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Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes.
Kelly-Cobbs, Aisha I; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H; Ogbi, Safia N; Fagan, Susan C; Ergul, Adviye.
Afiliación
  • Kelly-Cobbs AI; Department of Physiology, Georgia Regents University Augusta, Augusta, GA 30912, USA.
Am J Physiol Heart Circ Physiol ; 304(6): H806-15, 2013 Mar 15.
Article en En | MEDLINE | ID: mdl-23335797
Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fármacos Neuroprotectores / Infarto de la Arteria Cerebral Media / Curcumina / Diabetes Mellitus Tipo 2 / Inhibidores de la Metaloproteinasa de la Matriz / Metaloporfirinas / Minociclina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Am J Physiol Heart Circ Physiol Asunto de la revista: CARDIOLOGIA / FISIOLOGIA Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fármacos Neuroprotectores / Infarto de la Arteria Cerebral Media / Curcumina / Diabetes Mellitus Tipo 2 / Inhibidores de la Metaloproteinasa de la Matriz / Metaloporfirinas / Minociclina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Am J Physiol Heart Circ Physiol Asunto de la revista: CARDIOLOGIA / FISIOLOGIA Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos