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Experimental Brain Research

, Volume 88, Issue 1, pp 91–105 | Cite as

Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia: evidence against programmed cell death

  • Jayant Deshpande
  • Kerstin Bergstedt
  • Thomas Lindén
  • Hannu Kalimo
  • Tadeusz Wieloch
Article

Summary

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 subcutanously, 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.

Key words

Cerebral ischemia Glutamate Heat shock protein Hippocampus Programmed cell death Rat Ubiquitin 

Abbreviations

DND

delayed neuronal death

ER

endoplasmic reticulum

GA

Golgi apparatus

HSP

heat shock protein

IR

immunoreactivity

PSD

postsynaptic density

RNA

ribonucleic acid

SER

smooth endoplasmic reticulum

UIR

ubiquitin immunoreactivity

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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Jayant Deshpande
    • 1
    • 2
  • Kerstin Bergstedt
    • 2
  • Thomas Lindén
    • 3
  • Hannu Kalimo
    • 4
  • Tadeusz Wieloch
    • 2
  1. 1.Department of Anesthesiology and Critical Care MedicineThe Johns Hopkins HospitalBaltimoreUSA
  2. 2.Laboratory for Experimental Brain ResearchLund University HospitalSweden
  3. 3.Department of NeuropathologySahlgrenska HospitalGothenburgSweden
  4. 4.Department of AnatomyTurku UniversityTurkuFinland

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