Back to Search
Start Over
Preventive effects of dexmedetomidine on the development of cognitive dysfunction following systemic inflammation in aged rats.
- Source :
-
Journal of anesthesia [J Anesth] 2017 Feb; Vol. 31 (1), pp. 25-35. Date of Electronic Publication: 2016 Oct 13. - Publication Year :
- 2017
-
Abstract
- Purpose: In the present study, we examined whether and by what mechanisms dexmedetomidine (DMED) prevents the development of systemic inflammation (SI)-induced cognitive dysfunction in aged rats.<br />Methods: Animals received a single intraperitoneal (i.p.) injection of either 5.0 mg/kg lipopolysaccharide (LPS) or vehicle. LPS-treated rats were further divided into three groups: early DMED, late DMED, or midazolam (MDZ) treatment (n = 12 each). Seven days after LPS injection, cognitive function was evaluated using a novel object recognition task, followed by measurement of hippocampal levels of proinflammatory cytokines and Toll-like receptor 4 (TLR-4) expression. For ex vivo experiments, microglia were isolated from the hippocampus for assessment of cytokine response to LPS.<br />Results: LPS-treated rats showed memory deficits, hippocampal neuroinflammation, and TLR-4 upregulation as compared to saline-treated animals. However, early DMED treatment was able to attenuate these SI-induced neurocognitive changes, whereas no benefits were observed in the MDZ and late DMED treatment groups. In ex vivo experiments, early DMED treatment prevented the development of SI-induced excessive microglial hyperactivation, which was blocked by the nonspecific α <subscript>2</subscript> -adrenergic receptor (AR) antagonist atipamezole or the specific α <subscript>2A</subscript> -AR antagonist BRL-44408, but not by the specific α <subscript>2B/C</subscript> -AR antagonist ARC-239. On the other hand, neither DMED nor MDZ had a direct effect on LPS-induced release of pro-inflammatory cytokines from hippocampal microglia at clinically relevant concentrations.<br />Conclusion: Our findings highlight that treatment with DMED during, but not after, peripheral SI can prevent subsequent hippocampal neuroinflammation, overexpression of TLR-4 in microglia, and cognitive dysfunction, as mediated by the α <subscript>2A</subscript> -AR signaling pathway.
- Subjects :
- Aging
Animals
Cognitive Dysfunction chemically induced
Cognitive Dysfunction etiology
Hippocampus physiopathology
Imidazoles pharmacology
Inflammation complications
Isoindoles pharmacology
Isoquinolines pharmacology
Lipopolysaccharides
Male
Memory Disorders
Piperazines pharmacology
Rats
Signal Transduction
Cognitive Dysfunction prevention & control
Dexmedetomidine therapeutic use
Hypnotics and Sedatives therapeutic use
Neuroprotective Agents therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1438-8359
- Volume :
- 31
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of anesthesia
- Publication Type :
- Academic Journal
- Accession number :
- 27738803
- Full Text :
- https://doi.org/10.1007/s00540-016-2264-4