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Candesartan attenuates ischemic brain edema and protects the blood-brain barrier integrity from ischemia/reperfusion injury in rats.

Panahpour H, Nekooeian AA, Dehghani GA - Iran. Biomed. J. (2014)

Bottom Line: Rats were exposed to 60-min middle cerebral artery (MCA) occlusion.Candesartan at a dose of 0.1 mg/kg, without changing arterial blood pressure, improved neurological dysfunction scoring together with significant reductions in BBB disruption (54.9%), edema (59.2%), and cerebral infarction (54.9%).Inactivation of central AT1 receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Physiology and Pharmacology, Medical School, Ardabil University of Medical Sciences, Ardabil, Iran. h.panahpour@arums.ac.ir.

ABSTRACT

Background: Angiotensin II (Ang II) has an important role on cerebral microcirculation; however, its direct roles in terms of ischemic brain edema need to be clarified. This study evaluated the role of central Ang II by using candesartan, as an AT1 receptor blocker, in the brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia/reperfusion (I/R) injuries in rat.

Methods: Rats were exposed to 60-min middle cerebral artery (MCA) occlusion. Vehicle and non-hypotensive doses of candesartan (0.1 mg/kg) were administered one hour before ischemia. Neurological dysfunction scoring was evaluated following 24 h of reperfusion. Animals were then decapitated under deep anesthesia for the assessments of cerebral infarct size, edema formation, and BBB permeability.

Results: The outcomes of 24 h reperfusion after 60-min MCA occlusion were severe neurological disability, massive BBB disruption (Evans blue extravasation = 12.5 ± 1.94 µg/g tissue), 4.02% edema, and cerebral infarction (317 ± 21 mm3). Candesartan at a dose of 0.1 mg/kg, without changing arterial blood pressure, improved neurological dysfunction scoring together with significant reductions in BBB disruption (54.9%), edema (59.2%), and cerebral infarction (54.9%).

Conclusions: Inactivation of central AT1 receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke.

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Related in: MedlinePlus

Cerebral infarct volume in vehicle-treated control and 0.1 mg/kg candesartan-treated ischemic rats (n = 8). *P<0.001, compared with control group
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Figure 2: Cerebral infarct volume in vehicle-treated control and 0.1 mg/kg candesartan-treated ischemic rats (n = 8). *P<0.001, compared with control group

Mentions: Cerebral infarction. There were no traces of infarction in the left and right hemispheres of sham-operated rats. MCA occlusion of the right hemispheres produced cerebral lesions in control ischemia rats. However, the pre-ischemic blockade of AT1 receptor with a non-hypotensive dose of candesartan (0.1 mg/kg) significantly diminished cerebral lesion volumes by 54.9% (mean ± SEM, 143 ± 14 vs. 317 ± 21 mm3, P<0.001, Fig. 2).


Candesartan attenuates ischemic brain edema and protects the blood-brain barrier integrity from ischemia/reperfusion injury in rats.

Panahpour H, Nekooeian AA, Dehghani GA - Iran. Biomed. J. (2014)

Cerebral infarct volume in vehicle-treated control and 0.1 mg/kg candesartan-treated ischemic rats (n = 8). *P<0.001, compared with control group
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225063&req=5

Figure 2: Cerebral infarct volume in vehicle-treated control and 0.1 mg/kg candesartan-treated ischemic rats (n = 8). *P<0.001, compared with control group
Mentions: Cerebral infarction. There were no traces of infarction in the left and right hemispheres of sham-operated rats. MCA occlusion of the right hemispheres produced cerebral lesions in control ischemia rats. However, the pre-ischemic blockade of AT1 receptor with a non-hypotensive dose of candesartan (0.1 mg/kg) significantly diminished cerebral lesion volumes by 54.9% (mean ± SEM, 143 ± 14 vs. 317 ± 21 mm3, P<0.001, Fig. 2).

Bottom Line: Rats were exposed to 60-min middle cerebral artery (MCA) occlusion.Candesartan at a dose of 0.1 mg/kg, without changing arterial blood pressure, improved neurological dysfunction scoring together with significant reductions in BBB disruption (54.9%), edema (59.2%), and cerebral infarction (54.9%).Inactivation of central AT1 receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Physiology and Pharmacology, Medical School, Ardabil University of Medical Sciences, Ardabil, Iran. h.panahpour@arums.ac.ir.

ABSTRACT

Background: Angiotensin II (Ang II) has an important role on cerebral microcirculation; however, its direct roles in terms of ischemic brain edema need to be clarified. This study evaluated the role of central Ang II by using candesartan, as an AT1 receptor blocker, in the brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia/reperfusion (I/R) injuries in rat.

Methods: Rats were exposed to 60-min middle cerebral artery (MCA) occlusion. Vehicle and non-hypotensive doses of candesartan (0.1 mg/kg) were administered one hour before ischemia. Neurological dysfunction scoring was evaluated following 24 h of reperfusion. Animals were then decapitated under deep anesthesia for the assessments of cerebral infarct size, edema formation, and BBB permeability.

Results: The outcomes of 24 h reperfusion after 60-min MCA occlusion were severe neurological disability, massive BBB disruption (Evans blue extravasation = 12.5 ± 1.94 µg/g tissue), 4.02% edema, and cerebral infarction (317 ± 21 mm3). Candesartan at a dose of 0.1 mg/kg, without changing arterial blood pressure, improved neurological dysfunction scoring together with significant reductions in BBB disruption (54.9%), edema (59.2%), and cerebral infarction (54.9%).

Conclusions: Inactivation of central AT1 receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke.

Show MeSH
Related in: MedlinePlus