The Role of Microglia in Cognitive Impairment Following Stroke
Microglia are innate immune cells of the central nervous system, analogous to the macrophages that serve the same role elsewhere in the body. Maladaptive inflammatory behavior on the part of microglia is a feature of many age-related conditions in the brain. Researchers here review what is known of the lasting consequences of this sort of microglial overreaction that occur following a stroke. Finding ways to dampen excessive microglial inflammation would likely prove useful in the treatment and prevention of many age-related conditions.
Post-stroke cognitive impairment (PSCI) is a clinical syndrome characterized by cognitive deficits that manifest following a stroke and persist for up to 6 months post-event. This condition is grave, severely compromising patient quality of life and longevity, while also imposing substantial economic burdens on societies worldwide. Despite significant advancements in identifying risk factors for PSCI, research into its underlying mechanisms and therapeutic interventions remains inadequate.
Recently, the role of microglia in PSCI has garnered increasing attention. Microglia, the brain's primary immune and pro-inflammatory cells, are critical to the central nervous system's (CNS) immune response. Evidence suggests that microglia-mediated neuronal damage and dysfunction play a pivotal role in the pathogenesis and progression of PSCI, involving neuropathological changes post-stroke and several signaling pathways implicated in cognitive deficits, such as TLR4, p25/CDK5, Nuclear factor kappa-B (NF-κB), and CX3CR1.
Moreover, existing studies underscore neuroinflammation as a pivotal mechanism in PSCI, with microglia playing a crucial role within this context. This review reveals that microglial activation can be triggered through multiple pathways, leading to the polarization of activated microglia into two distinct phenotypes: M1 and M2. These phenotypes exert divergent effects on PSCI, with M2 microglia serving a protective function, whereas M1 microglia contribute to detrimental outcomes. Identifying strategies to guide the polarization of microglia towards the M2 phenotype during PSCI progression represents a critical avenue for therapeutic intervention.