• Michael Haile, Alex Bekker, Richard Kline, Angela R Kamer, Samuel M Galoyan, and Allal Boutajangout.
• Department of Periodontics and Implant Dentistry, New York University College of Dentistry, New York University Medical Center, New York, USA. ark5@nyu.edu
• Eur J Anaesthesiol. 2012 Jul 1;29(7):332-7.

ContextSurgery-induced neuroinflammation has been implicated in the development of postoperative cognitive dysfunction (POCD).ObjectiveTo test the hypothesis that meloxicam, a selective cyclooxygenase (COX)-2 inhibitor, preserves postoperative cognitive function and inhibits surgery-induced neuroinflammation in a mouse model.DesignA mouse model of splenectomy-induced inflammation.MethodsSixty 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.InterventionAnimals 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.Main Outcome MeasuresShort-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.ResultsCompared 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.ConclusionThese 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.

25 keywords...

hide…