Résumé
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.
Sujets)
Animaux , Mâle , Rats , Maladies de la moelle épinière/traitement médicamenteux , Traumatismes de la moelle épinière/traitement médicamenteux , Méthylprednisolone/pharmacologie , Canaux potassiques rectifiants entrants/métabolisme , Oedème/traitement médicamenteux , Aquaporine-4/métabolisme , Glucocorticoïdes/pharmacologie , Moelle spinale/cytologie , Moelle spinale/effets des médicaments et des substances chimiques , Maladies de la moelle épinière/métabolisme , Traumatismes de la moelle épinière/induit chimiquement , Méthylprednisolone/usage thérapeutique , Répartition aléatoire , Maladie aigüe , Technique d'immunofluorescence , Rat Sprague-Dawley , Canaux potassiques rectifiants entrants/usage thérapeutique , Modèles animaux de maladie humaine , Oedème/métabolisme , Aquaporine-4/usage thérapeutique , Glucocorticoïdes/usage thérapeutiqueRésumé
O diabetes neonatal (DN) é uma condição rara caracterizada por hiperglicemia, que necessita de tratamento com insulina, diagnosticado nos primeiros meses de vida. Clinicamente pode ser classificado em DN transitório quando ocorre remissão da doença em poucos meses, podendo haver recorrência posterior; ou permanente quando, como o nome indica, não ocorre remissão. Ambas as condições são geneticamente heterogêneas; entretanto a maioria dos casos de DN transitório é decorrente de anormalidades da região de imprinted no cromossomo 6q24. Mutações ativadoras em heterozigose no gene KCNJ11, que codifica a subunidade Kir6.2 do canal de potássio ATP-sensível, são a causa mais comum de DN permanente. No presente artigo, discutimos as características clínicas do DN, os mecanismos moleculares envolvidos e suas implicações terapêuticas.
Neonatal diabetes is a rare condition characterized by hyperglycemia, requiring insulin treatment, diagnosed within the first months of life. The disorder may be either transient, resolving in infancy or early childhood with possible relapse later, or permanent in which case lifelong treatment is necessary. Both conditions are genetically heterogeneous; however, the majority of the cases of transient neonatal diabetes are due to abnormalities of an imprinted region of chromosome 6q24. For permanent neonatal diabetes, the most common causes are heterozygous activating mutations of KCNJ11, the gene encoding the Kir6.2 sub-unit of the ATP-sensitive potassium channel. In this article we discuss the clinical features of neonatal diabetes, the underlying genetic defects and the therapeutic implications.