Beckground and aims: Ischemic preconditioning (IPC) is a phenomenon whereby an organ's adaptive transient resistance to a lethal insult occurs by preconditioning this organ with a sublethal/mild insult of short duration. Recently, using an in vitro model of cerebral ischemia we demonstrated that resveratrol mimics IPC via the SIRT1 (a member of Sirtuin proteins family) pathway . In the present study we tested the hypothesis that tolerance for ischemia can be induced in brain by resveratrol pre-treatment. Methods: We compared efficacy of resveratrol preconditioning with IPC in protecting CA1 hippocampal neurons in a rat model of asphyxial cardiac arrest (CA). IPC was induced by tightening the carotid ligatures bilaterally following hypotension (50 mmHg) for 2 min . Resveratrol preconditioning was induced by injecting resveratrol (i.p.) at 10, 50 and 100 mg/kg dose. Eight minutes of CA was induced 48 h after IPC or resveratrol injection as described earlier . At the end of 7 days of resuscitation, the brain sections were examined for histopathological changes. The numbers of normal neurons were counted in CA1 hippocampus at 3.8 mm posterior to bregma. Results were expressed, as mean ± SD. Statistical significance was determined with an ANOVA test followed by a Bonferroni's post-hoc test. Results: The number of normal neurons in sham operated rats was 1328±23 (n = 9) and 70% lower in cardiac arrest/vehicle rats (405±78 (n = 5), p<0.001 sham vs. CA). IPC was able to provide tolerance against CA since the number of normal neurons were higher by 88% (760±120, n = 5; P<0.01 IPC vs. CA) as compared with the CA group. The number of normal neurons in 10 and 50 mg/kg resveratrol groups were higher by 73% (702±54, n = 7, p<0.05 10 mg vs. CA) and 11% (449±57, n = 7) as compared to CA group, respectively. No significant protection was observed at higher resveratrol dosages (10 mg/kg, 292±15, n = 6). To determine if IPC and resveratrol preconditioning resulted in increased SIRT1 activity, we measured SIRT1 activity following IPC and resveratrol treatments. IPC and resveratrol preconditioning were able to stimulate SIRT-1 activity by 29 % (n = 4, p< 0.02) and 36 % (n = 4, p< 0.01) as compared to control rats (n = 4), respectively. Conclusion: We conclude that preconditioning can be emulated by pre-treating rats with low dosages of resveratrol. Our data suggests that resveratrol and IPC may exert its neuroprotection via activation of the SIRT1 pathway.
|Original language||English (US)|
|Journal||Journal of Cerebral Blood Flow and Metabolism|
|Issue number||SUPPL. 1|
|State||Published - Nov 13 2007|
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine