The effect of mitochondrial transplnataion on brain dysfunction in septic rats

Abstract

Sepsis-induced infection is one of the most common cuases of death among patients admitted to the ICU. Despite great endevor, the rate of morbidity and mortaility is still high among these patients. According to the important role of mitochondria in the cellular homeostatsis, this study aimed to analyze the effect of mitochondrial dysfunction on the brain dysfunction in the sesptic rats. Methodes: Male Wistar rats (250–300g) were randomly devided into the 5 following groups (n=6): 1) the control group, 2) Sepsis, 3) Sepsis+Mito1, and 4) Sepsis+Mito2. In order to assess the effect of mitochondrial transplantaion, the septic rats first recived 10 mg/kg of CLP and then recived isolation buffer containing mitochondria (750 μl) in single or two repetitive injections (with a 24-houre interval and the speed of 20 μl). At the end of the experiment, brain function, histopathological alterations in the brain tissue, mitochondrial funtion (membrane potential, ROS, and ATP), the inflammatory cytokines (TNF-α, IL-1β, and IL-6), as well as mitochondrial biogenesis (PGC-1α and Sirt1), fission (Drp1), and fusion (Mrf1 and Mrf2) gene expression levels, and mitochondrial DNA content was assessed. Results: The results showed that sepsis induced brain disfunction and histopathological damges to the brain tissue. Sepsis also deteriorated mitochondrial function, increased the inflammatory cytokines, and reduced the expression levels of mitochondrial biogenesis, fission, and fusion genes. On the other hand, two consecutive injection of mitohodria revered all of these effecst.