title: Glutamate excitoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.
abstract: Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.
authors.affiliation: Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Universitario de Santiago, University of Santiago de Compostela, IDIS, Santiago de Compostela, Spain. francampos@linc-stg.eu
authors.forename: Francisco
authors.initials: F
authors.lastname: Campos
authors.forename: María
authors.initials: M
authors.lastname: Pérez-Mato
authors.forename: Jesús
authors.initials: J
authors.lastname: Agulla
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanco
authors.forename: David
authors.initials: D
authors.lastname: Barral
authors.forename: Angeles
authors.initials: A
authors.lastname: Almeida
authors.forename: David
authors.initials: D
authors.lastname: Brea
authors.forename: Christian
authors.initials: C
authors.lastname: Waeber
authors.forename: José
authors.initials: J
authors.lastname: Castillo
authors.forename: Pedro
authors.initials: P
authors.lastname: Ramos-Cabrer
mesh_terms: D000210:Acute-Phase Reaction / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D018698:Glutamic Acid / Q000097:blood / Q000633:toxicity*; D007036:Hypothermia, Induced; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D009498:Neurotoxins / Q000097:blood / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000097:blood / Q000473:pathology / Q000503:physiopathology*
chemical_list: D015850:Interleukin-6; D009498:Neurotoxins; D018698:Glutamic Acid