Uncontrolled neuroinflammation following cerebral ischemia-reperfusion is a core pathophysiological process driving secondary brain injury and leading to long-term neurological dysfunction. For decades, traditional “anti-inflammatory” strategies targeting the inhibition of key pro-inflammatory pathways have repeatedly failed in clinical translation, compelling a fundamental re-evaluation of the biological nature of inflammation.
Inflammation is not a process that passively subsides upon stimulus removal but a dynamic one that requires active “resolution” through endogenous programs to restore tissue homeostasis. Within this precisely regulated program, a family of endogenous lipid mediators derived from polyunsaturated fatty acids—Specialized Pro-resolving Mediators (SPMs)—act as central executors.
This review systematically proposes a translational framework for post-stroke inflammation management, shifting from traditional “passive anti-inflammation” to “active pro-resolution.” We first delve into the translational challenges and theoretical limitations of conventional anti-inflammatory therapies. Subsequently, we elaborate on the biosynthetic network of SPMs, their major families (lipoxins, resolvins, protectins, and maresins), and their pleiotropic biological functions, including halting neutrophil infiltration, reprogramming macrophage/microglial functions, enhancing the efficiency of apoptotic cell clearance (efferocytosis), and maintaining blood-brain barrier integrity.
Neuroinflammatory dynamics after cerebral ischemia-reperfusion: a pivot from suppression to orchestration:
Specific clinical trial results, numerical data, and explicit outcome metrics are not provided in the source text.