Abstract P603: Lifetime Increase In Cerebral Angiotensin-(1-7) Induces Neuroprotection In A Model Of Brain Ischemia And Reperfusion

Abstract

Recent studies showed that angiotensin-(1-7) [Ang-(1-7)] has cerebroprotective actions in ischemic and hemorrhagic stroke. Here we tested the hypothesis that transgenic rat (TGR-7371), which overexpress Ang-(1-7) in the brain, would exhibit neuroprotection in a model of brain ischemia/reperfusion by bilateral common carotid arteries occlusion (BCCAo). Evaluation of neurological deficit scores and bilateral asymmetry test (BAT) were performed 7 days after transient (25 min) BCCAo in TGR-7371 and Sprague-Dawley (SD) rats. The integrity of the blood-brain barrier (BBB) was assessed by the degree of extravasation of Evans blue dye (EB) intravenously injected and expressed as μg/100 mg of tissue. Cytokine levels were quantified in the whole brain through Elisa assay and expressed as pg/100 mg of tissue. Neurological deficits, such as ptosis palpebral, walking in circles, and/or ataxia, were observed in both SD-BCCAo and TGR-BCCAo, contrasting to sham-operated groups. However, TGR-BCCAo showed a significant lower neurological score and latency in BAT when compared with SD-BCCAo. SD-BCCAo showed greater extravasation of EB (13.5 ± 2; n=4) than sham group (2.4 ± 0.07; n=4). TGR-BCCAo had a significant reduced amount of EB (8 ± 1.5; n=5), indicating attenuation in loss of integrity of the BBB. As expected, levels of pro-inflammatory cytokines were increased in SD-BCCAo (IL-1β: 225 ± 16, IL-6: 290 ± 24, TNF-α: 404 ± 39) when compared to SD control rats (IL-1β: 24 ± 1, IL-6: 24 ± 3, TNF-α: 50 ± 4). Interestingly, TGR-BCCAo presented lower levels of cytokines (IL-1β: 125 ± 15; IL-6: 205 ± 27; TNF-α: 286 ± 6) when compared to SD-BCCAo. Levels of IL-10 were higher in SD-BCCAo than in SD control (112 ± 5 vs 29 ± 5) and even higher in TGR-BCCAo (172 ± 27). The present study shows that lifetime increase in cerebral expression of Ang-(1-7) induces neuroprotection in experimental global cerebral ischemia and reperfusion.