Regulation of ischemic cell death by glucocorticoids and adrenocorticotropic hormone
- PMID: 10051210
- DOI: 10.1016/s0306-4522(98)00213-9
Regulation of ischemic cell death by glucocorticoids and adrenocorticotropic hormone
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.
Similar articles
-
Regulation of ischemic cell death by the lipoic acid-palladium complex, Poly MVA, in gerbils.Exp Neurol. 2004 Sep;189(1):10-5. doi: 10.1016/j.expneurol.2004.05.011. Exp Neurol. 2004. PMID: 15296831
-
Neuroprotective efficacy of nimesulide against hippocampal neuronal damage following transient forebrain ischemia.Eur J Pharmacol. 2002 Oct 25;453(2-3):189-95. doi: 10.1016/s0014-2999(02)02422-6. Eur J Pharmacol. 2002. PMID: 12398903
-
Selegiline treatment after transient global ischemia in gerbils enhances the survival of CA1 pyramidal cells in the hippocampus.Brain Res. 1997 May 23;757(2):260-7. doi: 10.1016/s0006-8993(97)00227-8. Brain Res. 1997. PMID: 9200755
-
The syndrome of acquired glucocorticoid resistance in HIV infection.Baillieres Clin Endocrinol Metab. 1994 Oct;8(4):777-87. doi: 10.1016/s0950-351x(05)80300-3. Baillieres Clin Endocrinol Metab. 1994. PMID: 7811221 Review.
-
Hippocampal glucocorticoid receptors and the regulation of ACTH secretion.Mol Cell Endocrinol. 1990 May 28;71(1):C35-8. doi: 10.1016/0303-7207(90)90067-i. Mol Cell Endocrinol. 1990. PMID: 2163928 Review. No abstract available.
Cited by
-
Vulnerability to stroke: implications of perinatal programming of the hypothalamic-pituitary-adrenal axis.Front Behav Neurosci. 2009 Dec 9;3:54. doi: 10.3389/neuro.08.054.2009. eCollection 2009. Front Behav Neurosci. 2009. PMID: 20057937 Free PMC article.
-
A characterization of cortisol level and adrenal reservation in human cardiopulmonary arrest: systematic review and meta-analysis.Syst Rev. 2021 Oct 8;10(1):266. doi: 10.1186/s13643-021-01820-4. Syst Rev. 2021. PMID: 34625103 Free PMC article.
-
Activation of Trk neurotrophin receptors by glucocorticoids provides a neuroprotective effect.Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4862-7. doi: 10.1073/pnas.0709102105. Epub 2008 Mar 17. Proc Natl Acad Sci U S A. 2008. PMID: 18347336 Free PMC article.
-
Cerebrospinal Fluid Cortisol Mediates Brain-Derived Neurotrophic Factor Relationships to Mortality after Severe TBI: A Prospective Cohort Study.Front Mol Neurosci. 2017 Mar 9;10:44. doi: 10.3389/fnmol.2017.00044. eCollection 2017. Front Mol Neurosci. 2017. PMID: 28337122 Free PMC article.
-
Blocking stroke-induced immunodeficiency increases CNS antigen-specific autoreactivity but does not worsen functional outcome after experimental stroke.J Neurosci. 2015 May 20;35(20):7777-94. doi: 10.1523/JNEUROSCI.1532-14.2015. J Neurosci. 2015. PMID: 25995466 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous