Mineralocorticoid receptor mRNA expression is increased in human hippocampus following brief cerebral ischaemia.
BACKGROUND
We have previously reported that neuronal endangerment in vitro and hypothermic transient global ischaemia in vivo each result in increased mineralocorticoid receptor (MR) expression. In both models MR induction is associated with increased neuronal survival, and blocking MR signalling reduces neuronal survival. Furthermore, transgenic overexpression of human MR promotes neuronal survival both in vitro and in vivo.


OBJECTIVE
Here we have assessed whether brief periods of cerebral ischaemia in human subjects, such as occurs in cardiac arrest from which successful resuscitation is achieved, are associated with a sustained increase in hippocampal MR mRNA expression.


METHODS
Human post-mortem brain sections from patients who had died in the weeks following cardiac arrest were analysed for MR mRNA expression by in situ hybridization.


RESULTS
Sustained upregulation of MR mRNA expression was observed in the dentate gyrus region of human hippocampus following a brief episode of cerebral ischaemia.


CONCLUSIONS
This confirms that MR mRNA expression is regulated following neuronal injury in human brain, and suggests that the benefits of increased MR expression seen in animal models of ischaemia may also be observed in humans.
Lai
M
M
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK. m.lai@ed.ac.uk
Bae
S-E
SE
Bell
J E
JE
Seckl
J R
JR
Macleod
M R
MR
D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000378:metabolism*; D005260:Female; D006323:Heart Arrest / Q000401:mortality / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D010784:Photomicrography; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D051028:bcl-2-Associated X Protein