title: Attenuation of neuroinflammation by dexmedetomidine is associated with activation of a cholinergic anti-inflammatory pathway in a rat tibial fracture model.
abstract: Sustained neuroinflammation contributes to the pathogenesis of postoperative cognitive dysfunction. Dexmedetomidine, a selective α-2 adrenergic receptor agonist, exhibits a protective role in the brain. This study investigated whether dexmedetomidine pretreatment attenuates neuroinflammation induced by tibial fracture in rats, as well as the mechanism by which dexmedetomidine provides its neuroprotection. In our study, we observed that tibial fracture significantly increased the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and the expression of nuclear factor-kappa B (NF-κB) in the hippocampus. Overexpression of microglial (CD11b) and astrocytic (GFAP) responses to injury were observed in the hippocampus. Dexmedetomidine pretreatment significantly suppressed the inflammatory responses, as evidenced by lower TNF-α and IL-1β levels, significantly inhibited NF-κB activity, and alleviated overexpression of microglia and astrocytes in the hippocampus. However, pretreatment with dexmedetomidine failed to attenuate cytokine responses and activity of NF-κB, CD11b and GFAP after vagotomy or treatment with methyllycaconitine, an α-7 nicotinic acetylcholine receptor (α7nAChR) antagonist. These results suggest that pretreatment with dexmedetomidine may attenuate neuroinflammation caused by tibial fracture in rats through vagal-dependent and α7nAChR-dependent mechanisms.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou 215006, China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou 215006, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou 215006, China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Meng
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou 215006, China. Electronic address: jifuhai@126.com.
authors.forename: Fu-Hai
authors.initials: FH
authors.lastname: Ji
mesh_terms: D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D020927:Dexmedetomidine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013978:Tibial Fractures / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D053583:Interleukin-1beta; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D020927:Dexmedetomidine; D000157:Aconitine
keywords: Cholinergic receptor; Dexmedetomidine; Neuroinflammation; Tibial fracture; Vagus nerve