title: Analysis of neuronal, glial, endothelial, axonal and apoptotic markers following moderate therapeutic hypothermia and anesthesia in the developing piglet brain.
abstract: Hypothermia (HT) by whole body (WBC) or selective head cooling (SHC) reduces hypoxic-ischemic (HI) brain injury; however, whether prolonged hypothermia and/or anesthesia disrupts immature brain development, eg, increases apoptosis, is unknown. Anesthesia increases apoptosis in immature animals. We investigated whether neuroprotective hypothermia and anesthesia disrupts normal brain development. Thirty-eight pigs <24 h old were randomized between five groups and were killed after 72 h: eighteen received a global hypoxic-ischemic insult under anesthesia, eight subsequently cooled by SHC with WBC to T(rectal) 34.5 degrees C for 24 h, followed by 48 h normothermia (NT) at T(rectal) 39.0 degrees C, while 10 remained normothermic. Sixteen underwent anesthetized sham hypoxic-ischemic, six then following normothermia and 10 following hypothermia protocols. There were four normothermic controls. The hypothermia groups demonstrated significant brain hypothermia. In the hypoxic-ischemic groups this conferred approximately 60% neuroprotection reducing histological injury scores in all brain areas. Immunohistochemical/histochemical analyses of neuronal, glial, endothelial, axonal, transcriptional apoptotic markers in areas devoid of histological lesions revealed no hypothermia/normothermia group and differences whether exposed to hypoxic-ischemic or not. Neither 36-h anesthesia nor 24-h hypothermia produced adverse effects at 4-day survival on a panel of brain maturation/neural death markers in newborn pigs. Longer survival studies are necessary to verify the safety of hypothermia in the developing brain.
authors.affiliation: INSERM, U676, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.forename: John
authors.initials: J
authors.lastname: Dingley
authors.forename: Frank
authors.initials: F
authors.lastname: Plaisant
authors.forename: Helen
authors.initials: H
authors.lastname: Porter
authors.forename: Leslie
authors.initials: L
authors.lastname: Schwendimann
authors.forename: Catherine
authors.initials: C
authors.lastname: Verney
authors.forename: James
authors.initials: J
authors.lastname: Tooley
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001831:Body Temperature / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D019610:Cytoprotection / Q000502:physiology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005452:Fluoresceins; D007036:Hypothermia, Induced / Q000009:adverse effects*; D020925:Hypoxia-Ischemia, Brain / Q000628:therapy*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009930:Organic Chemicals; D034421:Sus scrofa
chemical_list: D018685:Anesthetics, Inhalation; D015415:Biomarkers; D005452:Fluoresceins; D009419:Nerve Tissue Proteins; D009930:Organic Chemicals; C435731:fluoro jade