Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1999 Jan;88(1):319-25.
doi: 10.1016/s0306-4522(98)00213-9.

Regulation of ischemic cell death by glucocorticoids and adrenocorticotropic hormone

Affiliations

Regulation of ischemic cell death by glucocorticoids and adrenocorticotropic hormone

F J Antonawich et al. Neuroscience. 1999 Jan.

Abstract

Transient global ischemia results in delayed selective neuronal death of hippocampal CA1 pyramidal cells. Glucocorticoids increase and adrenalectomy decreases the rate of neuronal death; however, they also produce changes in brain temperature, serum glucose and adrenocorticotropic hormone levels. In order to understand the role of glucocorticoids in regulating ischemic cell death, we studied RU 38486, a glucocorticoid receptor blocker, and Org 2766, a non-steroidogenic adrenocorticotropic hormone 4-9 analog. Male Mongolian gerbils were subjected to 5 min of bilateral carotid artery occlusion under a controlled temperature environment (37.0-38.0 degrees C). Animals were injected with either physiological saline, Org 2766 (10 microg/kg/24 h) or RU 38486 (50 mg/kg/8 h), beginning just prior to the occlusion until killing at either day 4 or 7. Blood was collected for serum glucose and cortisol analysis. Damage was evaluated by blinded counts of CAI neurons. Both RU 38486 and Org 2766 treatment significantly (P<0.004) reduced hippocampal CA1 damage at day 4, but not on day 7. While RU 38486 raised serum cortisol and adrenocorticotropic hormone levels, neither treatment affected temperature or serum glucose. The fact that RU 38486 mimicked adrenalectomy without changing temperature suggests that the decreased rate of cell death resulted from either removal of glucocorticoids or increases in adrenocorticotropic hormone. The ability of Org 2766 to affect this rate strongly suggests that adrenocorticotropic hormone is the active regulatory hormone rather than glucocorticoids. While both RU 38486 and Org 2766 prolong the survival of CA1 neurons after transient global ischemia, only RU 38486, which is available and tested in both animals and humans, can block the detrimental effects of post-ischemia glucocorticoid elevations. Thus, the administration of RU 38486 may be a practical adjunct to other neuroprotective agents for victims of cardiac arrest, anesthetic accidents or drowning.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

LinkOut - more resources