Abstract

 Systemic inflammatory disorders such as malaria, diabetes, and arthritis have long been recognized for their multi
organ effects, yet their impact on the central nervous system (CNS) remains an expanding area of research. Chronic 
inflammation and oxidative stress constitute the main pathological link between these systemic diseases and 
neurodegeneration. In malaria, inflammatory cytokine surges and oxidative injury disrupt the blood–brain barrier 
and trigger neuronal apoptosis. Diabetes-induced neurotoxicity arises from hyperglycemia-mediated oxidative 
stress, mitochondrial dysfunction, and microvascular impairment. Similarly, in arthritis, persistent systemic 
inflammation and oxidative stress alter neuronal metabolism and promote neuroinflammation. This review explores 
the molecular and cellular mechanisms underlying neurotoxicity in systemic inflammatory disorders, emphasizing 
the roles of reactive oxygen species (ROS), cytokine signaling, and microglial activation. It also discusses potential 
therapeutic interventions targeting redox and inflammatory pathways, including antioxidant therapy, cytokine 
modulation, and neuroprotective phytochemicals. Understanding the interplay between systemic inflammation and 
neural injury offers valuable insights into developing strategies for mitigating CNS complications in metabolic and 
infectious diseases.