title: The effect of stepwise cerebral hypoperfusion on energy metabolism and amyloid precursor protein (APP) in cerebral cortex and hippocampus in the adult rat.
abstract: To study the relationship between cerebral blood flow, energy metabolism, and the formation of amyloid precursor protein (APP), an in vivo animal model was established in which stepwise long-term cerebral hypoperfusion states were induced. Adult rats underwent a stepwise chronic cerebral hypoperfusion by crosswise occlusion of the carotid and vertebral arteries with different periods and severity of hypoperfusion until the final steady-state experiment. Investigations of metabolic compounds were done in hippocampus and parietotemporal cerebral cortex. The analysis of energy-rich phosphates and adenosine was examined by HPLC analysis. Substrate concentrations of pyruvate and lactate were measured spectrophotometrically. The APP holoprotein was investigated by immunblot technique. Long-term cerebral hypoperfusion induced a decrease of energy-rich phosphates in the brain areas studied, whereas the concentration of adenosine and the ATP turnover were increased. Pyruvate decreased, and lactate was increased, pointing to a shift in the cytoplasmatic redox state. More severe changes were found in parietotemporal cerebral cortex in comparison to the hippocampus. After 2-vessel occlusion, the concentration of APP decreased, whereas the APP concentration was significantly increased in rat brain after 4-vessel occlusion. It has been demonstrated for the first time in vivo that the reduction in cerebral energy metabolism alters the formation of APP due to cerebral hypoperfusion.
authors.affiliation: Department of Anesthesiology, University of Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Plaschke
authors.forename: T
authors.initials: T
authors.lastname: Ranneberg
authors.forename: J
authors.initials: J
authors.lastname: Bauer
authors.forename: M
authors.initials: M
authors.lastname: Weigand
authors.forename: S
authors.initials: S
authors.lastname: Hoyer
authors.forename: H J
authors.initials: HJ
authors.lastname: Bardenheuer
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004734:Energy Metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016564:Amyloid beta-Protein Precursor