title: Evaluation of long-term upregulation of Calbindin D28K as a preventive approach for ischaemic stroke.
abstract: Buffering of intracellular calcium peaks following an acute ischaemic stroke protects neurons from necrotic and apoptotic cell death. However, the need for on-demand delivery of protective agents due to the short therapeutic window in stroke therapy makes it difficult to apply a calcium-buffering strategy in patients. We investigated the effects of a preventive upregulation of the calcium-binding protein Calbindin D28K as a potential approach for patients at a high risk of ischaemic stroke. We overexpressed Calbindin D28K in the striatal and cortical region in mice using an adeno-associated viral vector (AAV) for 12 weeks, and then assessed neuroprotective effects after MCAO. In contrast to studies showing a neuroprotective effect of shortly induced Calbindin D28K overexpression, we found no increased survival of neurons overexpressing Calbindin D28K for 12 weeks.We suggest that neuronal calcium metabolism adapts to higher Calbindin D28K levels after long-term overexpression. This potentially preventive approach to protect from ischaemic stroke does not have clinical applicability.
authors.affiliation: Department of Neurology, Medical School, University of Göttingen, Göttingen, Germany.
authors.forename: Florian B
authors.initials: FB
authors.lastname: Freimann
authors.forename: Olaf
authors.initials: O
authors.lastname: Crome
authors.forename: Zinayida
authors.initials: Z
authors.lastname: Shevtsova
authors.forename: Mathias
authors.initials: M
authors.lastname: Bähr
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kügler
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology / Q000517:prevention & control*; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D000229:Dependovirus; D005456:Fluorescent Dyes; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D009336:Necrosis; D017072:Neostriatum / Q000378:metabolism; D012306:Risk; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis*; D020521:Stroke / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D015854:Up-Regulation
chemical_list: C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D005456:Fluorescent Dyes; D064030:S100 Calcium Binding Protein G; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D002118:Calcium