Sleep deprivation-induced cognitive impairment: Unraveling the role of neuroinflammation

Sleep deprivation (SD) is a common public health issue linked to cognitive decline and neurodegenerative diseases. SD-induced cognitive impairment is closely linked to neuroinflammation, yet the underlying mechanisms remain incompletely understood. This review highlights neuroinflammation as a key mechanism linking SD to cognitive impairment, focusing on microglial activation via the NF-κB pathway, astrocyte dysfunction, oxidative stress, and gut-brain axis disruption. Chronic SD triggers pro-inflammatory cytokine release, neurotransmitter imbalance, and impaired synaptic plasticity, leading to neuronal damage. It also disrupts glymphatic clearance, promoting neurotoxic metabolite buildup. Notably, neuroinflammation and neurotransmitter imbalance reinforce each other in a vicious cycle that accelerates cognitive deterioration. Finally, we outline therapeutic strategies targeting neuroinflammation, including pharmacological agents, natural compounds, and microbiota modulation, that may help preserve cognitive function.