title: Meloxicam improves object recognition memory and modulates glial activation after splenectomy in mice.
abstract: BACKGROUND
  Surgery-induced neuroinflammation has been implicated in the development of postoperative cognitive dysfunction (POCD).
  
  
  OBJECTIVE
  To test the hypothesis that meloxicam, a selective cyclooxygenase (COX)-2 inhibitor, preserves postoperative cognitive function and inhibits surgery-induced neuroinflammation in a mouse model.
  
  
  METHODS
  A mouse model of splenectomy-induced inflammation.
  
  
  METHODS
  Sixty Swiss Webster male mice (6-8 week old) were randomised into six groups that underwent splenectomy. Animals in groups 1-4 were tested once on day 1, 5, 9 or 14 to determine the time course of delayed transient cognitive dysfunction associated with splenectomy. Animals in groups 5 and 6 were tested once on day 5 or 9 to determine the ability of the NSAID meloxicam to attenuate cognitive dysfunction.
  
  
  METHODS
  Animals in groups 1-4 received one dose 500 μl intraperitoneal physiological saline 24 h after splenectomy. Animals in groups 5 and 6 received one dose of intraperitoneal meloxicam (60 mg kg in 500 μl saline) 24 h after splenectomy.
  
  
  METHODS
  Short-term working memory as determined by Object Recognition Test (ORT) index on days 1, 5, 9 and 14 was the first main outcome. Tomato lectin staining histochemistry of glial cells was assessed on days 1, 5, 9 and 14 as a second main outcome.
  
  
  RESULTS
  Compared with day 1 (group 1), the mean ORT indices at day 5 (group 2) and day 9 (group 3) were decreased by 27.5% [95% confidence interval (CI): 0.9 to 54.1%, P = 0.04] and 23.8% (95% CI, 4.3 to 51.9%, P = 0.09), respectively. At day 5 (group 5) and day 9 (group 6), the ORT indices in the meloxicam groups were reduced by 6.6% (95% CI: -11.4 to 24.5%) and 4.3% (95% CI: -25.3 to 34.0). Thus, the administration of meloxicam attenuated the decrease in ORT indices (P = 0.031). Histochemical staining with tomato lectin showed features of microglia activation at day 5 and 9, which was reduced by the administration of meloxicam.
  
  
  CONCLUSIONS
  These findings suggest that COX-2-dependent mechanisms may play a role in the development of POCD. This effect may be dependent on the modulation of glial cell activation.
authors.affiliation: Department of Periodontics and Implant Dentistry, New York University College of Dentistry, New York University Medical Center, New York, USA. ark5@nyu.edu
authors.forename: Angela R
authors.initials: AR
authors.lastname: Kamer
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Galoyan
authors.forename: Michael
authors.initials: M
authors.lastname: Haile
authors.forename: Richard
authors.initials: R
authors.lastname: Kline
authors.forename: Allal
authors.initials: A
authors.lastname: Boutajangout
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Li
authors.forename: Alex
authors.initials: A
authors.lastname: Bekker
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007249:Inflammation; D008297:Male; D000077239:Meloxicam; D008568:Memory; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D021641:Recognition, Psychology / Q000187:drug effects; D013156:Splenectomy / Q000379:methods*; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D016861:Cyclooxygenase Inhibitors; D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; D000077239:Meloxicam