Int Neurourol J.  2017 Apr;21(Suppl 1):S39-S47. 10.5213/inj.1734884.442.

Dexmedetomidine Oral Mucosa Patch for Sedation Suppresses Apoptosis in Hippocampus of Normal Rats

Affiliations
  • 1Department of Surgery, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon, Korea.
  • 2Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
  • 3College of Pharmacy, Kyung Hee University, Seoul, Korea.
  • 4Department of Anesthesiology and Pain Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea.
  • 5Department of Oral and Maxillofacial Surgery, Kyung Hee University Dental Hospital at Gangdong, College of Dentistry, Kyung Hee University, Seoul, Korea. verycutebear@hanmail.net

Abstract

PURPOSE
Dexmedetomidine, an α2-adrenergic agonist, provides sedative and analgesic effects without significant respiratory depression. Dexmedetomidine has been suggested to have an antiapoptotic effect in response to various brain insults. We developed an oral mucosa patch using dexmedetomidine for sedation. The effects of the dexmedetomidine oral mucosa patch on cell proliferation and apoptosis in the hippocampus were evaluated.
METHODS
A hydrogel oral mucosa patch was adhered onto the oral cavity of physiologically normal rats, and was attached for 2 hours, 6 hours, 12 hours, or 24 hours. Plasma dexmedetomidine concentrations were determined by liquid chromatography- electrospray ionization-tandem mass spectrometry-multiple-ion reaction monitoring (LC-ESI-MS/MS-MRM). Cell proliferation in the hippocampus was detected by Ki-67 immunohistochemistry. Caspase-3 immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and Western blotting for Bax and Bcl-2 were performed to detect hippocampal apoptosis. The levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) in the hippocampus were also measured by Western blotting.
RESULTS
Plasma dexmedetomidine concentration increased according to the attachment time of the dexmedetomidine oral mucosa patch. Hippocampal cell proliferation did not change due to the dexmedetomidine oral mucosa patch, and the dexmedetomidine oral mucosa patch exerted no significant effect on BDNF or TrkB expression. In contrast, the dexmedetomidine oral mucosa patch exerted an antiapoptotic effect depending on the attachment time of the dexmedetomidine oral mucosa patch.
CONCLUSIONS
A dexmedetomidine oral mucosa patch can be used as a convenient tool for sedation, and is of therapeutic value due to its antiapoptotic effects under normal conditions.

Keyword

Dexmedetomidine; Apoptosis; Cell proliferation; Hippocampus; Rats

MeSH Terms

Animals
Apoptosis*
Blotting, Western
Brain
Brain-Derived Neurotrophic Factor
Caspase 3
Cell Proliferation
Dexmedetomidine*
Hippocampus*
Hydrogel
Immunohistochemistry
Mouth
Mouth Mucosa*
Plasma
Protein-Tyrosine Kinases
Rats*
Respiratory Insufficiency
Brain-Derived Neurotrophic Factor
Caspase 3
Dexmedetomidine
Hydrogel
Protein-Tyrosine Kinases
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