Apoptosis and Delayed Neuronal Damage after Carbon Monoxide Poisoning in the Rat

doi:10.1006/exnr.1997.6584

Experimental Neurology

Volume 147, Issue 1, September 1997, Pages 103-114

https://doi.org/10.1006/exnr.1997.6584 Get rights and content

Abstract

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.

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¹: Current address: Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232.

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Regular ArticleApoptosis and Delayed Neuronal Damage after Carbon Monoxide Poisoning in the Rat

Abstract

Brain Res.

Eur. J. Pharmacol.

Neurosci. Lett.

Neuron.

Free Radical Biol. Med.

Life Sci.

Neuroscience

Free Radical Biol. Med.

Cell

Cognitive Brain Res.

Brain Res.

Free Radical Biol. Med.

Toxicol. Appl. Pharmacol.

Toxicol. Appl. Pharmacol.

Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illness

Ann. Neurol.

Aging, energy, and oxidative stress in neurodegenerative diseases

Ann. Neurol.

Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis

J. Neurochem.

Recovery of energy metabolism in rat brain after carbon monoxide hypoxia

J. Clin. Invest.

Delayed neurologic sequelae in carbon monoxide intoxication

Arch. Neurol.

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Arch. Neurol.

Identification of programmed cell deathin situ

J. Cell Biol.

Carbon monoxide intoxication: Clinical features, neuropathology and mechanisms of injury

J. Toxicol. Clin. Toxicol.

Uber einen Fall von Leuchtgasvergiftung mit doppelseitiger Pallidumerweichung und schwerer Degeneration des tieferen Grosshirnmarklagers

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Regular Article
Apoptosis and Delayed Neuronal Damage after Carbon Monoxide Poisoning in the Rat