MRI analysis

Brain MRI was performed using a 1.5 T MR VivoLVA scanner (DS Pharma Biomedical Co. Ltd., Osaka, Japan), and 1‐mm‐thick slices were obtained. Mice were anesthetized by 2.5% isoflurane and subsequently administered 200 μL of 20 mmol/L gadolinium‐diethylenetriamine penta‐acetic acid (Gd‐DTPA) (Magnevist; Bayer, Leverkusen, Germany) through the tail vein. After 2 min, Gd‐DTPA‐enhanced T1‐weighted images were obtained. For the quantitative analysis of Gd‐enhanced lesions, an area measuring 2 × 6 pixels was defined as the region of interest (ROI) within a Gd‐enhanced lesion. The mean intensity change for each pixel (x) was then calculated as follows: x = [(intensity of contrast‐enhanced image − intensity of precontrast‐enhanced image)/intensity of precontrast‐enhanced image] × 100. The mean values for the change in intensity were calculated for each mouse.