Key result
Transgenic rats overproducing Angiotensin-(1-7) demonstrated significantly lower latency in the bilateral asymmetry test and reduced neurological deficit scores compared to wild-type rats after cerebral ischemia.
Why the study?
Recent studies showed that angiotensin-(1-7) has cerebroprotective actions in stroke, motivating testing whether tissue overexpression provides neuroprotection in ischemia and reperfusion.
Does transgenic tissue overexpression of Angiotensin-(1-7) improve neurological outcomes and reduce tissue damage in a rat model of cerebral ischemia/reperfusion?
Does transgenic tissue overexpression of Angiotensin-(1-7) improve neurological outcomes and reduce tissue damage in a rat model of cerebral ischemia/reperfusion?
Answers are grounded in this paper and cite their sources.
Brain overexpression of Angiotensin-(1-7) protects against global cerebral ischemia and reperfusion injury, highlighting the potential of the ACE2/Ang-(1-7) pathway as a therapeutic target in stroke.
Recent studies showed that angiotensin-(1-7) has cerebroprotective actions in stroke. In the present study, we aim to test whether tissue overexpression of Angiotensin-(1-7), mainly in the brain provides neuroprotection in a model of ischemia/reperfusion by bilateral common carotid arteries occlusion/reperfusion (BCCAo/R). Evaluation of neurological deficit scores and bilateral asymmetry test (BAT) were performed seven days after transient BCCAo/R in transgenic rats (TG-7371) overexpressing Angiotensin-(1-7) and Sprague-Dawley (SD) rats. To assess blood-brain barrier (BBB) permeability Evans blue dye (EB) was intravenously injected. Cytokine levels were quantified in the whole brain through Elisa assay and oxidative stress was measured 7 days after ischemia. The expression of AT1 and Mas receptors and inducible nitric oxide synthase (iNOS) was evaluated by RT-PCR. Neurological deficits were observed in both SD-BCCAo/R and TG-BCCAo/R, contrasting to sham-operated groups. However, TG-BCCAo/R showed a significant lower neurological score and latency in BAT when compared with SD-BCCAo/R. BBB integrity in TG-BCCAo/R was improved, since these animals showed lower extravasation of EB than SD-BCCAo/R. Interestingly, TG-BCCAo/R presented lower levels of pro-inflammatory cytokines when compared to SD-BCCAo/R. Levels of IL-10 were higher in SD-BCCAo/R than in SD control and even higher in TG-BCCAo/R. TG-BCCAo/R animals presented decreased levels of TBARS and increase in SOD activity and GSH levels when compared to SD sham rats. RT-PCR results showed higher levels of AT1 receptor and iNOS in SD-BCCAo/R compared to TG-BCCAo/R, but no difference was observed for Mas receptor. The present study shows that lifetime increase in cerebral expression of an Ang-(1-7)-producing fusion protein induces neuroprotection in experimental global cerebral ischemia and reperfusion, reassuring that, pharmacological strategies leading to increase in Ang-(1-7) can be an additional tool for stroke therapy.
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Kangussu et al. (2022) studied Global cerebral ischemia and reperfusion. Transgenic overexpression of Angiotensin-(1-7) vs. Wild-type Sprague-Dawley rats was evaluated on Latency to adhesive removal in the bilateral asymmetry test at 7 days (p=<0.0001). Transgenic rats overproducing Angiotensin-(1-7) demonstrated significantly lower latency in the bilateral asymmetry test and reduced neurological deficit scores compared to wild-type rats after cerebral ischemia.
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