Apoptosis and delayed neuronal damage after carbon monoxide poisoning in the rat

Claude A. Piantadosi, Jing Zhang, Edward D. Levin, Rodney J. Folz, Donald E. Schmechel

Research output: Contribution to journalArticlepeer-review

212 Scopus citations


Delayed neurological damage after CO hypoxia was studied in rats to determine whether programmed cell death (PCD), in addition to necrosis, is involved in neuronal death. In rats exposed to either air or CO (2500 ppm), microdialysis in brain cortex and hippocampus was performed to determine the extent of glutamate release and hydroxyl radical generation during the exposures. Groups of control and CO-exposed rats also were tested in a radial maze to assess the effects of the CO exposure on learning and memory. At 3, 7, and 21 days after CO exposure brains were perfusion-fixed and hematoxylin- eosin (H&E) was used to assess injury and to select regions for further examination. DNA fragmentation was sought by examining cryosections with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) reaction. We found significant increases in glutamate release and ·OH generation during and immediately after CO hypoxia. CO-exposed rats showed learning and memory deficits after exposure associated with heterogeneous cell loss in cortex, globus pallidus, and cerebellum. The frontal cortex was affected most seriously; the damage was slight at Day 3, increased at Day 7, and persistent at Day 21 after CO exposure. TUNEL staining was positive at all three time points, and TUNEL-labeled cells were distributed similarly to eosinophilic cells. The number of cells stained by TUNEL was less than by H&E and amounted to 2 to 5% of all cell nuclei in regions of injury. Ultrastructural features of both neuronal necrosis and apoptosis also were observed readily by electron microscopy. These findings indicate that both necrosis and apoptosis (PCD) contribute to CO poisoning- induced brain cell death.

Original languageEnglish (US)
Pages (from-to)103-114
Number of pages12
JournalExperimental Neurology
Issue number1
StatePublished - Sep 1997

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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