Increased oxidation of RNA despite reduced mitochondrial respiration after chronic electroconvulsive stimulation of rat brain tissue.

Major depressive disorder (MDD) affects 350 million people worldwide and is a serious socio-economic burden. The most efficient treatment of MDD is electroconvulsive therapy (ECT), which has been shown to influence the oxidative status believed to be part of the pathophysiology of MDD. We investigated the effects of chronic electroconvulsive stimulation (ECS) on mitochondrial respiration and mitochondrial hydrogen peroxide production, RNA oxidation, and the content of mitochondria in the piriform cortex of the rat. We found reductions of mitochondrial respiration in respiratory states 2 and 3 by 33% and 32%, respectively, and a 23% reduction in electron transfer capacity. RNA oxidation, as measured by 8-oxo-7,8-dihydroguanosine, was increased by 58%, while mitochondrial production of H2O2 was unaffected. The increased oxidative stress may thus be ascribed to extra-mitochondrial sources.

Cerebral Blood Flow and Metabolism in Hepatic Encephalopathy-A Meta-Analysis.

Hepatic Encephalopathy (HE) is associated with abnormalities in brain metabolism of glucose, oxygen and amino acids. In patients with acute liver failure, cortical lactate to pyruvate ratio is increased, which is indicative of a compromised cerebral oxidative metabolism. In this meta-analysis we have reviewed the published data on cerebral blood flow and metabolic rates from clinical studies of patients with HE. We found that hepatic encephalopathy was associated with reduced cerebral metabolic rate of oxygen, glucose, and blood flow. One exemption was in HE type B (shunt/by-pass) were a tendency towards increased cerebral blood flow was seen. We speculate that HE is associated with a disturbed metabolism-cytopathic hypoxia-and that type specific differences of brain metabolism is due to differences in pathogenesis of HE.

Effects of dexamethasone and cox inhibitors on intracranial pressure and cerebral perfusion in the lipopolysaccharide treated rats with hyperammonemia.

INTRODUCTION: Systemic inflammation may affect the brain by aggravating the stage of encephalopathy and increasing intracranial pressure (ICP) especially if liver insufficiency with hyperammonemia is present. The aim of this study was to determine if the influence of concomitant hyperammonemia and lipopolysaccharide (LPS) on the brain can be prevented by dexamethasone and cyclooxygenase (COX) inhibitors. METHOD: Fifty-four male Wistar rats, 6 in each group, were divided into the following groups: Saline+ saline; LPS (2 mg/kg)+saline; LPS+indomethacin (10 mg/kg); LPS+diclofenac (10mg/kg); LPS+dexamethasone (2mg/kg) in experiment A. Experiment-B included the following groups: LPS+NH3 (140 µmol/kg/min)+saline; LPS+NH3+indomethacin; LPS+NH3+diclofenac and LPS+NH3+dexamethasone. ICP was monitored via a catheter placed in cisterna magna and changes in CBF were recorded by laser Doppler flowmetry. RESULTS: LPS with and without NH3 induced a similar increase in plasma 6-keto-prostaglandin-F1α (6-keto-PGF1α) concentration together with a concomitant rise in CBF and ICP. Indomethacin and diclofenac prevented the increase in ICP by LPS alone, and with the addition of NH3 the increase in both CBF and ICP, which was associated with a decrease in 6-keto-PGF1α. Dexamethasone only reduced the LPS induced increase in ICP but not CBF, and partly the 6-keto-PGF1α plasma concentration in the combined setup. CONCLUSION: These data indicate that activation of cycloooxygenases is of central importance for development of cerebral hyperemia and high ICP during concomitant systemic inflammation and hyperammonemia.