Dose-related effects of ciproxifan on brain tissue in rats with cerebral ischemia-reperfusion

Abstract

PurposeCerebral ischemia is the result of decreased or interrupted blood flow to the brain. It is the third leading cause of death after cardiovascular disease and cancer. Cerebral ischemia is reversible or irreversible in neurons in the affected area, and subsequent free radical damage can be exacerbated if reperfusion occurs. Ciproxifan is used to study the involvement of histaminergic neurons in different phases such as wakefulness and cognition. We wanted to find out whether ciproxifan has a protective effect on the brain of rats with cerebral ischemia-reperfusion injury.Materials and methodsA total of 64 adult rats (32 male and 32 female) were used for the experiment. Eight cages were formed with randomly selected rats. No substance was administered to the rats in Group 1 and no surgical procedure was performed. The cerebral ischemia-reperfusion model (clamping of the left common carotid artery for 15 min followed by reperfusion for 24 h) was applied to rats in Group 2, Group 3, and Group 4 after 7 days/single dose of saline and ciproxifan (10 mg/kg, 30 mg/kg). After that, the activitymeter, forced swim test (FST), and Morris water maze (MWM) were performed on all animals.ResultsRats treated with ciproxifan exhibit neurons and glial cells with histologic structures similar to those of the control group, and interestingly, these differences became more pronounced with increasing dose. Rats administered ciproxifan improved motor coordination, decreased total distance behavior, and improved learning ability. However, when the groups were compared by sex, no significant difference was found in the parameters.ConclusionThus, we could conclude that ciproxifan has a protective effect on the brain to a certain extent, regardless of the dose. Cerebral ischemia is one of the leading causes of death.Cerebral ischemia is a common mechanism of acute brain injury that results from impaired blood flow to the brain.Ciproxifan is a well-investigated histamine H3 receptor inverse agonist/antagonist.Ciproxifan presynaptically inhibits glutamate release in rat hippocampus