To induce TBI, male ApoE−/− mice were anesthetized with 2% isoflurane and placed in a stereotactic frame (Kopf,Tujunga,CA, USA) as previously described9,10. Briefly, a 5 mm circular craniotomy, centered near the bregma, was made and then a controlled cortical impact (CCI) was delivered to the midline at an impact speed of 3.00 m/s, tissue displacement of 1.1 mm, and impact duration of 50 ms. Following impact, the circular bone fragment from the craniotomy was glued back to the cranial window. The sham procedure was identical except for the delivery of the CCI.