Brain proteomics identifies potential simvastatin targets in acute phase of stroke in a rat embolic model
Article first published online: 30 APR 2014
© 2014 International Society for Neurochemistry
Journal of Neurochemistry
Volume 130, Issue 2, pages 301–312, July 2014
How to Cite
J. Neurochem. (2014) 130, 301–312.
- Issue published online: 7 JUL 2014
- Article first published online: 30 APR 2014
- Accepted manuscript online: 24 MAR 2014 12:02PM EST
- Manuscript Accepted: 18 MAR 2014
- Manuscript Revised: 12 MAR 2014
- Manuscript Received: 15 DEC 2013
- Instituto de Salud Carlos III from the Spanish Ministry of Economy. Grant Numbers: FI10/00508, CP12/03259, CP09/00265
- European Union's Seventh Framework Programme. Grant Numbers: FP7/2007-2013, 201024, 202213
- Neurovascular Research Laboratory. Grant Number: RD12/0014/0005
- . Grant Numbers: FIS 11/0176, EC07/90195
- European Stroke Network
- acute phase treatment;
- embolic cerebral ischemia;
Finding an efficient neuroprotectant is of urgent need in the field of stroke research. The goal of this study was to test the effect of acute simvastatin administration after stroke in a rat embolic model and to explore its mechanism of action through brain proteomics. To that end, male Wistar rats were subjected to a Middle Cerebral Arteria Occlusion and simvastatin (20 mg/kg s.c) (n = 11) or vehicle (n = 9) were administered 15 min after. To evaluate the neuroprotective mechanisms of simvastatin, brain homogenates after 48 h were analyzed by two-dimensional fluorescence Difference in Gel Electrophoresis (DIGE) technology. We confirmed that simvastatin reduced the infarct volume and improved neurological impairment at 48 h after the stroke in this model. Considering our proteomics analysis, 66 spots, which revealed significant differences between groups, were analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry allowing the identification of 27 proteins. From these results, we suggest that simvastatin protective effect can be partly explained by the attenuation of the oxidative and stress response at blood–brain barrier level after cerebral ischemia. Interestingly, analyzing one of the proteins (HSP75) in plasma from stroke patients who had received simvastatin during the acute phase, we confirmed the results found in the pre-clinical model.
Our aim was to study statins benefits when administered during the acute phase of stroke and to explore its mechanisms of action through brain proteomics assay. Using an embolic model, simvastatin-treated rats showed significant infarct volume reduction and neurological improvement compared to vehicle-treated group. Analyzing their homogenated brains by two-dimensional fluorescence Difference in Gel Electrophoresis (DIGE) technology, we concluded that the protective effect of simvastatin can be attributable to oxidative stress response attenuation and blood–brain barrier protection after cerebral ischemia.