title: Neuroprotective effect of dexmedetomidine on hyperoxia-induced toxicity in the neonatal rat brain.
abstract: Dexmedetomidine is a highly selective agonist of α2-receptors with sedative, anxiolytic, analgesic, and anesthetic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on neurodegeneration, oxidative stress markers, and inflammation following the induction of hyperoxia in neonatal rats. Six-day-old Wistar rats received different concentrations of dexmedetomidine (1, 5, or 10 µg/kg bodyweight) and were exposed to 80% oxygen for 24 h. Sex-matched littermates kept in room air and injected with normal saline or dexmedetomidine served as controls. Dexmedetomidine pretreatment significantly reduced hyperoxia-induced neurodegeneration in different brain regions of the neonatal rat. In addition, dexmedetomidine restored the reduced/oxidized glutathione ratio and attenuated the levels of malondialdehyde, a marker of lipid peroxidation, after exposure to high oxygen concentration. Moreover, administration of dexmedetomidine induced downregulation of IL-1β on mRNA and protein level in the developing rat brain. Dexmedetomidine provides protections against toxic oxygen induced neonatal brain injury which is likely associated with oxidative stress signaling and inflammatory cytokines. Our results suggest that dexmedetomidine may have a therapeutic potential since oxygen administration to neonates is sometimes inevitable.
authors: Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors: Marco
authors: M
authors: Sifringer
authors: Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors: Clarissa
authors: C
authors: von Haefen
authors: Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors: Maria
authors: M
authors: Krain
authors: Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors: Nadine
authors: N
authors: Paeschke
authors: Department of Pediatrics I, Neonatology, University Hospital Essen, 45122 Essen, Germany.
authors: Ivo
authors: I
authors: Bendix
authors: Department of Neonatology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors: Christoph
authors: C
authors: Bührer
authors: Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors: Claudia D
authors: CD
authors: Spies
authors: Department of Neonatology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors: Stefanie
authors: S
authors: Endesfelder
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020927:Dexmedetomidine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D018496:Hyperoxia; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D020927:Dexmedetomidine; D005978:Glutathione
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