A new concept affecting restoration of inflammation-reactive astrocytes.

Block, L; Björklund, U; Westerlund, A; Jörneberg, P; Biber, B; Hansson, E

Block, L; Björklund, U; Westerlund, A; Jörneberg, P; Biber, B; Hansson, E.

Afiliación

Block L; Department of Anaesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, SE 413 45 Gothenburg, Sweden.

Neuroscience ; 250: 536-45, 2013 Oct 10.

Article en En | MEDLINE | ID: mdl-23892009

RESUMEN

Long-lasting pain may partly be a consequence of ongoing neuroinflammation, in which astrocytes play a significant role. Following noxious stimuli, increased inflammatory receptor activity, influences in Na(+)/K(+)-ATPase activity and actin filament organization occur within the central nervous system. In astrocytes, the Ca(2+) signaling system, Na(+) transporters, cytoskeleton, and release of pro-inflammatory cytokines change during inflammation. The aim of this study was to restore these cell parameters in inflammation-reactive astrocytes. We found that the combination of (1) endomorphin-1, an opioid agonist that stimulates the Gi/o protein of the µ-opioid receptor; (2) naloxone, an opioid antagonist that inhibits the Gs protein of the µ-opioid receptor at ultralow concentrations; and (3) levetiracetam, an anti-epileptic agent that counteracts the release of IL-1ß, managed to activate the Gi/o protein and Na(+)/K(+)-ATPase activity, inhibit the Gs protein, and decrease the release of IL-1ß. The cell functions of astrocytes in an inflammatory state were virtually restored to their normal non-inflammatory state and it could be of clinical significance and may be useful for the treatment of long-term pain.

Asunto(s)

Astrocitos/fisiología; Inflamación/patología; Actinas/metabolismo; Analgésicos Opioides/farmacología; Animales; Señalización del Calcio/efectos de los fármacos; Capilares/metabolismo; Técnicas de Cocultivo; Citocinas/metabolismo; Citoesqueleto/efectos de los fármacos; Citoesqueleto/fisiología; Células Endoteliales/metabolismo; Ácido Glutámico/farmacología; Interleucina-1beta/metabolismo; Levetiracetam; Lipopolisacáridos/farmacología; Masculino; Naloxona/farmacología; Antagonistas de Narcóticos/farmacología; Nootrópicos/farmacología; Oligopéptidos/farmacología; Piracetam/análogos & derivados; Piracetam/farmacología; Cultivo Primario de Células; Ratas; Ratas Sprague-Dawley; ATPasa Intercambiadora de Sodio-Potasio/metabolismo

Palabras clave

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; ANOVA; AUC; BSA; ELISA; GFAP; HEPES; HHBSS; Hank's HEPES-buffered saline solution; IL-ß release; LPS; MEM; PAGE; PBS; SDS; Sap; TBST; TLR4; Toll-like receptor 4; Tris-buffered saline; analysis of variance; areas under the curve; astrocyte networks; bovine serum albumin; enzyme-linked immunosorbent assay; glial fibrillary acidic protein; levetiracetam; lipopolysaccharide; minimum essential medium; phosphate-buffered saline; polyacrylamide gel electrophoresis; saponine; sodium dodecyl sulfate; µ-opioid agonist; µ-opioid antagonist; µ-opioid receptor

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Astrocitos / Inflamación Límite: Animals Idioma: En Revista: Neuroscience Año: 2013 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos

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