Enteric neuroprotection—A matter of balancing redox potentials, limiting inflammation, and boosting resilience

Abstract The enteric nervous system (ENS) orchestrates intricate and autonomous functions throughout the gastrointestinal (GI) tract. Disruptions in ENS function are associated GI disorders. This mini review focuses on the past decade's research, utilizing rodent models, with an emphasis on protecting enteric neurons from loss. The review specifically looks at efforts to reduce oxidative stress, limit inflammation, and enhance neuronal resilience. Protective interventions including administration of antioxidants and compounds targeting cellular redox buffer systems, are evaluated for their effectiveness in preventing loss of enteric neurons in the ischemia–reperfusion model and streptozotocin‐induced diabetes model. Interventions such as engrafting mesenchymal stem cells and targeting inflammatory signaling pathways in enteric neurons and glial cells are evaluated in inflammatory bowel disease models including the Winnie mouse, DSS‐, and DNBS/TNBS‐induced colitis models. The review also touches upon neuronal resilience, particularly in the context of Parkinson's disease models. Including estrogen's neuroprotective role, and the influence of metal ions on enteric neuronal protection. Understanding the dynamic interplay within the ENS and its role in disease pathogenesis holds promise for developing targeted therapies to effectively manage and treat various GI ailments.