Neuroprotective effects of dexmedetomidine against hyperoxia-induced injury in the developing rat brain.
Dexmedetomidine (DEX) is a highly selective agonist of α2-receptors with sedative, anxiolytic, and analgesic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on hippocampal neurogenesis, specifically the proliferation capacity and maturation of neurons and neuronal plasticity following the induction of hyperoxia in neonatal rats. Six-day old sex-matched Wistar rats were exposed to 80% oxygen or room air for 24 h and treated with 1, 5 or 10 μg/kg of dexmedetomidine or normal saline. A single pretreatment with DEX attenuated the hyperoxia-induced injury in terms of neurogenesis and plasticity. In detail, both the proliferation capacity (PCNA+ cells) as well as the expression of neuronal markers (Nestin+, PSA-NCAM+, NeuN+ cells) and transcription factors (SOX2, Tbr1/2, Prox1) were significantly reduced under hyperoxia compared to control. Furthermore, regulators of neuronal plasticity (Nrp1, Nrg1, Syp, and Sema3a/f) were also drastically decreased. A single administration of dexmedetomidine prior to oxygen exposure resulted in a significant up-regulation of expression-profiles compared to hyperoxia. Our results suggest that dexmedetomidine may have neuroprotective effects in an acute hyperoxic model of the neonatal rat.
Department of Neonatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Stefanie
S
Endesfelder
Department of Neonatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Hanan
H
Makki
Department of Anesthesiology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Clarissa
C
von Haefen
Department of Anesthesiology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Claudia D
CD
Spies
Department of Neonatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Christoph
C
Bührer
Department of Anesthesiology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Marco
M
Sifringer
D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia; D020927:Dexmedetomidine / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D055495:Neurogenesis / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic / Q000187:drug effects
D018696:Neuroprotective Agents; D020927:Dexmedetomidine; D010100:Oxygen