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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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Brain water content in left side and right side of brains in sham-operated rats, vehicle-treated control, and 0.1 mg/kg candesartan-treated ischemic rats (n = 8). †P<0.001 compared with sham group; *P<0.001 compared with control group
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Figure 3: Brain water content in left side and right side of brains in sham-operated rats, vehicle-treated control, and 0.1 mg/kg candesartan-treated ischemic rats (n = 8). †P<0.001 compared with sham group; *P<0.001 compared with control group

Mentions: Edema formation. The values of ABWC of the left and the right hemispheres of sham and left hemispheres of the ischemic rats were not statistically different (Fig. 3). Ischemia elevated brain water content of the lesioned hemispheres (right) of control ischemia rats to 83.3 ± 0.35%, while pre-ischemic blockade of AT1 receptors with candesartan (0.1 mg/kg) could significantly diminish BWC (mean ± SEM, 80.3 ± 0.28%, P<0.001, Fig. 3). The brain edema in ischemia control rats was significantly more than that in sham-operated rats. Pre-treatment with candesartan (0.1 mg/kg) significantly reduced the brain edema formation provoked by I/R injury by 59.2% (mean ± SEM, 1.64 ± 0.38% vs. 4.02 ± 0.32% P<0.001).


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)

Brain water content in left side and right side of brains in sham-operated rats, vehicle-treated control, and 0.1 mg/kg candesartan-treated ischemic rats (n = 8). †P<0.001 compared with sham group; *P<0.001 compared with control group
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Brain water content in left side and right side of brains in sham-operated rats, vehicle-treated control, and 0.1 mg/kg candesartan-treated ischemic rats (n = 8). †P<0.001 compared with sham group; *P<0.001 compared with control group
Mentions: Edema formation. The values of ABWC of the left and the right hemispheres of sham and left hemispheres of the ischemic rats were not statistically different (Fig. 3). Ischemia elevated brain water content of the lesioned hemispheres (right) of control ischemia rats to 83.3 ± 0.35%, while pre-ischemic blockade of AT1 receptors with candesartan (0.1 mg/kg) could significantly diminish BWC (mean ± SEM, 80.3 ± 0.28%, P<0.001, Fig. 3). The brain edema in ischemia control rats was significantly more than that in sham-operated rats. Pre-treatment with candesartan (0.1 mg/kg) significantly reduced the brain edema formation provoked by I/R injury by 59.2% (mean ± SEM, 1.64 ± 0.38% vs. 4.02 ± 0.32% P<0.001).

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