Aims: 

The purpose of study is to evaluate the effect of simvastatin on ischemic brain injury. A variety of endoplasmic reticulum (ER) stresses trigger the unfolded protein response (UPR), a compensatory response whose most proximal sensors are the ER membrane bound proteins IRE1 and ATF6.

Methods: 

We have simultaneously examined the activation of ATF6, IRE1, Grp78 and Xbp-1 at mRNA and protein levels after 15 minutes 4-VO ischemia and different times of reperfusion (1, 3 and 24h). We used Western blot with immunodetection to determine protein levels and RT-PCR to determine mRNA levels.

Results: 

The results showed that simvastatin increased ATF6 mRNA levels and caused significant difference at I stage between treated and untreated animals. In simvastatin treated animals it follows normal ischemic behaviour of mRNA levels; however the response at R24 is not so sharp. Our results for Grp78 detect the highest mRNA level in 3h of reperfusion in cortex. In addition to this we observed increased mRNA level after simvastatin treatment. Results also showed that statins kept increasing level of mRNA between R3 and R24 in treated animals. Simvastatin lightly decreased mRNA level for Xbp1 during ischemia and 1h reperfusion. Protective effect is visible mainly in 24h of reperfusion. mRNA level of untreated animals showed no significant shift between 1 and 24h of reperfusion.

Conclusion: 

These data indicates that statins, in addition to their cholesterol lowering effect, might exert a neuroprotective role in the attenuation of ER stress response after acute stroke/reperfusion.

This work was supported by VEGA 3380/06, Grants of COST B30 and UK/70/07.