CP-0597, a selective bradykinin B2 receptor antagonist, inhibits brain injury in a rat model of reversible middle cerebral artery occlusion.
Stroke
; 28(7): 1430-6, 1997 Jul.
Article
in En
| MEDLINE
| ID: mdl-9227696
ABSTRACT
BACKGROUND AND PURPOSE:
Recent studies demonstrated a significant neuroprotective action of the selective peptide-based bradykinin B2 receptor antagonist CP-0597 after permanent middle cerebral artery (MCA) occlusion (MCAO) in the rat. We therefore evaluated the efficacy of this compound after reversible MCAO in the rat.METHODS:
Male Wistar rats underwent reversible MCAO by insertion of a nylon monofilament to the origin of the MCA. After 1 hour the filament was retracted and the ischemic tissue reperfused. Immediately after MCAO, primed miniosmotic pumps containing either vehicle or CP-0597 (300 ng/kg per minute) were implanted into the subcutaneous space (n = 14 per group). Twenty-four hours after surgery, animals were killed and brains fixed, and 4-micron sections were taken from five sequential tissue blocks labeled A through E and stained with hematoxylin and eosin. Clinical evaluation of rats was performed by neurological scoring and change in body weight.RESULTS:
Treatment with CP-0597 significantly reduced percent increase in hemisphere size of the ischemic hemisphere in all brain sections (C section vehicle, 40.6 +/- 4.3% versus CP-0597, 20.8 +/- 5.3%; P < 0.001), total infarct volume (vehicle, 206.5 +/- 7.7 mm3 versus CP-0597, 94.0 +/- 19.2 mm3; P < .001), cortical infarct volume (vehicle, 145.5 +/- 4.5 mm3 versus CP-0597, 64.0 +/- 15.1 mm3; P < .001), subcortical infarct volume (vehicle, 55.8 +/- 4.1 mm3 versus CP-0597, 27.5 +/- 4.5 mm3; P < .001), and the number of necrotic neurons (vehicle 42.9 +/- 3.8 versus CP-0597, 23.6 +/- 4.7 per field; P < .01). Neurological score (vehicle, 2.78 +/- 0.36 versus CP-0597, 6.29 +/- 0.87 P < .01) and change in body weight (vehicle, -28.7 +/- 2.0 g versus CP-0597, -18.2 +/- 2.8 g; P < .01) were also significantly improved.CONCLUSIONS:
The present data demonstrate the significant overall efficacy profile of CP-0597 in a rat model of reversible MCAO and provide strong rationale for the use of such bradykinin B2 receptor antagonist in the treatment of stroke.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligopeptides
/
Arterial Occlusive Diseases
/
Brain
/
Reperfusion Injury
/
Cerebral Arteries
/
Brain Ischemia
/
Bradykinin Receptor Antagonists
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Stroke
Year:
1997
Document type:
Article
Affiliation country:
United States