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.
Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Coleen M
CM
Atkins
Anthony A
AA
Oliva
Ofelia F
OF
Alonso
Shaoyi
S
Chen
Helen M
HM
Bramlett
Bing-Ren
BR
Hu
W Dalton
WD
Dietrich
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