RESUMEN
PURPOSE: To investigate the effects of aquaporin 4 (AQP4) and inward rectifier potassium channel 4.1 (Kir4.1) on medullospinal edema after treatment with methylprednisolone (MP) to suppress acute spinal cord injury (ASCI) in rats. METHODS: Sprague Dawley rats were randomly divided into control, sham, ASCI, and MP-treated ASCI groups. After the induction of ASCI, we injected 30 mg/kg MP via the tail vein at various time points. The Tarlov scoring method was applied to evaluate neurological symptoms, and the wet-dry weights method was applied to measure the water content of the spinal cord. RESULTS: The motor function score of the ASCI group was significantly lower than that of the sham group, and the spinal water content was significantly increased. In addition, the levels of AQP4 and Kir4.1 were significantly increased, as was their degree of coexpression. Compared with that in the ASCI group, the motor function score and the water content were significantly increased in the MP group; in addition, the expression and coexpression of AQP4 and Kir4.1 were significantly reduced. CONCLUSION: Methylprednisolone inhibited medullospinal edema in rats with acute spinal cord injury, possibly by reducing the coexpression of aquaporin 4 and Kir4.1 in medullospinal tissues.
Asunto(s)
Acuaporina 4/metabolismo , Edema/tratamiento farmacológico , Glucocorticoides/farmacología , Metilprednisolona/farmacología , Canales de Potasio de Rectificación Interna/metabolismo , Enfermedades de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Enfermedad Aguda , Animales , Acuaporina 4/uso terapéutico , Modelos Animales de Enfermedad , Edema/metabolismo , Técnica del Anticuerpo Fluorescente , Glucocorticoides/uso terapéutico , Masculino , Metilprednisolona/uso terapéutico , Canales de Potasio de Rectificación Interna/uso terapéutico , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Médula Espinal/citología , Médula Espinal/efectos de los fármacos , Enfermedades de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/inducido químicamenteRESUMEN
Abstract Purpose: To investigate the effects of aquaporin 4 (AQP4) and inward rectifier potassium channel 4.1 (Kir4.1) on medullospinal edema after treatment with methylprednisolone (MP) to suppress acute spinal cord injury (ASCI) in rats. Methods: Sprague Dawley rats were randomly divided into control, sham, ASCI, and MP-treated ASCI groups. After the induction of ASCI, we injected 30 mg/kg MP via the tail vein at various time points. The Tarlov scoring method was applied to evaluate neurological symptoms, and the wet-dry weights method was applied to measure the water content of the spinal cord. Results: The motor function score of the ASCI group was significantly lower than that of the sham group, and the spinal water content was significantly increased. In addition, the levels of AQP4 and Kir4.1 were significantly increased, as was their degree of coexpression. Compared with that in the ASCI group, the motor function score and the water content were significantly increased in the MP group; in addition, the expression and coexpression of AQP4 and Kir4.1 were significantly reduced. Conclusion: Methylprednisolone inhibited medullospinal edema in rats with acute spinal cord injury, possibly by reducing the coexpression of aquaporin 4 and Kir4.1 in medullospinal tissues.
Asunto(s)
Animales , Masculino , Ratas , Enfermedades de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Metilprednisolona/farmacología , Canales de Potasio de Rectificación Interna/metabolismo , Edema/tratamiento farmacológico , Acuaporina 4/metabolismo , Glucocorticoides/farmacología , Médula Espinal/citología , Médula Espinal/efectos de los fármacos , Enfermedades de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/inducido químicamente , Metilprednisolona/uso terapéutico , Distribución Aleatoria , Enfermedad Aguda , Técnica del Anticuerpo Fluorescente , Ratas Sprague-Dawley , Canales de Potasio de Rectificación Interna/uso terapéutico , Modelos Animales de Enfermedad , Edema/metabolismo , Acuaporina 4/uso terapéutico , Glucocorticoides/uso terapéuticoRESUMEN
Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS), and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.