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Infarct volume and functional outcome after pre- and postoperative administration of metyrapone, a steroid synthesis inhibitor, in focal brain ischemia in the rat

Risedal, Anette LU ; Nordborg, C and Johansson, Barbro LU (1999) In European Journal of Neurology 6(4). p.481-486
Abstract
High blood levels of glucocorticoids are associated with increased mortality, confusion and poor functional outcome in stroke patients. It has been proposed that inhibition of glucocorticoids in acute stroke might be beneficial, but experimental data are conflicting and no long-term follow-up study has been reported. We have studied whether pre- or postoperative administration of metyrapone, a steroid synthesis inhibitor, can influence long-term outcome after ligation of the right middle cerebral artery (MCA) distal to the striatal branches in hypertensive rats. Metyrapone (200 mg/kg) was administered either 30 min before or 1, 12 and 24 h after MCA occlusion. Limb placements and ability to traverse a rotating pole were evaluated pre- and... (More)
High blood levels of glucocorticoids are associated with increased mortality, confusion and poor functional outcome in stroke patients. It has been proposed that inhibition of glucocorticoids in acute stroke might be beneficial, but experimental data are conflicting and no long-term follow-up study has been reported. We have studied whether pre- or postoperative administration of metyrapone, a steroid synthesis inhibitor, can influence long-term outcome after ligation of the right middle cerebral artery (MCA) distal to the striatal branches in hypertensive rats. Metyrapone (200 mg/kg) was administered either 30 min before or 1, 12 and 24 h after MCA occlusion. Limb placements and ability to traverse a rotating pole were evaluated pre- and postoperatively. Infarct size, histology and GFAP immunoreactivity were evaluated on 5 microm coronal sections from brains perfused in situ 4 weeks after the ischemic event. Pretreatment did not influence outcome, whereas postoperative administration of metyrapone significantly increased infarct volume (P < 0.05). Post-treated rats performed significantly worse than vehicle-treated rats on the rotating pole 3 weeks after the operation (P < 0.05). Our results do not support the hypothesis that inhibition of glucocorticoid synthesis improves outcome after cerebral ischemia. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
rats, focal cerebral ischemia, glucocorticoids, metyrapone, stroke outcome, behavior, infarct volume
in
European Journal of Neurology
volume
6
issue
4
pages
481 - 486
publisher
Wiley-Blackwell
external identifiers
  • pmid:10362903
  • scopus:0032814395
ISSN
1351-5101
DOI
10.1046/j.1468-1331.1999.640481.x
language
English
LU publication?
yes
id
5fc2db39-c8a6-4891-ad80-7b1612b7ce44 (old id 1115189)
date added to LUP
2016-04-01 12:12:04
date last changed
2022-03-28 21:40:25
@article{5fc2db39-c8a6-4891-ad80-7b1612b7ce44,
  abstract     = {{High blood levels of glucocorticoids are associated with increased mortality, confusion and poor functional outcome in stroke patients. It has been proposed that inhibition of glucocorticoids in acute stroke might be beneficial, but experimental data are conflicting and no long-term follow-up study has been reported. We have studied whether pre- or postoperative administration of metyrapone, a steroid synthesis inhibitor, can influence long-term outcome after ligation of the right middle cerebral artery (MCA) distal to the striatal branches in hypertensive rats. Metyrapone (200 mg/kg) was administered either 30 min before or 1, 12 and 24 h after MCA occlusion. Limb placements and ability to traverse a rotating pole were evaluated pre- and postoperatively. Infarct size, histology and GFAP immunoreactivity were evaluated on 5 microm coronal sections from brains perfused in situ 4 weeks after the ischemic event. Pretreatment did not influence outcome, whereas postoperative administration of metyrapone significantly increased infarct volume (P &lt; 0.05). Post-treated rats performed significantly worse than vehicle-treated rats on the rotating pole 3 weeks after the operation (P &lt; 0.05). Our results do not support the hypothesis that inhibition of glucocorticoid synthesis improves outcome after cerebral ischemia.}},
  author       = {{Risedal, Anette and Nordborg, C and Johansson, Barbro}},
  issn         = {{1351-5101}},
  keywords     = {{rats; focal cerebral ischemia; glucocorticoids; metyrapone; stroke outcome; behavior; infarct volume}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{481--486}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{European Journal of Neurology}},
  title        = {{Infarct volume and functional outcome after pre- and postoperative administration of metyrapone, a steroid synthesis inhibitor, in focal brain ischemia in the rat}},
  url          = {{http://dx.doi.org/10.1046/j.1468-1331.1999.640481.x}},
  doi          = {{10.1046/j.1468-1331.1999.640481.x}},
  volume       = {{6}},
  year         = {{1999}},
}