title: Neuronal damage after repeated 5 minutes of ischemia in the gerbil is preceded by prolonged impairment of protein metabolism.
abstract: The effect of single or repeated episodes of cerebral ischemia on protein biosynthesis and neuronal injury was studied in halothane-anesthetized gerbils by autoradiography of [14C]leucine incorporation into brain proteins and light microscopy. For quantification of the protein synthesis rate, the steady-state precursor pool distribution space for labeled and unlabeled free leucine was determined by clamping the specific activity of [14C]leucine in plasma, and by measuring free tissue leucine in samples taken from various parts of the brain. Control values of protein synthesis were 14.6 +/- 2.2, 5.8 +/- 2.3, 14.2 +/- 3.1, and 10.0 +/- 3.8 nmol g-1 min-1 (means +/- SD) in the frontal cortex, striatum, CA1 sector, and thalamus, respectively. Following a single episode of 5 or 15 min of ischemia, protein synthesis recovered to normal in all brain regions except the CA1 sector, where it returned to only 50% of control after 6 h and to less than 20% after 3 days of recirculation. After three episodes of 5 min of ischemia spaced at 1 h intervals, protein synthesis remained severely suppressed in all brain regions after both 6 h and 3 days of recirculation. Inhibition of protein synthesis after 6 h predicted histological injury after 3 days of recirculation. In animals submitted to a single episode of 5 or 15 min of ischemia, histological damage was restricted to the CA1 sector but injury occurred throughout the brain after three episodes of 5 min of ischemia. These observations demonstrate that persisting inhibition of protein synthesis following cerebral ischemia is an early manifestation of neuronal injury. Prevention of neuronal injury requires restoration of a normal protein synthesis rate.
authors.affiliation: Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Cologne, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Widmann
authors.forename: C
authors.initials: C
authors.lastname: Weber
authors.forename: P
authors.initials: P
authors.lastname: Bonnekoh
authors.forename: M
authors.initials: M
authors.lastname: Schlenker
authors.forename: K A
authors.initials: KA
authors.lastname: Hossmann
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002250:Carbon Radioisotopes; D016923:Cell Death; D004195:Disease Models, Animal; D005260:Female; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D007930:Leucine / Q000378:metabolism; D014176:Protein Biosynthesis; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D007930:Leucine