| 2. |
- Deshpande, J, et al.
(author)
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Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia: evidence against programmed cell death.
- 1992
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In: Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. - 0014-4819. ; 88:1, s. 91-105
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Journal article (peer-reviewed)abstract
- The ultrastructural changes in the pyramidal neurons of the CA1 region of the hippocampus were studied 6 h, 24 h, 48 h, and 72 h following a transient 10 min period of cerebral ischemia induced by common carotid occlusion combined with hypotension. The pyramidal neurons showed delayed neuronal death (DND), i.e. at 24 h and 48 h postischemia few structural alterations were noted in the light microscope, while at 72 h extensive neuronal degeneration was apparent. The most prominent early ultrastructural changes were polysome disaggregation, and the appearance of electron-dense fluffy dark material associated with tubular saccules. Mitochondria and nuclear elements appeared intact until frank neuronal degeneration. The dark material accumulated with extended periods of recirculation in soma and in the main trunks of proximal dendrites, often beneath the plasma membrane, less frequently in the distal dendrites and seldom in spines. Protein synthesis inhibitors (anisomycin, cycloheximide) and an RNA synthesis inhibitor (actinomycin D), administered by intrahippocampal injections or subcutaneously, did not mitigate neuronal damage. Therefore, DND is probably not apoptosis or a form of programmed cell death. We propose that the dark material accumulating in the postischemic period represents protein complexes, possibly aggregates of proteins or internalized plasma membrane fragments, which may disrupt vital cellular structure and functions, leading to cell death.
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| 3. |
- Wieloch, Tadeusz, et al.
(author)
-
Protein phosphorylation and the regulation of mRNA translation following cerebral ischemia
- 1993. - C
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In: Neurobiology of Ischemic Brain Damage. - 0079-6123. - 9780444896032 ; 96, s. 179-191
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Book chapter (peer-reviewed)abstract
- This chapter discusses the changes in protein phosphorylation following ischemia, with particular reference to the regulation of the initiation of protein synthesis. Transient cerebral ischemia seems to induce a post-ischemic imbalance between protein kinase and protein phosphatase activities, leading to a net dephosphorylation of proteins in the vulnerable neurons. This imbalance may lead to the persistent changes in processes crucial for neuronal survival such as post-ischemic protein synthesis. The depression of protein synthesis after an ischemic insult most probably is because of a decreased guanine nucleotide exchange factor (GEF) activity, leading to a limited availability of eukaryotic initiation factors (eIF-2) for initiation complex formation. The inhibition of GEF activity in the vulnerable regions could in turn be because of dephosphorylation of GEF, possibly because of tyrosine phosphatase activation and a decreased casein kinase II activity. Post-ischemic inhibition of protein kinase C and calcium calmodulin kinase II may in addition depress eIF-4 activity leading to a selective translation of mRNA such as heat shock mRNA.
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