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Dexmedetomidine confers neuroprotection against transient global cerebral ischemia/reperfusion injury in rats by inhibiting inflammation through inactivation of the TLR-4/NF-κB pathway
- Source :
- Neuroscience Letters. 649:20-27
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Dexmedetomidine (DXM) has anti-inflammatory effects, which is considered an important mechanism of DXM-induced neuroprotection from cerebral ischemia/reperfusion injury. We determined whether the anti-inflammatory effects of DXM are associated with inhibition of the toll-like receptor (TLR)-4/nuclear factor kappa B (NF-κB) pathway in a rat model of transient global cerebral ischemia/reperfusion injury. Fifty rats were randomly assigned to one of five groups (10 rats/group): Group S received no treatment; Group C underwent transient global ischemia (10min); Group D received DXM 30min before ischemia; Group R received resatorvid, a selective TLR-4 antagonist, 30min before ischemia; and Group RD received resatorvid and DXM 30min before ischemia. The numbers of necrotic and apoptotic cells and the levels of TLR-4, NF-κB, and caspase-3 were assessed 1day after ischemia, and pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) were measured before ischemia and 2, 6, and 24h thereafter. The necrotic and apoptotic cell counts and levels of TLR-4, NF-κB, and caspase-3 were higher in Group C than in other groups. TNF-α were higher in Group C than in other groups 2h after ischemia, whereas IL-6 were higher in Group C 6h after ischemia. IL-1β was higher in Group C than in Group D 6 and 24h after ischemia. Our findings suggest that the anti-inflammatory action of DXM via inactivation of the TLR-4/NF-κB pathway, in part, may explain DXM-induced neuroprotection after cerebral ischemia.
- Subjects :
- Male
0301 basic medicine
Ischemia
Apoptosis
Inflammation
Pharmacology
Hippocampus
Neuroprotection
Brain Ischemia
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Interleukin 6
biology
business.industry
General Neuroscience
NF-kappa B
Antagonist
medicine.disease
Toll-Like Receptor 4
Neuroprotective Agents
030104 developmental biology
Reperfusion Injury
Anesthesia
biology.protein
Encephalitis
Tumor necrosis factor alpha
Inflammation Mediators
medicine.symptom
business
Reperfusion injury
Dexmedetomidine
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 03043940
- Volume :
- 649
- Database :
- OpenAIRE
- Journal :
- Neuroscience Letters
- Accession number :
- edsair.doi.dedup.....26cf96e78615483f311a0b6e7c4da95e