Peripheral Surgery Model in Mice

All experiments were performed in accordance with the National Institutes of Health guidelines and regulations. The animal protocol was approved by the Massachusetts General Hospital (Boston, Massachusetts) Standing Committee on the Use of Animals in Research and Teaching. Efforts were made to minimize the number of animals used. Since it is technically difficult to perform an epidural or spinal anesthesia in mice, we have established an animal model of peripheral surgery in the abdomen under local anesthesia in mice. WT C57BL/6J mice (9 month-old, The Jackson Laboratory, Bar Harbor, ME; and 18 month-old, National Institute of Aging, Bethesda, MD), and AD Tg mice [B6.Cg-Tg(APPswe, PSEN1dE9) 85Dbo/J, 9 month-old, The Jackson Laboratory] were used in the studies. The mice were randomly assigned to a surgery or control group by weight. The mice were gently restrained to a heating pad (37 C°) using paper tape. A local anesthetic bupivacine (0.5% and 0.1 ml) was injected into the skin and subcutaneous tissue of the abdominal area. A 2.5 cm incision was made in the middle of the abdomen to open and then close the abdominal cavity in the mouse. The procedure lasted about five minutes. We did not use sedative medicine in an effort to reveal the effects of surgery alone and to minimize all other variables. EMLA cream (2.5% lidocaine and 2.5% prilocaine) was used every 8 hours for the first and second post-operative days to treat the surgery-associated pain. We did not use antibiotics because the procedure was aseptic. The non-surgery (control) mice underwent the same procedure, only without the incision. In the intervention studies, each mouse received compound E (the inhibitor of γ-secretase, which can reduce Aβ generation) (3 mg/kg, IP, Enzo Life Sciences Inc., Farmingdale, NY, Cat. Number: ALX-270-415) or saline daily for 7 days post-surgery20 (link).