Ketone bodies metabolism during ischemic and reperfusion brain injuries following bilateral occlusion of common carotid arteries in rats

Abstract

Ketone bodies metabolism during ischemic and reperfusion brain injuries following bilateral occlusion of common carotid arteries in ratsKetone bodies metabolism during ischemic and reperfusion brain injuries following bilateral occlusion of common carotid arteries in rats 1 Metabolismo dos corpos cetônicos durante as lesões de isquemia e reperfusão cerebrais após oclusão bilateral das artérias carótidas comuns em ratos ABSTRACT Purpose: To evaluate the in vivo alterations on ketone bodies metabolism after cerebral ischemia/reperfusion through an experimental model of brain ischemia induced by simple occlusion of common carotid arteries (CCAs) in Wistar rats. Methods: Forty-eight male Wistar rats were randomly distributed on two groups (S -Sham; T -Test) and further redistributed into four times sets of study. After bilateral occlusion of CCAs for 30min, the animals of group T were allowed reperfusion for 0, 5, 10 and 15min. Samples of cerebral tissue and systemic arterial blood were collected and the metabolites acetoacetate (ACT) and beta-hydroxybutyrate (BHB) were determined. Results: Cerebral ACT and BHB levels increased significantly in Group T after 30min of carotid occlusion (time 0). The highest brain ketone bodies (ACT+BHB) concentration was verified at 5min of reperfusion, decreasing after 10min of recirculation. Systemic ketone bodies levels increased similarly between test and sham groups. Group S demonstrated a significant increase in cerebral and systemic ACT and BHB concentrations mainly after 40-45min of study. Conclusions: The partial transient acute global brain ischemia induced by the bilateral carotid occlusion in Wistar rats triggered ketogenesis probably due to a central stimulation of catecholamine secretion. There was an increased cerebral uptake of ketone bodies following brain ischemia, reaffirming these metabolites as alternative energy substrates under conditions of cerebral metabolic stress as well as its potential role on neuroprotection. The greatest changes in ketone bodies metabolism were verified at initial minutes of recirculation as a result of the reperfusion injury phenomenon. Key words: Brain ischemia. Reperfusion. Ketone bodies. Metabolism. Rats. RESUMOObjetivo: Avaliar as alterações in vivo no metabolismo dos corpos cetônicos após isquemia/reperfusão cerebral através de um modelo experimental de isquemia cerebral induzido pela simples oclusão das artérias carótidas comuns (CCAs) em ratos Wistar. Métodos: Quarenta e oito ratos Wistar machos foram distribuídos aleatoriamente em dois grupos (SControle; T -Teste) e cada um deles redistribuídos em quatro tempos de estudos. Após oclusão bilateral das CCAs por 30min, permitiu-se reperfusão aos animais do grupo T nos tempos 0, 5, 10 e 15min. Foram coletadas amostras de tecido cerebral e sangue arterial sistêmico e quantificados os metabólitos acetoacetato (ACT) e beta-hidroxibutirato (BHB). Resultados: Os níveis cerebrais de ACT e BHB aumentaram significantemente no Grupo T após 30min de oclusão carotídea (tempo 0). A maior concen...

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