1 Department of Clinical Medicine - The Department of Neurosurgery, Department of Clinical Medicine, Health, Aarhus University2 Department of Clinical Medicine - Electron Microscopy Laboratory, Department of Clinical Medicine, Health, Aarhus University3 Stereological Research Laboratory, Faculty of Health Sciences, Aarhus University, Aarhus University4 NeuroCluster5 Department of Biological Sciences, Zoophysiology, Faculty of Science, Aarhus University, Aarhus University6 Department of Clinical Medicine - Stereological Research Laboratory, Department of Clinical Medicine, Health, Aarhus University7 Institut for Neurovidenskab og Farmakologi8 Department of Clinical Medicine - The Department of Neurosurgery, Department of Clinical Medicine, Health, Aarhus University9 Department of Clinical Medicine - Stereological Research Laboratory, Department of Clinical Medicine, Health, Aarhus University
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.
Experimental and Translational Stroke Medicine, 2012, Vol 4, Issue 1