Reduced infarct size in neuroglobin-null mice after experimental stroke in vivo

Experimental & Translational Stroke Medicine

Anders Hay-Schmidt¹  Jens Randel Nyengaard³  Jesper Kelsen²  Christian Ansgar Hundahl⁴  Zindy Raida⁵ 

[1] The Panum Institute; Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark;Department of Neurosurgery, University Hospital Copenhagen (Rigshospitalet), Copenhagen, Denmark;Stereology and Electron Microscopy Research Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark;Department of Clinical Biochemistry, University Hospital Bispebjerg, Copenhagen, Denmark;Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

关键词: Brain;    Immunohistochemistry;    Ischemia;    Knock out;    Neuroglobin;   

Others  :  861821
DOI  :  10.1186/2040-7378-4-15

 received in 2012-05-10, accepted in 2012-07-11,  发布年份 2012

【 摘 要 】

Background

Neuroglobin is considered to be a novel important pharmacological target in combating stroke and neurodegenerative disorders, although the mechanism by which this protection is accomplished remains an enigma. We hypothesized that if neuroglobin is directly involved in neuroprotection, then permanent cerebral ischemia would lead to larger infarct volumes in neuroglobin-null mice than in wild-type mice.

Methods

Using neuroglobin-null mice, we estimated the infarct volume 24 hours after permanent middle cerebral artery occlusion using Cavalieri’s Principle, and compared the infarct volume in neuroglobin-null and wild-type mice. Neuroglobin antibody staining was used to examine neuroglobin expression in the infarct area of wild-type mice.

Results

Infarct volumes 24 hours after permanent middle cerebral artery occlusion were significantly smaller in neuroglobin-null mice than in wild-types (p < 0.01). Neuroglobin immunostaining of the penumbra area revealed no visible up-regulation of neuroglobin protein in ischemic wild-type mice when compared to uninjured wild-type mice. In uninjured wild-type mice, neuroglobin protein was seen throughout cortical layer II and sparsely in layer V. In contrast, no neuroglobin-immunoreactive neurons were observed in the aforementioned layers of the ischemia injured cortical area, or in the surrounding penumbra of ischemic wild-type mice. This suggests no selective sparing of neuroglobin expressing neurons in ischemia.

Conclusions

Neuroglobin-deficiency resulted in reduced tissue infarction, suggesting that, at least at endogenous expression levels, neuroglobin in itself is non-protective against ischemic injury.

【 授权许可】

   
2012 Raida et al.; licensee BioMed Central Ltd.

【 图 表 】

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