P0199 - Eszopiclone prevents apnea-induced programmed cell death (Apoptosis) in the forebrain and brainstem of guinea pigs

Abstract

Background and Aims:

Hypoxia that occurs in conjunction with sleep-related breathing disorders, such as Obstructive Sleep Apnea, as well as processes associated with cerebral ischemia, have deleterious effects on the morphology and functioning of the hippocampus. In previous studies, we determined that a decrease in oxygenation produces neuroexcitotoxicity that eventuates in apoptosis, i.e., programmed cell death, that can be reduced by the activation of GABAergic processes.

Methods:

In the present experiment, which was conducted in adult guinea pigs, in vivo, we examined the effects of the administration of eszopiclone, which is a hypnotic that activates various GABAA subunit receptors, on apoptosis in various CNS sites.

Results:

Recurrent periods of apnea, which were induced for a period of 3-5 hours, produced significant apoptosis in various brain regions. Compared with control data, there was a highly statistically significant decrease in the number of apoptotic cells in the forebrain (hippocampus, amygdala, and prefrontal, cingulate, and insular cortices) and in the brainstem (e.g., dorsal raphe) in animals that were administered eszopiclone prior to the induction of recurrent apnea.

Conclusions:

We conclude that eszopiclone is capable of providing neuroprotection for the degradative, apoptotic consequences of a decrease in oxygenation of cerebral tissue that arises as a consequence of disease and disorders that involve hypoxia or ischemia. We therefore suggest, in addition to its hypnotic effects, that eszopiclone produces neuroprotection for hypoxia-induced neurodegeneration in the forebrain as well as in the brainstem.

Support for this study provided by Sepracor Inc., Marlborough, MA.