Inflammation versus oxidative stress in pathophysiology of alzheimer's disease in rat model

Abstract

Background: Alzheimer's disease (AD) is a highly debilitating neurodegenerative disorder characterized by cognitive dysfunction. Inflammation and oxidative stress are thought to play major roles in the pathophysiology. Which one has the principle role is unclear. Objectives: The role of brain growth factors, cytokines and oxidative biomarkers in cognitive dysfunction induced by Aluminium chloride (AlCl 3) in rats with application of an anti-inflammatory (Cilostazol) and an antioxidant (N-acetyl cysteine, NAC) were investigated to clarify the predominant pathophysiological mechanism involved. Methods: Alzheimer's model group was given AlCl 3 (100 mg/kg) orally for six weeks. Alzheimer's model + NAC, and Alzheimer's model + Cilostazol groups were given (NAC) and Cilostazol respectively one hour before AlCl 3 for the same duration. Results: Anti-inflammatory or antioxidant interventions significantly improved memory retention, which was evaluated by Morris Water Maze, passive avoidance task, and eight-arm radial maze. This improvement was consistent with histological recovery and was mediated by reduction AlCl 3 concentration in the brain hippocampus and frontal cortex, interference with the cholinergic dysfunction, as well as prevention of oxidative damage. In addition, anti-inflammatory agents can modulate superiorly the inflammatory response via reduction of the levels of inflammatory cytokines and adjustment of the levels of brain-derived neurotrophic factors and transforming growth factor B. Conclusions: These finding support the principal role of inflammation in pathophysiology of AD and suggests the potential therapeutic application of anti-inflammatory agents for this condition.