Hypothermia treatment potentiates ERK1/2 activation after traumatic brain injury.
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.
Atkins
Coleen M
CM
Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Oliva
Anthony A
AA
Alonso
Ofelia F
OF
Chen
Shaoyi
S
Bramlett
Helen M
HM
Hu
Bing-Ren
BR
Dietrich
W Dalton
WD
D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000201:enzymology* / Q000523:psychology / Q000628:therapy*; D051786:Cyclic AMP Response Element Modulator / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D039561:Eukaryotic Initiation Factor-4E / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000502:physiology; D007036:Hypothermia, Induced; D007150:Immunohistochemistry; D007858:Learning / Q000502:physiology; D007859:Learning Disabilities / Q000209:etiology / Q000523:psychology; D008297:Male; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D039561:Eukaryotic Initiation Factor-4E; D012333:RNA, Messenger; D051786:Cyclic AMP Response Element Modulator; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3