Neuroinflammation is a complex immune response triggered by brain injury or pathological stimuli, and is highly exacerbated in neurodegenerative diseases. It plays a dual role in the central nervous system, promoting repair in acute stages while aggravating disease progression by contributing to neuronal loss, synaptic dysfunction, and glial dysregulation in chronic phases. Inflammatory responses are mainly orchestrated by microglia and infiltrated monocytes, which, when dysregulated, not only harm existing neurons, but also impair the survival and differentiation of neural stem and progenitor cells in the affected brain regions. Modulating neuroinflammation is crucial for harnessing its protective functions while minimizing its detrimental effects. Current therapeutic strategies focus on fine-tuning inflammatory responses through pharmacological agents, bioactive molecules, and stem cell-based therapies. These approaches aim to restore immune homeostasis, support neuroprotection, and promote regeneration in various neurological disorders. However, animal models sometimes fail to reproduce human-specific inflammatory responses in the brain. In this context, stem-cell-derived models provide a powerful tool to study neuroinflammatory mechanisms in a patient-specific and physiologically relevant context. These models facilitate high-throughput screening, personalized medicine, and the development of targeted therapies while addressing the limitations of traditional animal models, paving the way for more targeted and effective treatments.

Gut microbiota has emerged as a key regulator of immune, metabolic, and neuroinflammatory processes, exerting significant influence on central nervous system (CNS) function via the gut-brain axis. Growing evidence suggests that gut dysbiosis not only precedes and worsens stroke severity but is also induced by stroke itself, establishing a bidirectional and self-reinforcing pathological loop. Microbiota-derived metabolites, including short-chain fatty acids and tryptophan derivatives, modulate the activation states of microglial and border-associated macrophage (BAMs), thereby shaping neuroinflammatory responses and tissue repair mechanisms. Although microglia have been extensively studied in this context, the role of BAMs-particularly perivascular-macrophages remains comparatively underexplored, despite their critical involvement in maintaining blood-brain barrier (BBB) integrity and immune surveillance. In addition, dietary patterns strongly influence microbiota composition and, consequently, immune responses within the CNS. Collectively, these findings position gut microbiota as a dynamic regulator of brain-resident immune cells in stroke and highlight diet- and microbiota-targeted interventions as promising therapeutic strategies.