NEUROINFLAMMATION IN DIABETIC ENCEPHALOPATHY: MECHANISTIC INSIGHTS, BIOMARKERS, AND EMERGING THERAPEUTIC TARGETS

Diabetic encephalopathy is an increasingly recognized neurological complication of diabetes mellitus, characterized by progressive cognitive decline, structural brain alterations, and impaired neuronal function. Although observed in both type 1 and type 2 diabetes, its underlying mechanisms remain incompletely understood. Chronic hyperglycemia and insulin resistance disrupt cerebral metabolic homeostasis, promoting oxidative stress, mitochondrial dysfunction, and neurovascular impairment. Emerging evidence suggests that neuroinflammation represents a central pathogenic mechanism linking metabolic disturbances to neuronal injury. Persistent activation of glial cells, disruption of blood-brain barrier integrity, and infiltration of peripheral immune cells contribute to sustained production of pro-inflammatory mediators, resulting in synaptic dysfunction, impaired neurogenesis, and neuronal loss in vulnerable brain regions, particularly the hippocampus. In addition, inflammatory signaling pathways, including NF-κB, NLRP3 inflammasome, and MAPK signaling, together with oxidative stress–mediated damage, have been implicated in disease progression in experimental and clinical studies. This review provides a comprehensive overview of the current understanding of neuroinflammatory mechanisms involved in diabetic encephalopathy, critically evaluates emerging biomarkers, and discusses potential therapeutic strategies for early diagnosis and targeted intervention.