Do Statins Influence the Activity of c-fos Gene Following Transient Forebrain Ischaemia in the Adult Rat Hippocampus?

Abstract

Halašová E., A. Drgová, T. Matáková, Z. Tatarková The 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors (statins) have been associated with stroke prevention. This stroke prevention appears to occur apart from cholesterol lowering effects. a number of mechanisms have been postulated for this prevention. The aim of our study was to investigate the effect of simvastatin on the c-fos gene activity and its relation to delayed neuronal death in Ca1 region of hippocampus following transient forebrain ischemia in the adult rat hippocampus.a total of 17 male Wistar albino rats were used in this study. The animals were divided into three groups: 5 sham-operated animals; 6 ischemised rats without statin pre-treatment and 6 ischemised rats with statin pre-treatment. We used simvastatin at the dose of 20 mg/kg during 14 days prior to the ischemic attack. Fifteen min long transient forebrain ischemia was induced by the four-vessel occlusion. Two and a half h reperfusion was used for the c-Fos activity detection using immunostaining and 72 h reperfusion was used for the determination of neurons surviving using haematoxylin/eosin staining.The average neuronal density in the Ca1 region of hippocampus in the sham-operated rats, in ischemised rats without pre-treatment and in ischemised rats with statin pre-treatment was 47.03 ± 3.09/0,025 mm 2 , 9.05 ± 2.46/0,025 mm 2 and 16.45 ± 2.78/025 mm 2 , respectively. A significant neuroprotective effect was observed in the pre-treated ischemic group (P < 0.001) in comparison to the ischemic group without pre-treatment.The average of c-Fos positive nuclei density in the Ca1 region of hippocampus in the shamoperated rats, in ischemised rats without pre-treatment and in ischemised rats with statin pre-treatment was 0.266 ± 0.074/025 mm 2 , 28.2 ± 2.053/025 mm 2 , 30.3 ± 4.816/025 mm 2 , respectively. a highly significant difference in c-Fos positivity (P < 0.001) was found between the sham operated group and both ischemic groups (with and without pre-treatment). No significant difference in c-Fos positivity was observed between untreated ischemic and pre-treated ischemic groups (P > 0.05).These findings indicate that simvastatin provides protection against CA1 hypoxic neuronal injury, which is independent of c-fos activation. We can conclude that simvastatin neuroprotection may be mediated by multiple mechanisms as can be expected based on its pleiotropic effects. Simvastatin, cerebral ischemia, CA1 hippocampal region, c-Fos