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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

Photograph of brains in sham-operated animal (A), and ischemic rats received vehicle (B) or 0.1 mg/kg candesartan (C). Animals received Evans blue 30 minutes after surgery or middle cerebral artery occlusion (MCAO). The presence of blue color depicted in B and C indicates that extravasation of Evans blue has occurred during ischemia/reperfusion injuries in the right side of the brain and its intensity is related to the quantity of damages of the cerebral vasculature of the lesioned side
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Figure 4: Photograph of brains in sham-operated animal (A), and ischemic rats received vehicle (B) or 0.1 mg/kg candesartan (C). Animals received Evans blue 30 minutes after surgery or middle cerebral artery occlusion (MCAO). The presence of blue color depicted in B and C indicates that extravasation of Evans blue has occurred during ischemia/reperfusion injuries in the right side of the brain and its intensity is related to the quantity of damages of the cerebral vasculature of the lesioned side

Mentions: Blood-brain barrierintegrity disruption. Figure 4 is a sample photograph of the brain of the rats exposed to Evans blue extravasation technique. Evans blue extravasation colors the brain tissue blue in the lesioned hemispheres of ischemic rats. The absence of blue color in the right and the left hemispheres of sham (Fig. 4A) indicated that the induction of anesthesia, neck surgery, or manipulation of the carotid arteries per se did not affect BBB integrity. The appearances of bluish color in the lesioned hemispheres of ischemic rats indicated that the 60-min occlusion of the right MCA induced different magnitudes of BBB disruption (Fig. 4B and C). Qualitative comparisons of the blue color areas of ischemic hemispheres indicated that candesartan at dose of 0.1 mg/kg was able to attenuate BBB disruption (Fig. 4C). Figure 5 shows Evans blue concentrations of right side and left side of the brains of sham and ischemic rats receiving the vehicle or candesartan (0.1 mg/kg). There was no statistically significant difference between the Evans blue concentrations of left side brains of such groups. Moreover, there was no statistically significant difference between the Evans blue concentrations of left and right side of the brains of sham-operated rats. Evans blue concentration of ischemic hemisphere in control rats was significantly more than that in sham-operated rats. Pre-treatment with candesartan (0.1 mg/kg) significantly lowered Evans blue concentration and reduced BBB integrity disruption by 54.9% (mean ± SEM, 5.63 ± 0.7 µg/g vs. 12.5 ± 1.94 µg/g, P<0.01).


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)

Photograph of brains in sham-operated animal (A), and ischemic rats received vehicle (B) or 0.1 mg/kg candesartan (C). Animals received Evans blue 30 minutes after surgery or middle cerebral artery occlusion (MCAO). The presence of blue color depicted in B and C indicates that extravasation of Evans blue has occurred during ischemia/reperfusion injuries in the right side of the brain and its intensity is related to the quantity of damages of the cerebral vasculature of the lesioned side
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Photograph of brains in sham-operated animal (A), and ischemic rats received vehicle (B) or 0.1 mg/kg candesartan (C). Animals received Evans blue 30 minutes after surgery or middle cerebral artery occlusion (MCAO). The presence of blue color depicted in B and C indicates that extravasation of Evans blue has occurred during ischemia/reperfusion injuries in the right side of the brain and its intensity is related to the quantity of damages of the cerebral vasculature of the lesioned side
Mentions: Blood-brain barrierintegrity disruption. Figure 4 is a sample photograph of the brain of the rats exposed to Evans blue extravasation technique. Evans blue extravasation colors the brain tissue blue in the lesioned hemispheres of ischemic rats. The absence of blue color in the right and the left hemispheres of sham (Fig. 4A) indicated that the induction of anesthesia, neck surgery, or manipulation of the carotid arteries per se did not affect BBB integrity. The appearances of bluish color in the lesioned hemispheres of ischemic rats indicated that the 60-min occlusion of the right MCA induced different magnitudes of BBB disruption (Fig. 4B and C). Qualitative comparisons of the blue color areas of ischemic hemispheres indicated that candesartan at dose of 0.1 mg/kg was able to attenuate BBB disruption (Fig. 4C). Figure 5 shows Evans blue concentrations of right side and left side of the brains of sham and ischemic rats receiving the vehicle or candesartan (0.1 mg/kg). There was no statistically significant difference between the Evans blue concentrations of left side brains of such groups. Moreover, there was no statistically significant difference between the Evans blue concentrations of left and right side of the brains of sham-operated rats. Evans blue concentration of ischemic hemisphere in control rats was significantly more than that in sham-operated rats. Pre-treatment with candesartan (0.1 mg/kg) significantly lowered Evans blue concentration and reduced BBB integrity disruption by 54.9% (mean ± SEM, 5.63 ± 0.7 µg/g vs. 12.5 ± 1.94 µg/g, P<0.01).

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