title: Whole body hypothermia broadens the therapeutic window of intranasally administered IGF-1 in a neonatal rat model of cerebral hypoxia-ischemia.
abstract: To investigate whether whole body hypothermia after neonatal cerebral hypoxia-ischemia (HI) could broaden the therapeutic window of intranasal treatment of IGF-1 (iN-IGF-1), postnatal day 7 rat pups were subjected to right common carotid artery ligation, followed by 8% oxygen inhalation for 2h. After HI, one group of pups were returned to their dams and kept at room temperature (24.5±0.2°C). A second group of pups were subjected to whole body hypothermia in a cool environment (21.5±0.3°C) for 2 or 4h before being returned to their dams. Two doses of 50 μg recombinant human IGF-1 were administered intranasally at a 1h interval starting at 0, 2 or 4h after hypothermia. Hypothermia decreased the rectal temperature of pups by 4.5°C as compared to those kept at room temperature. While hypothermia or iN-IGF-1 administered 2h after HI alone did not provide neuroprotection, the combined treatment of hypothermia with iN-IGF-1 significantly protected the neonatal rat brain from HI injury. Hypothermia treatment extended the therapeutic window of IGF-1 to 6h after HI. The extended IGF-1 therapeutic window by hypothermia was associated with decreases in infiltration of polymorphonuclear leukocytes and activation of microglia/macrophages and with attenuation of NF-κB activation in the ipsilateral hemisphere following HI.
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Shuying
authors.initials: S
authors.lastname: Lin
authors.forename: Philip G
authors.initials: PG
authors.lastname: Rhodes
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D007334:Insulin-Like Growth Factor I