Ischemic stroke and post-stroke depression: the role of agomelatine

Abstract

Ischemic stroke (IS) is a leading cause of death globally. IS occurs due to a blockage of cerebral arteries, leading to neuronal injury, tissue death, and brain infarcts. This induces lack of oxygenation to the brain which induces neuroinflammation, characterised by interactions involving molecules which can exacerbate brain damage but also aid recovery through processes like microglial phagocytosis. Post-stroke depression (PSD) affects 30–33% of stroke survivors, complicating recovery with various symptoms. The pathophysiology of PSD involves disruptions in the glutamatergic and monoaminergic systems, the gut-brain axis, and neuroinflammation. Agomelatine, an atypical antidepressant, can potentially treat both IS and PSD. It acts as a melatonin receptor agonist and a serotonin receptor antagonist, enhancing dopamine and norepinephrine availability in the prefrontal cortex. Agomelatine’s neuroprotective, anti-inflammatory, antioxidative, and antiapoptotic properties have been demonstrated in research, where it reduces reactive oxygen species (ROS) levels and activates the Nrf2 pathway, promoting antioxidative enzyme expression. Additionally, it prevents microglial activation by inhibiting the toll-like receptor 4 (TLR4)/nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) pathway, thus reducing inflammation. This review examines the pathophysiology of IS and PSD, highlighting agomelatine’s multifaceted therapeutic potential. Agomelatine’s distinct pharmacological profile and minimal side effects make it a compelling candidate for IS and PSD treatment, necessitating further exploration to optimise stroke management and improve patient outcomes.

Keywords

Ischemic stroke / neuroinflammation / post-stroke depression / agomelatine / neuroprotection / antioxidative therapy

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