No abstract

Ischemic stroke remains a leading cause of death and disability around the world, with limited successful therapeutic strategies 1 . In the past decade, preventing neuronal damage to improve recovery has always been a focus in stroke research, which is still a promising target 2 . With regard to the major mechanisms of ischemic neuronal damage, early events such as oxidative stress, calcium overload, as well as excitotoxity, may rapidly result in neuronal necrosis in the infarct core; however, later events such as inflammation are relevant to programmed cell death in the penumbra 3 .Apoptosis is a classic type I programmed cell death. Accompanied by the activation of caspases, the induction of ABSTRACT: Background: Hypoxia inducible factor 1 (HIF-1) is a key transcriptional factor activated during cerebral ischemia, which regulates a great number of downstream genes, including those associated with cell death. In the present study, we aimed to test the hypothesis that post-ischemic HIF-1α up-regulation might promote autophagy activation; thereby, HIF-1α inhibitor 2ME2 might prevent neurons from ischemic injury through inhibiting autophagy. Methods: Global ischemia was induced using the four-vessel occlusion model (4-VO) in Sprague-Dawley rats (male, 250-280g). 2-Methoxyestradiol (2ME2, 5mg/kg, i.p.) was administrated to down-regulate HIF-1α expression. Post-ischemic beclin-1 and LC3 protein expression was determined at different time points through Western blot assay. Neuronal injury was determined by cresyl violet staining and TUNEL staining in coronal histological sections. Results:The expression of beclin-1 and the ratio of LC3-II/LC3-I increased significantly at 12 and 24 h after ischemia. 2ME2 could remarkably inhibit the up-regulation of beclin-1 and the increase of LC3-II/LC3-I ratio during reperfusion. Moreover, 2ME2 and 3-MA exhibited powerful protective effects against ischemic/reperfusion induced neuronal injury. Conclusions: This study confirmed that autophagy participated in post-ischemic neuronal injury. 2ME2, a HIF-1α inhibitor, might significantly decrease autophagy activation after cerebral ischemia and relieve post-ischemic neuronal injury. Our findings demonstrate that autophagy could be a potential target for neuronal protection after cerebral ischemia.RÉSUMÉ: Le 2-méthoxyestradiol atténue l'activation de l'autophagie après une ischémie globale : Contexte : Le facteur 1 induit par l'hypoxie (HIF-1) est un facteur transcriptionnel clé qui est activé pendant l'ischémie cérébrale et qui régule plusieurs gènes sous son contrôle, dont ceux qui sont associés à la mort cellulaire. Le but de cette étude était de vérifier l'hypothèse selon laquelle la régulation à la hausse de HIF-1α post-ischémique pourrait promouvoir l'activation de l'autophagie. Le 2-méthoxyestradiol (2ME2), un inhibiteur de HIF-1α, pourrait donc protéger les neurones du dommage ischémique en inhibant l'autophagie. Méthode : Nous avons induit une ischémie globale au moyen du modèle d'occlusion de quatre vaisseaux (4-VO) chez des ra...

Hemiballism-hemichorea (HB-HC) is commonly used to describe the basal ganglion dysfunction in non-ketotic hyperglycemic elderly patients. Here we report two elderly female patients with acute onset of involuntary movements induced by hyperglycemia with positive urine ketones. We described the computed tomography and magnetic resonance imaging findings in these two patients, which is similar to that of non-ketotic hyperglycemic HB-HC patients. FDG-PET was performed and the glucose metabolism in the corresponding lesion in these two patients was contradictory with each other. We tried to clarify the underlying mechanisms of HB-HC and explain the contradictory neuroradiological findings in FDG-PET as being performed at different clinical stages.