Premium
Hypothermia treatment potentiates ERK1/2 activation after traumatic brain injury
Author(s) -
Atkins Coleen M.,
Oliva Anthony A.,
Alonso Ofelia F.,
Chen Shaoyi,
Bramlett Helen M.,
Hu BingRen,
Dietrich W. Dalton
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05720.x
Subject(s) - hypothermia , traumatic brain injury , hippocampal formation , kinase , phosphorylation , hippocampus , ribosomal protein s6 , protein kinase a , ribosomal s6 kinase , neuroprotection , neuroscience , medicine , endocrinology , anesthesia , microbiology and biotechnology , biology , protein phosphorylation , p70 s6 kinase 1 , protein kinase b , psychiatry
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.