Pancreas-brain axis: exploring the pathogenic mechanisms of pancreatic encephalopathy

Pancreatic encephalopathy (PE) is a severe yet under-recognized neurological complication of acute pancreatitis, characterized by disturbances in consciousness, cognitive impairment, and high mortality. Recent epidemiological evidence indicates that PE occurs more frequently than previously appreciated, particularly in patients with severe disease. The pathogenesis of PE is multifactorial and involves pancreatic enzyme-mediated toxicity, systemic inflammation, metabolic dysregulation, and blood-brain barrier disruption. Emerging studies support the concept of a bidirectional pancreas-brain axis, through which pancreatic injury signals are transmitted to the central nervous system via integrated neural, endocrine, immune, and microbiota-related pathways. This review synthesizes the current evidence on the molecular, cellular, and network-level mechanisms underlying PE, with a focus on neuro-glial-immune interactions, excitotoxicity, mitochondrial dysfunction, and neuroinflammation. We summarize advances in diagnostic biomarkers and discuss the translational potential of emerging therapeutic strategies, including neuromodulation, mitochondrial protection, and short-chain fatty acid supplementation. By providing an integrated framework of the pancreas-brain axis, this review aims to clarify the pathophysiology of PE and highlight future directions for diagnostic and therapeutic development.