title: AMP-dependent hypothermia affords protection from ischemic brain injury.
abstract: In light of the relevance of therapeutic hypothermia to stroke treatment, we investigated whether 5'-adenosine monophosphate (AMP)-dependent cooling affords protection from ischemic brain injury. We show that hypothermia by AMP is because of adenosine A1 receptor (A1R) activation and is not invariantly associated with hypotension. Inhibition of ecto-5'-nucleotidase-dependent constitutive degradation of brain extracellular AMP by methylene-ADP (AMPCP) also suffices to prompt A1R-dependent hypothermia without hypotension. Both intraischemic and postischemic hypothermia by AMP or AMPCP reduce infarct volumes and mortality of mice subjected to transient middle cerebral artery occlusion. Data disclose that AMP-dependent hypothermia is of therapeutic relevance to treatment of brain ischemia.
authors.affiliation: Department of Preclinical and Clinical Pharmacology University of Florence, Florence, Italy. mirko.muzzi@unifi.it
authors.forename: Mirko
authors.initials: M
authors.lastname: Muzzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiarugi
mesh_terms: D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007036:Hypothermia, Induced; D008297:Male; D051379:Mice
chemical_list: D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate