Evaluation of long-term upregulation of Calbindin D28K as a preventive approach for ischaemic stroke

International Journal of Stroke : Official Journal of the International Stroke Society
Florian B FreimannSebastian Kügler

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.

References

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Dec 25, 2003·Cerebrovascular Diseases·Nils Gunnar Wahlgren, Niaz Ahmed
Dec 8, 2004·Biochemical and Biophysical Research Communications·Uwe MichelSebastian Kügler
May 20, 2006·Cellular and Molecular Neurobiology·Konstantin-Alexander Hossmann
Jul 27, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yongfeng FanChuan-Zhen Lu

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Citations

Jun 24, 2017·Journal of Cellular and Molecular Medicine·Marilena GregoriniTeresa Rampino
Jun 3, 2014·Acta Neuropathologica Communications·Prabhu Ramamoorthy, Honglian Shi
Sep 12, 2018·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Shuji IritaniNorio Ozaki
Jul 13, 2011·Journal of Aging Research·Dori E RosenbergBasia Belza

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