Abstract
To elucidate the mechanism of ischemia-induced signal transduction in vivo, we investigated the effect of the targeted disruption of the α and Δ isoforms of the cAMP-responsive element-binding protein (CREB) on c-fos and heat-shock protein (hsp) 72 gene induction. Permanent focal ischemia was induced by occlusion of the middle cerebral artery of the CREB mutant mice (CREB(-/-), n = 5) and the wild-type mice (n = 6). Three hours after onset of ischemia, the neurologic score was assessed and pictorial measurements of ATP and cerebral protein synthesis (CPS) were carried out to differentiate between the ischemic core (where ATP is depleted), the ischemic penumbra (where ATP is preserved but CPS is inhibited), and the intact tissue (where both ATP and CPS are preserved). There were no significant differences in neurologic score or in ATP, pH, and CPS between the two groups, suggesting that the sensitivity of both strains to ischemia is the same. Targeted disruption of the CREB gene significantly attenuated c-fos gene induction in the periischemic ipsilateral hemisphere but had no effect on either c-fos or hsp72 mRNA expression in the penumbra. The observations demonstrate that CREB expression, despite its differential effect on c-fos, does not modulate acute focal ischemic injury.
| Original language | English |
|---|---|
| Pages (from-to) | 1325-1335 |
| Number of pages | 11 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 18 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 01-01-1998 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Neurology
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
Cite this
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Attenuated c-fos mRNA induction after middle cerebral artery occlusion in CREB knockout mice does not modulate focal ischemic injury. / Hata, Ryuji; Gass, Peter; Mies, Günter; Wiessner, Christoph; Hossmann, Konstantin Alexander.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 18, No. 12, 01.01.1998, p. 1325-1335.Research output: Contribution to journal › Article
TY - JOUR
T1 - Attenuated c-fos mRNA induction after middle cerebral artery occlusion in CREB knockout mice does not modulate focal ischemic injury
AU - Hata, Ryuji
AU - Gass, Peter
AU - Mies, Günter
AU - Wiessner, Christoph
AU - Hossmann, Konstantin Alexander
PY - 1998/1/1
Y1 - 1998/1/1
N2 - To elucidate the mechanism of ischemia-induced signal transduction in vivo, we investigated the effect of the targeted disruption of the α and Δ isoforms of the cAMP-responsive element-binding protein (CREB) on c-fos and heat-shock protein (hsp) 72 gene induction. Permanent focal ischemia was induced by occlusion of the middle cerebral artery of the CREB mutant mice (CREB(-/-), n = 5) and the wild-type mice (n = 6). Three hours after onset of ischemia, the neurologic score was assessed and pictorial measurements of ATP and cerebral protein synthesis (CPS) were carried out to differentiate between the ischemic core (where ATP is depleted), the ischemic penumbra (where ATP is preserved but CPS is inhibited), and the intact tissue (where both ATP and CPS are preserved). There were no significant differences in neurologic score or in ATP, pH, and CPS between the two groups, suggesting that the sensitivity of both strains to ischemia is the same. Targeted disruption of the CREB gene significantly attenuated c-fos gene induction in the periischemic ipsilateral hemisphere but had no effect on either c-fos or hsp72 mRNA expression in the penumbra. The observations demonstrate that CREB expression, despite its differential effect on c-fos, does not modulate acute focal ischemic injury.
AB - To elucidate the mechanism of ischemia-induced signal transduction in vivo, we investigated the effect of the targeted disruption of the α and Δ isoforms of the cAMP-responsive element-binding protein (CREB) on c-fos and heat-shock protein (hsp) 72 gene induction. Permanent focal ischemia was induced by occlusion of the middle cerebral artery of the CREB mutant mice (CREB(-/-), n = 5) and the wild-type mice (n = 6). Three hours after onset of ischemia, the neurologic score was assessed and pictorial measurements of ATP and cerebral protein synthesis (CPS) were carried out to differentiate between the ischemic core (where ATP is depleted), the ischemic penumbra (where ATP is preserved but CPS is inhibited), and the intact tissue (where both ATP and CPS are preserved). There were no significant differences in neurologic score or in ATP, pH, and CPS between the two groups, suggesting that the sensitivity of both strains to ischemia is the same. Targeted disruption of the CREB gene significantly attenuated c-fos gene induction in the periischemic ipsilateral hemisphere but had no effect on either c-fos or hsp72 mRNA expression in the penumbra. The observations demonstrate that CREB expression, despite its differential effect on c-fos, does not modulate acute focal ischemic injury.
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U2 - 10.1097/00004647-199812000-00007
DO - 10.1097/00004647-199812000-00007
M3 - Article
VL - 18
SP - 1325
EP - 1335
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 12
ER -