Recovery of Monkey Brain after Prolonged Ischemia. II. Protein Synthesis and Morphological Alterations

Abstract

Recovery of protein synthesis following 1 h of complete ischemia of the monkey brain was assessed by 3H-labeled amino acid incorporation in vivo at various postischemic periods between 1.5 and 24 h. The regional autoradiographic patterns obtained were compared on the basis of precursor-product relationships determined biochemically at the end of the tracer incorporation studies. Shortly after ischemia, protein synthesis was severely inhibited, but it gradually recovered with increasing recirculation times. In the cerebellum it returned to almost normal levels within 3 h and in the cortex within 24 h. Hippocampal and thalamic regions, however, did not recover control levels of protein synthesis at 24 h. His-toautoradiographic evaluation of amino acid incorporation in individual neurons revealed recovery of pyramidal neurons in the CA1 and CA3 sectors of the hippocampus within 6 h of recirculation, which, however, was followed by secondary inhibition after longer recirculation. Neurons in cortical layer 5 steadily recovered to near control within 24 h, with the exception of those located in arterial border zones, which returned to only 50% of control at 24 h. Incomplete recovery was also observed in thalamic neurons and Purkinje cells. The regional and histoauto-radiographic pattern of protein synthesis correlated with the morphological appearance of cells. Ischemic cell changes (mainly of the dark type with microvacuolization and perineuronal glial swelling) were marked after short recirculation times but gradually disappeared in parallel with the return of protein synthesis in most regions of the brain. Only in pyramidal cells of the hippocampus, thalamic neurons, and Purkinje cells were changes not reversed during the observation period. The results obtained corroborate the electrophysiological observations reported in the first part of this investigation and support the notion that the majority of the neurons of monkey brain survive complete cerebrocirculatory arrest of 1 h for at least 1 day.

Recovery of Monkey Brain after Prolonged Ischemia. I. Electrophysiology and Brain Electrolytes

“…In the second part of our study, this conclusion will be further substantiateJ by the demonstration of a progressive recovery of protein synthesis and by the structural preservation of the majority of cerebral neurons (Bodsch et al, 1986). These findings are in agreement with similar observations made in our laboratory after 1 h of ischemia in cats (Hossmann and Sato, 1970), but they are in obvious contrast to numerous other in vestigations in which much shorter revival times of the brain have been reported.…”

“…Forty-five minutes before the end of the predetermined recirculation time, a mixture of five tritiated amino acids was injected intravenously for determination of protein biosynthesis, as described in the accompanying article (Bodsch et al, 1986). At the end of this period, the frontal pole of the left hemisphere was removed with a spatula and freeze-clamped in liquid nitrogen.…”

Lubeluzole Pretreatment Does Not Provide Neuroprotection Against Transient Global Cerebral Ischemia in Fetal Sheep Near Term

“…In addition, many other pathophysiological mechanisms such as inhibition of protein synthesis, generation of epileptogenic impulses, etc. are differently regulated in focal and global ischemia and may therefore alter the neuroprotective efficiency of lubeluzole (37)(38)(39)(40)(41). However, there is one study in adult rats indicating that lubeluzole protects the brain from neuronal cell loss after global ischemia (10).…”

Effect of L-carnitine on postischemic inhibition of protein synthesis in the rat brain

“…Postischemic changes including massive remodulation of gene expression (Kogure and Kato 1993;Honkaniemi et al 1996;Yakubov et al 2004) cannot be effective if nearly complete inhibition of protein synthesis persists in the selectively vulnerable regions (Bodsch et al 1986;Thilmann et al 1986). L-carnitine, by its ability to protect translational machinery permits the newly synthesized mRNAs to be translated into functional proteins, thus allowing the altered gene expression to be effective.…”