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.

The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels

“…found that DEX treatment decreased lipid peroxidation levels in the brains of rats with ischemia-induced brain injuries. The results of this study were supported by the findings of Sifringer et al 3. and Kose et al 19…”

“…These observations suggest that DEX has an antioxidant role against cerebral ischemia-induced oxidative stress in the HIPPO neurons. Sifringer et al 3. reported that oxidative stress levels in the brains of hyperoxia-exposed developing rats were decreased by DEX treatment.…”

“…An accumulating body of evidence indicates that abnormalities of Ca 2+ homeostasis is caused by excessive levels of free oxygen radicals in rats with cerebral ischemia23. In other words, there is mounting evidence to suggest that cell death after cerebral ischemia and spinal cord injury (SCI) is predominantly mediated by high amount of reactive oxygen species (ROS) and the subsequent over-production of poly (ADP-ribose [ADPR]) polymerase-1 (PARP-1), ultimately leading to mitochondrial dysfunction, release of apoptosis-inducing factors, and cell death456.…”

General Anesthesia With Dexmedetomidine and Remifentanil in a 3-Year-Old Child: An Alternative Anesthetic Regimen to Allay Parental Concerns of the Potential Neurocognitive Effects of General Anesthesia

“…However, to date, there are limited reports of its use as the primary part of a general anesthetic regimen [12][13][14]. Beneficial and protective effects on the central nervous system during hypoxia or ischemia have been demonstrated with dexmedetomidine in animal studies [15][16][17][18][19]. Unlike agents that act as GABA agonists or NMDA antagonists, animal data have demonstrated limited impact on apoptosis and neurocognitive outcome [20,21].…”

Hyperoxia and the Immature Brain

“…In 6-day-old Wistar rat pups, dexmedetomidine application significantly reduced hyperoxia-induced neurodegeneration and IL-1β mRNA and protein levels after 24 h of hyperoxia. Moreover, pretreatment with dexmedetomidine normalises the reduced/oxidised glutathione ratio as well as reduced levels of lipid peroxidation [187] . Whether this compound is protective in other experimental models of brain injury needs to be further investigated.…”