TAK-779, a Nonpeptide CC Chemokine Receptor Antagonist, Protects the Brain Against Focal Cerebral Ischemia in Mice

The effect of a nonpeptide CC chemokine receptor antagonist, TAK-779, on ischemic brain injury resulting from 1-hour middle cerebral artery occlusion followed by 48-hour reperfusion was examined in ddY mice. On intracerebroventricular injection of vehicle or TAK-779, infarct volume in the vehicle-treated group was 44.2 +/- 13.2% of the contralateral hemispheric volume, and TAK-779 (25 and 250 ng/mouse) dose-dependently reduced the infarct volume to 35.0 +/- 12.2% and 31.1 +/- 12.9%, respectively. On intravenous injection, infarct volume in the vehicle-treated group was 32.0 +/- 16.1%, and TAK-779 (5 microg per 20 g body weight) significantly reduced this to 22.0 +/- 10.5%. The results showed for the first time that a nonpeptide chemokine receptor antagonist is protective against ischemic brain injury.