Glucocorticoid activation of two types of adrenocorticosteroid receptors (ACRs), the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR), influences the vulnerability of hippocampal neurons to insult. To examine the potential impact of ACR activation following traumatic brain injury (TBI), the current study assesses regulation of MR and GR expression and glucocorticoid levels following controlled cortical impact (CCI). Male Sprague-Dawley rats were pretreated for 48 h with vehicle, the MR antagonist spironolactone, or the GR antagonist mifepristone (RU486). On day three, subjects were sham-operated or injured by unilateral CCI. In situ hybridization analysis determined that pretreatment with either MR antagonist spironolactone or GR antagonist RU486 increased 24-h hippocampal GR mRNA levels in sham-operated animals only, suggesting that MR and GR regulation of GR mRNA is suppressed following TBI. Injury decreased GR mRNA levels in the ipsilateral dentate gyrus of all pretreatment groups and bilaterally increased MR mRNA levels in CA3 of antagonist-pretreated animals. One day post-injury, plasma corticosterone levels were comparable in sham and injured animals pretreated with vehicle. A separate group of animals that did not receive pretreatment injections prior to sham operation or injury were included for a 24-h time course analysis of plasma ACTH and corticosterone levels. Injury increased hypothalamic-pituitary-adrenal (HPA) activation for approximately 6 h following injury. These results indicate that hippocampal ACR mRNA levels and HPA activation are altered by TBI. Regulation of MR and GR expression following TBI may influence hippocampal neuron viability by modulating glucocorticoid signaling after injury.
|Number of pages||9|
|State||Published - Aug 23 2002|
Bibliographical noteFunding Information:
This work was supported by AG12962 (J.P.H.), AG10836 (J.P.H.), AG00242 (D.L.M.), NS39828 (S.W.S.), and KSCHIRT (S.W.S.). The authors would like to thank Mark Dolgas and Katie Kraft for expert technical assistance.
- Cortical impact
ASJC Scopus subject areas
- Neuroscience (all)
- Molecular Biology
- Clinical Neurology
- Developmental Biology