. In a case report study, light-emitting diode therapy (LEDT) has shown analgesic activity as well as reduced the expression of pro-inflammatory cytokines in a rabbit osteoarthritis model and in calcaneal tendinitis in rats. Although LEDT stimulated morphofunctional recovery after nerve injury in rats, its effect against neuropathic pain has not been tested. METHODS: To that purpose, mice under anaesthesia were subjected to the sciatic nerve crush (SNC) model. On the seventh post-operative day, after determining analgesic dose (energy density in joules), LEDT (950 nm, 80 mW/cm2, 2.5 J/cm2 ) was irradiated, daily for a period of 15 days, on the skin over the crush site. RESULTS: Compared with the SNC group, LEDT reduced mechanical hypersensitivity but not cold hypersensitivity which is induced by SNC, decreased spinal cord and sciatic nerve levels of tumour necrosis factor alpha (TNF-α) but did not alter interleukin (IL)-1ß and IL-10 levels, and finally, failed to accelerate motor functional recovery and morphological nerve regeneration. CONCLUSION: Taken together, these data provide first-hand evidence of LEDT effectiveness against neuropathic pain induced by SNC, with corresponding decrease of pro-inflammatory cytokine levels, both in the sciatic nerve and in the spinal cord, although at a small analgesic dose, LEDT failed to accelerate nerve regeneration.
Assuntos
Analgésicos/uso terapêutico , Lasers Semicondutores/uso terapêutico , Dor/tratamento farmacológico , Nervo Isquiático/lesões , Medula Espinal/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Regeneração Nervosa/fisiologia , Dor/metabolismo , Dor/fisiopatologia , Manejo da Dor/métodos , Recuperação de Função Fisiológica/fisiologia , Nervo Isquiático/fisiopatologia , Nervo Isquiático/cirurgia , Medula Espinal/fisiopatologiaRESUMO
The rat models currently employed for studies of nerve regeneration present distinct disadvantages. We propose a new technique of stretch-induced nerve injury, used here to evaluate the influence of gabapentin (GBP) on nerve regeneration. Male Wistar rats (300 g; n=36) underwent surgery and exposure of the median nerve in the right forelimbs, either with or without nerve injury. The technique was performed using distal and proximal clamps separated by a distance of 2 cm and a sliding distance of 3 mm. The nerve was compressed and stretched for 5 s until the bands of Fontana disappeared. The animals were evaluated in relation to functional, biochemical and histological parameters. Stretching of the median nerve led to complete loss of motor function up to 12 days after the lesion (P<0.001), compared to non-injured nerves, as assessed in the grasping test. Grasping force in the nerve-injured animals did not return to control values up to 30 days after surgery (P<0.05). Nerve injury also caused an increase in the time of sensory recovery, as well as in the electrical and mechanical stimulation tests. Treatment of the animals with GBP promoted an improvement in the morphometric analysis of median nerve cross-sections compared with the operated vehicle group, as observed in the area of myelinated fibers or connective tissue (P<0.001), in the density of myelinated fibers/mm2 (P<0.05) and in the degeneration fragments (P<0.01). Stretch-induced nerve injury seems to be a simple and relevant model for evaluating nerve regeneration.