Agmatine: An Emerging Approach for Neuroprotection in Recurrent Ischemic Stroke Events in a Murine Model

Abstract

This study investigates the effect of agmatine on reducing mortality, neurobehavioral alterations, infarct size, and expression of pro‐inflammatory cytokines in mice subjected to bilateral carotid thrombosis. Under pentobarbital anesthesia, the left common carotid artery was exposed to 6% FeCl3. Thirty‐two days later, the same procedure was performed on the right common carotid artery. Subsequently, Agmatine (100 mg/kg) was administered 15 min after the second procedure, and in another experimental group, the dose of Agmatine was repeated at 72 h. Administration of agmatine extended survival in ischemic animals up to 72 h for the single‐dose group and up to 96 h for the repeated‐dose group, without significant increases in neurological deficits or infarct area size. This neurobehavioral effect was also observed in sham animals treated with agmatine. In ischemic animals, agmatine administration improved digging behavior and reduced recovery times, consistently shorter in those animals treated with repeated doses. RT‐PCR analyses revealed a positive regulation of the cytokine IL‐1β in agmatine‐treated animals, which has been associated with recovery stages. The results suggest that the observed effect may be attributed to the multiple interactions of agmatine with ischemic cascade events, highlighting its anti‐inflammatory role.