EVALUATION OF THE NEUROPROTECTIVE EFFECT OF AGMATINE IN FEMALE MICE WITH RECURRENT ISCHEMIC STROKE

Cerebral ischemia represents a major global health concern, accounting for approximately 80–85% of cerebrovascular diseases, the second leading cause of death and a major source of disability worldwide, with a particularly severe impact in females due to delayed medical intervention and higher rates of mortality, disability, depression, and dementia. In this context, our research group aims to evaluate agmatine, a biogenic amine, as a potential neuroprotective agent capable of modulating multiple components of the ischemic cascade, including the attenuation of inflammatory responses that exacerbate neuronal injury and contribute to secondary damage.
In this study, female CD1 mice (16 weeks of age) underwent estrogen deprivation by ovariectomy, and thrombus formation was induced by topical application of FeCl₃ to both common carotid arteries, one per event, 32 days apart. The Burrowing Test was used to assess nesting behavior, and the severity of neurobehavioral impairments following ischemic insult was evaluated using a 10-point scale before and after surgery. Animals received intraperitoneal agmatine (100 mg/kg) or vehicle 15 minutes after the second thrombotic event.
In our hands, agmatine treatment led to an overall reduction in neurobehavioral deficits and enhanced burrowing performance. These findings suggest that agmatine confers neuroprotective effects in the context of repeated cerebral ischemic events, and that such effects are modulated by systemic physiological determinants. Our data provide novel insights into sex-specific mechanisms of ischemic injury and recovery, supporting the development of personalized therapeutic strategies targeting the distinct clinical needs of women.