title: Proteomic analysis of hypothalamic injury in heatstroke rats.
abstract: Ischemic and oxidative damage to the hypothalamus may be associated with decreased heat tolerance as well as heatstroke formation. The present study explores the hypothalamic proteome mechanisms associated with heatstroke-mediated hypothalamic ischemia, and oxidative damage. Heatstroke rats had hypotension, hypothalamic ischemia, and lethality. In addition, they had hyperthermia and hypothalamic blood-brain-barrier disruption, oxidative stress, activated inflammation, and neuronal apoptosis and degeneration. 2DE combined LC-MS/MS revealed that heatstroke-induced ischemic injury and apoptosis were associated with upregulation of L-lactate dehydrogenase but downregulation of both dihydropyriminase-related protein and 14-3-3 Zeta isoform protein. Heat-induced blood-brain-barrier disruption might be related to upregulation of glial fibrillary acidic protein. Oxidative stress caused by heatstroke might be related to upregulation of cytosolic dehydrogenase-1. Also, heat-induced overproduction of proinflammatory cytokines might be associated with downregulation of stathmin 1. Heat-induced hypothalamic ischemia, apoptosis, injury (or upregulation of L-lactate dehydrogenase), blood-brain-barrier disruption (or upregulation of glial fibrillary acidic protein), oxidative stress (or upregulation of cytosolic dehydrogenase-1), and activated inflammation (or downregulation of stathmin 1) were all significantly reversed by whole body cooling. Our data indicate that cooling therapy improves outcomes of heatstroke by modulating hypothalamic proteome mechanisms.
authors: Department of Surgery and Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan.
authors: Chien-Ming
authors: CM
authors: Chao
authors: Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.|Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors: Bor-Chih
authors: BC
authors: Cheng
authors: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors: Chia-Ying
authors: CY
authors: Chen
authors: Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
authors: Mao-Tsun
authors: MT
authors: Lin
authors: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.|The Ph.D. Program for Neural Regenerative Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Ching-Ping
authors: CP
authors: Chang
authors: Department of Neurosurgery, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Shun-Tai
authors: ST
authors: Yang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D018883:Heat Stroke / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D062385:Hydroxybenzoates / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism* / Q000503:physiopathology*; D007036:Hypothermia, Induced; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D020543:Proteome / Q000032:analysis*; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D016207:Cytokines; D062385:Hydroxybenzoates; D020543:Proteome; D009569:Nitric Oxide; C009135:2,3-dihydroxybenzoic acid
keywords: Animal proteomics; Body cooling; Heat stroke; Hypothalamus