title: Pregabalin can prevent, but not treat, cognitive dysfunction following abdominal surgery in aged rats.
abstract: OBJECTIVE
  The present study aimed to explore the preventive or therapeutic effect of peri-operative pregabalin treatment on the memory deficits and related hippocampal inflammation following surgery in aged rats.
  
  
  METHODS
  Aged rats underwent abdominal or sham surgery, and were then divided into 2 groups, either early or late pregabalin treatment. Fourteen days after surgery, the cognitive function was assessed using novel object recognition test, followed by measurement of hippocampal cytokines and voltage-dependent calcium channel α2δ subunit (CACNA2D1). The parabiotic experiments determined whether the humoral or neuronal pathway was involved in the neuroinflammation development following the abdominal surgery. The effects of pregabalin on LPS-induced cytokine release from hippocampal microglia were also evaluated.
  
  
  RESULTS
  Early pregabalin treatment, which was administered pre-operatively and continued for 3 or 7days after surgery, prevented memory deficits and decreased hippocampal pro-inflammatory cytokine levels. In contrast, no beneficial effects were observed when pregabalin was administered late in the post-operative period. The hippocampal levels of CACNA2D1 did not change under any experimental condition. The data from the cross-circulation (parabiosis) experiments indicated that abdominal surgery may induce neuroinflammation via a neural transmission pathway from the periphery to the brain. The ex vivo experiments further demonstrated that pregabalin had no effect on LPS-induced cytokines release from hippocampal microglia.
  
  
  CONCLUSIONS
  Our findings highlight reveal that peri-operative pregabalin treatment during the early post-operative period can prevent neuroinflammation and memory deficits after surgery. It is likely this occurs through a peripheral and central neuro-immune interaction rather than through direct anti-inflammatory effects.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Japan. Electronic address: takashika@kochi-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawano
authors.affiliation: Department of Dental Anesthesiology, Tokushima University School of Dentistry, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Eguchi
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Yamanaka
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tateiwa
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Japan.
authors.forename: Fabricio M
authors.initials: FM
authors.lastname: Locatelli
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Nankoku, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D000009:Abdominal Muscles / Q000601:surgery*; D000375:Aging / Q000187:drug effects* / Q000523:psychology; D000818:Animals; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D008297:Male; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D000069583:Pregabalin / Q000494:pharmacology / Q000627:therapeutic use*; D011300:Preoperative Care / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D000069583:Pregabalin
keywords: Microglia; Neuroinflammation; Post-operative cognitive dysfunction