title: The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels.
abstract: Dexmedetomidine (DEX) may act as an antioxidant through regulation of TRPM2 and TRPV1 channel activations in the neurons by reducing cerebral ischemia-induced oxidative stress and apoptosis. The neuroprotective roles of DEX were tested on cerebral ischemia (ISC) in the cultures of rat primary hippocampal and DRG neurons. Fifty-six rats were divided into five groups. A placebo was given to control, sham control, and ISC groups, respectively. In the third group, ISC was induced. The DEX and ISC+DEX groups received intraperitoneal DEX (40 μg/kg) 3, 24, and 48 hours after ISC induction. DEX effectively reversed capsaicin and cumene hydroperoxide/ADP-ribose-induced TRPV1 and TRPM2 densities and cytosolic calcium ion accumulation in the neurons, respectively. In addition, DEX completely reduced ISC-induced oxidative toxicity and apoptosis through intracellular reactive oxygen species production and depolarization of mitochondrial membrane. The DEX and ISC+DEX treatments also decreased the expression levels of caspase 3, caspase 9, and poly (ADP-ribose) polymerase in the hippocampus and DRG. In conclusion, the current results are the first to demonstrate the molecular level effects of DEX on TRPM2 and TRPV1 activation. Therefore, DEX can have remarkable neuroprotective impairment effects in the hippocampus and DRG of ISC-induced rats.
authors.affiliation: Unit of Anesthesiology and Reanimation, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Süleyman Demirel, Isparta, Turkey.
authors.forename: Hatice
authors.initials: H
authors.lastname: Akpınar
authors.affiliation: Department of Neuroscience, Institute of Health Science, University of Süleyman Demirel, Isparta, Turkey.|Center of Neuroscience, University of Süleyman Demirel, Isparta, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Nazıroğlu
authors.affiliation: Department of Neuroscience, Institute of Health Science, University of Süleyman Demirel, Isparta, Turkey.
authors.forename: İshak Suat
authors.initials: İS
authors.lastname: Övey
authors.affiliation: Department of Neuroscience, Institute of Health Science, University of Süleyman Demirel, Isparta, Turkey.
authors.forename: Bilal
authors.initials: B
authors.lastname: Çiğ
authors.affiliation: Unit of Microbiology, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Süleyman Demirel, Isparta, Turkey.
authors.forename: Orhan
authors.initials: O
authors.lastname: Akpınar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001927:Brain Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D020927:Dexmedetomidine / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050053:TRPM Cation Channels / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D050053:TRPM Cation Channels; D050916:TRPV Cation Channels; C557080:Trpm2 protein, rat; C493922:Trpv1 protein, rat; D020927:Dexmedetomidine; D002118:Calcium