Investigating the effect of intranasal administration of caffeine on the function of inflammatory pathways in the brain of global ischemia model rats

Abstract

Cerebral ischemia is one of the causes of disability that leads to sensory, motor and cognitive disorders. So far, no effective treatment has been introduced to restore normal function following cerebral ischemia. Caffeine is a nervous system stimulant compound widely used to enhance cognitive functions in human and animal studies. The present study investigated the effect of intranasal administration of caffeine on the memory function and pro-inflammatory cytokines in the brain of a rat model of transient global cerebral ischemia. Methods: In this study, 40 male Wistar rats, weighing 200-250 g, were used. The animals were randomly divided into 5 groups of 8 animals in each group: surgical sham, ischemia model, ischemia + caffeine 0.025, ischemia + caffeine 0.05, and ischemia + caffeine 0.1. In animals of ischemia groups, global ischemia was performed by temporary occlusion of common carotid arteries for 10 minutes. Animals were then treated intranasally with 10 microliters of normal saline or caffeine in doses of 0.025, 0.05 and 0.1 mg for 7 days. Social memory test was done to evaluate social memory. In addition, the levels of inflammatory proteins, including tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in the prefrontal cortex (PFC) region were measured by ELISA method. Results: The results of the behavioral test showed that global ischemia led to the devastation of social memory, and caffeine treatment at a dose of 0.1 mg improved the behavioral results in ischemic animals. Also, caffeine 0.1 mg caused a significant decrease in the expression of inflammatory cytokines TNF-α and IL-1β in the PFC area of stroke animals (p<0.05).