Role of adiponectin in mouse brain after seizure (pp. 1-10)
Authors: (Gu Seob Roh)
Abstract: Neuronal cell death after excitotoxicity is correlated with blood-brain barrier (BBB) leakage. After seizures, BBB breakdown and inflammation are observed in the hippocampus. This change in BBB integrity is caused by increased local cerebral pressure that occurs during seizures and inflammatory responses such as cytokine production. Seizures are accompanied by increases in angiogenic factors that correlate to the degree of propagation of epileptic activity in animal models. Thus, a better understanding of the angiogenic mechanisms of seizure is critically important.
In general, adiponectin secreted from adipose tissue regulates energy homeostasis and glucose and lipid metabolism in peripheral organs and enhances insulin sensitivity. Adiponectin has potential anti-diabetic, anti-inflammatory, and anti-atherosclerotic properties. Adiponectin is an abundant circulating plasma protein secreted by adipose tissue and exhibits beneficial effects in the vasculature. Circulating adiponectin levels are decreased in patients with obesity, diabetes, and coronary heart disease. Low adiponectin levels are associated with endothelial dysfunction. However, the effects of adiponectin in the brain are still poorly understood.
A recent study showed that adiponectin secreted into the circulation can interact with the BBB and exerts potent central nervous system effects. The influence of adiponectin on BBB function has been demonstrated by measuring its activity on adiponectin receptors. Expression of adiponectin receptor mRNA has been demonstrated in brain endothelial cells. Adiponectin suppresses pro-inflammatory interleukin-6 release from brain endothelial cells, indicating a modulatory effect of adiponectin on BBB integrity. Recent studies have reported that angiogenesis is associated with BBB permeability in epilepsy. The long-lasting increased permeability of the BBB found to be present in
various limbic regions, which correlated with seizure activity, suggests a role in increased excitability in the epileptogenic foci that can lead to progression of epilepsy.
This chapter presents the current understanding of the actions of adiponectin in the brain, with particular emphasis on BBB integrity following kainic acid-induced seizure.