FIGURE 1.

Specific deletion of Nhe1 in Cx3cr1-Cre^ER;Nhe1^f/f mice had no effects on acute ischemic infarct formation but significantly improved neurological functions after ischemic stroke. (a) Experimental protocol. Either corn oil (3.75 ml/kg) or tamoxifen (Tam, 75 mg/kg body weight, 20 mg/ml in corn oil, i.p.) was administered daily for consecutive 5 days in Cx3cr1-Cre^ER;Nhe1^f/f mice at postnatal day 30–40 (P30–40). A 30-day waiting period was given for complete clearance of Tam and peripheral Cx3cr1⁺ monocyte turnover. At P65–75, transient focal cerebral ischemia in mice was induced by 50 min of middle cerebral artery occlusion (tMCAO). 2,3,5-Triphenyltetrazolium chloride (TTC) staining was conducted at 48 hr reperfusion (Rp). Ex vivo DTI imaging was conducted at 14 days Rp. Immunostaining was conducted at 3 and 14 days Rp. Flow cytometry experiments were conducted at 0 (baseline), 3, 7, and 14 days Rp. Behavioral tests were conducted at 1 day prior to tMCAO, and at 1, 2, 3, 5, 7, 10, and 14 days Rp. (b) TTC staining of the oil- or Tam-treated Cx3cr1-Cre^ER;Nhe1^f/f mice at 48 hr Rp. (c and d) Infarct volume and brain swelling in mice at 48 hr Rp with TTC staining. Data are mean ± SEM. N = 4–6. (e) Neurological score of mice after tMCAO. Data are mean ± SEM. N_Tam = 10 (5 males, 5 females) and N_Oil = 6 (1 male, 5 females). *p < .05, **p < .01, oil- versus Tam-treated groups. (f-i) Corner test, adhesive contact test, adhesive removal test, and rotarod accelerating test of the same cohort of mice in e. Data are mean ± SEM. *p < .05, ***p < .001, oil- versus Tam-treated groups. (j) Survival curve of the same cohort of mice in e. Data are mean ± SEM. *p < .05, oil- versus Tam-treated groups [Color figure can be viewed at wileyonlinelibrary.com]