title: Programmable microchip monitoring of post-stroke pyrexia: effects of aspirin and paracetamol on temperature and infarct size in the rat.
abstract: BACKGROUND
  Recent studies have demonstrated spontaneous and prolonged hyperthermia following stroke in both humans and rodents. However, a full characterization of these pyretic changes and the effects of anti-pyretic drugs on outcome is not available.
  
  
  METHODS
  The aims of this study were to monitor conscious body temperature (n=10 per group) using programmable microchips for up to 24 h in rats following either permanent (p) or 90 min transient (t) middle cerebral artery occlusion (MCAO) or sham surgery, and to evaluate the relationship to hypothalamic damage. Also, the effects of anti-pyretic drug therapy on body temperature and infarct volume were evaluated in animals treated with vehicle, optimal doses of either aspirin or paracetamol (250 mg/kg i.p.) following pMCAO (n=10 per group).
  
  
  RESULTS
  At 1 h, body temperature significantly (P<0.01) increased to 38.6+/-0.2 degrees C following tMCAO and 38.9+/-0.1 degrees C following pMCAO compared with sham-operated animals (37.1+/-0.1 degrees C). Sustained hyperthermia (> or =38.1 degrees C) was observed for up to 24 h following pMCAO but approached baseline within 30 min (37.6+/-0.2 degrees C) following tMCAO with reperfusion. The post-stroke pyrexia was related to the degree of ischemia where hypothalamic damage was observed in (80%) of the animals undergoing pMCAO and (0%) in the tMCAO group (P<0.05). Treatment with paracetamol (250 mg/kg i.p.) significantly attenuated (P<0.05) but did not normalize core body temperature up to 2 h (38.2+/-0.4 degrees C) compared with vehicle treated animals (39.3+/-0.1 degrees C). Aspirin had no effect on temperature under these conditions. Hypothalamic damage and lesion volume were not different between animals treated with paracetamol (253.3+/-8.5 mm(3)), aspirin (264.0+/-11.6 mm(3)) or vehicle (274.4+/-8.2 mm(3)).
  
  
  CONCLUSIONS
  This study is the first to demonstrate the utility of programmable microchips to monitor serial changes in post-stroke hyperthermia. The sustained post-stroke pyrexia and negative effects of antipyretic treatment may be attributed to the extensive hypothalamic injury suggesting that better pharmacologic approaches to reduce body temperature should be identified and evaluated for brain protection in severe experimental stroke.
authors.affiliation: GlaxoSmithKline, High Throughput Biology, Discovery Research, 709 Swedeland Road, PO Box 1539, King of Prussia, PA 19406, USA. jeffrey_j_legos@gsk.com
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Legos
authors.forename: Arduino A
authors.initials: AA
authors.lastname: Mangoni
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Read
authors.forename: Colin A
authors.initials: CA
authors.lastname: Campbell
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Irving
authors.forename: Jenny
authors.initials: J
authors.lastname: Roberts
authors.forename: Frank C
authors.initials: FC
authors.lastname: Barone
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Parsons
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D005334:Fever / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007031:Hypothalamus / Q000473:pathology / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012984:Software; D013686:Telemetry / Q000295:instrumentation
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D001241:Aspirin