Abstract
Traumatic brain injury (TBI) results in significant hippocampal pathology and hippocampal-dependent memory loss, both of which are alleviated by hypothermia treatment. To elucidate the molecular mechanisms regulated by hypothermia after TBI, rats underwent moderate parasagittal fluid-percussion brain injury. Brain temperature was maintained at normothermic or hypothermic temperatures for 30 min prior and up to 4 h after TBI. The ipsilateral hippocampus was assayed with Western blotting. We found that hypothermia potentiated extracellular signal-regulated kinase 1/2 (ERK1/2) activation and its downstream effectors, p90 ribosomal S6 kinase (p90RSK) and the transcription factor cAMP response element-binding protein. Phosphorylation of another p90RSK substrate, Bad, also increased with hypothermia after TBI. ERK1/2 regulates mRNA translation through phosphorylation of mitogen-activated protein kinase-interacting kinase 1 (Mnk1) and the translation factor eukaryotic initiation factor 4E (eIF4E). Hypothermia also potentiated the phosphorylation of both Mnk1 and eIF4E. Augmentation of ERK1/2 activation and its downstream signalling components may be one molecular mechanism that hypothermia treatment elicits to improve functional outcome after TBI.
| Original language | English |
|---|---|
| Pages (from-to) | 810-819 |
| Number of pages | 10 |
| Journal | European Journal of Neuroscience |
| Volume | 26 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 1 2007 |
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Keywords
- CREB
- ERK1/2
- Fluid-percussion
- Hypothermia
- Traumatic brain injury
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Hypothermia treatment potentiates ERK1/2 activation after traumatic brain injury. / Atkins, Coleen M; Oliva, Anthony A.; Alonso, Ofelia F.; Chen, Shaoyi; Bramlett, Helen; Hu, Bing Ren; Dalton Dietrich, W.
In: European Journal of Neuroscience, Vol. 26, No. 4, 01.08.2007, p. 810-819.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hypothermia treatment potentiates ERK1/2 activation after traumatic brain injury
AU - Atkins, Coleen M
AU - Oliva, Anthony A.
AU - Alonso, Ofelia F.
AU - Chen, Shaoyi
AU - Bramlett, Helen
AU - Hu, Bing Ren
AU - Dalton Dietrich, W.
PY - 2007/8/1
Y1 - 2007/8/1
N2 - Traumatic brain injury (TBI) results in significant hippocampal pathology and hippocampal-dependent memory loss, both of which are alleviated by hypothermia treatment. To elucidate the molecular mechanisms regulated by hypothermia after TBI, rats underwent moderate parasagittal fluid-percussion brain injury. Brain temperature was maintained at normothermic or hypothermic temperatures for 30 min prior and up to 4 h after TBI. The ipsilateral hippocampus was assayed with Western blotting. We found that hypothermia potentiated extracellular signal-regulated kinase 1/2 (ERK1/2) activation and its downstream effectors, p90 ribosomal S6 kinase (p90RSK) and the transcription factor cAMP response element-binding protein. Phosphorylation of another p90RSK substrate, Bad, also increased with hypothermia after TBI. ERK1/2 regulates mRNA translation through phosphorylation of mitogen-activated protein kinase-interacting kinase 1 (Mnk1) and the translation factor eukaryotic initiation factor 4E (eIF4E). Hypothermia also potentiated the phosphorylation of both Mnk1 and eIF4E. Augmentation of ERK1/2 activation and its downstream signalling components may be one molecular mechanism that hypothermia treatment elicits to improve functional outcome after TBI.
AB - Traumatic brain injury (TBI) results in significant hippocampal pathology and hippocampal-dependent memory loss, both of which are alleviated by hypothermia treatment. To elucidate the molecular mechanisms regulated by hypothermia after TBI, rats underwent moderate parasagittal fluid-percussion brain injury. Brain temperature was maintained at normothermic or hypothermic temperatures for 30 min prior and up to 4 h after TBI. The ipsilateral hippocampus was assayed with Western blotting. We found that hypothermia potentiated extracellular signal-regulated kinase 1/2 (ERK1/2) activation and its downstream effectors, p90 ribosomal S6 kinase (p90RSK) and the transcription factor cAMP response element-binding protein. Phosphorylation of another p90RSK substrate, Bad, also increased with hypothermia after TBI. ERK1/2 regulates mRNA translation through phosphorylation of mitogen-activated protein kinase-interacting kinase 1 (Mnk1) and the translation factor eukaryotic initiation factor 4E (eIF4E). Hypothermia also potentiated the phosphorylation of both Mnk1 and eIF4E. Augmentation of ERK1/2 activation and its downstream signalling components may be one molecular mechanism that hypothermia treatment elicits to improve functional outcome after TBI.
KW - CREB
KW - ERK1/2
KW - Fluid-percussion
KW - Hypothermia
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=34547978336&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547978336&partnerID=8YFLogxK
U2 - 10.1111/j.1460-9568.2007.05720.x
DO - 10.1111/j.1460-9568.2007.05720.x
M3 - Article
C2 - 17666079
AN - SCOPUS:34547978336
VL - 26
SP - 810
EP - 819
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
SN - 0953-816X
IS - 4
ER -