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We have demonstrated previously that pretreatment with an angiotensin II type 2 receptor (AT₂R) agonist is neuroprotective against a subsequent stroke independent of any changes in blood pressure. Therefore, in the current study, we have examined the potential neuroprotective effect of AT₂R stimulation initiated after stroke induction to mimic the clinical setting. Intracerebroventricular administration of the AT₂R agonist CGP42112 was commenced 6 hours after an ischemic stroke had been induced in conscious spontaneously hypertensive rats. CGP42112 given over 4 doses in the same rats (3 µg/kg per dose centrally) at 6, 24, 48, and 72 hours after stroke induction reduced total infarct volume (32±13 mm³ versus vehicle, 170±49 mm³; P<0.05) and improved motor function. Furthermore, we have demonstrated that AT₂R stimulation after stroke increased neuronal survival, decreased apoptosis, and caused an …