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This book explores the emerging therapeutic potential of purinergic signaling modulation across different stages of cerebrovascular injury. It presents a comprehensive overview of how P2X4 receptor activation or inhibition affects microglial polarization, neuroinflammation, neuronal survival, and post-stroke behavioral outcomes. Integrating molecular neuroscience, pharmacology, and translational medicine, the text delineates the dual temporal roles of P2X4 receptors-early neuroprotection in acute ischemia and regulation of neuroplasticity to mitigate chronic post-stroke depression. The book highlights recent experimental models, receptor-selective ligands, and clinical perspectives for designing time-sensitive interventions that bridge acute neuroprotection with long-term mental health recovery in stroke patients.