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

Area of Science:

• Neuroscience
• Pharmacology
• Immunology

Background:

• Ischemic stroke is a leading cause of mortality and disability worldwide.
• Current treatments for ischemic stroke are limited, necessitating the exploration of novel therapeutic agents.
• Agmatine, a biogenic amine, has demonstrated neuroprotective and anti-inflammatory properties in various preclinical models.

Purpose of the Study:

• To evaluate the efficacy of agmatine in mitigating mortality and neurobehavioral deficits following bilateral carotid artery thrombosis in mice.
• To assess the impact of agmatine on infarct size and the expression of pro-inflammatory cytokines in an ischemic stroke model.
• To investigate the potential neuroprotective and anti-inflammatory mechanisms of agmatine in the context of ischemic stroke.

Main Methods:

• A mouse model of bilateral carotid artery thrombosis was induced using ferric chloride (FeCl3).
• Agmatine was administered either as a single dose or repeated doses following the induction of ischemia.
• Mortality, neurobehavioral alterations, infarct size, and cytokine expression (IL-1β) were assessed.

Main Results:

• Agmatine administration significantly extended survival in ischemic mice, with repeated doses showing a more pronounced effect.
• Agmatine treatment did not increase neurological deficits or infarct size, and improved digging behavior and recovery times.
• RT-PCR analysis revealed a positive regulation of the cytokine IL-1β in agmatine-treated animals, suggesting a role in recovery.

Conclusions:

• Agmatine demonstrates significant neuroprotective effects in a mouse model of ischemic stroke, improving survival and functional recovery.
• The observed benefits of agmatine may be attributed to its anti-inflammatory actions and modulation of cytokine expression.
• Agmatine represents a promising therapeutic candidate for ischemic stroke, warranting further investigation.