Fig 2: Expression of EphA4 in the hippocampal CA1 and CA3 areas following ephrin-A5-Fc intrahippocampal infusions. Mice received intrahippocampal infusions of ACSF, IgG2A isotype control, NC-ephrin-A5-Fc or C-ephrin-A5-Fc via micro-osmotic pump for 7 days, beginning 4 days following pilocarpine treatment. (A) Immunohistochemistical staining of EphA4, which appears brown. The expression of EphA4 was analyzed in the (B) CA1 and (C) CA3 areas, and was reduced by NC-ephrin-A5-Fc and increased by C-ephrin-A5-Fc. Data are expressed as the mean ± standard deviation (n=3). *P<0.05. Scale bars represent 100 µm. EphA4, ephrin receptor A4; CA, Cornu Ammonis; ACSF, artificial cerebrospinal fluid; NC, non-clustered; C, clustered.

Fig 3: Immunohistochemistical staining of ephrin-A5 in the hippocampal CA1 and CA3 areas. Samples were harvested at 7, 14, 28 and 56 days post-SE and stained for ephrin-A5. Ephrin-A5 staining appears brown. Scale bars represent 100 µm. CA, Cornu Ammonis; SE, status epilepticus; Con, control group; d, day.

Fig 4: Mean density and diameters of microvessels, and expression of EphA4 and ephrin-A5. The mean density of PECAM-1-labeled microvessels was calculated in the (A) CA1 and (B) CA3 areas. The mean diameter of PECAM-1-labeled microvessels was calculated in the (C) CA1 and (D) CA3 areas. EphA4 expression was assessed in the (E) CA1 and (F) CA3 areas. Ephrin-A5 expression was assessed in the (G) CA1 and (H) CA3 areas. The mean density and diameter of microvessels, and the expression of EphA4 and ephrin-A5, all increased post-SE compared with control groups. Data are expressed as the mean ± standard deviation (n=6). **P<0.01; ***P<0.001. EphA4, ephrin receptor A4; PECAM-1, platelet endothelial cell adhesion molecule-1; CA, Cornu Ammonis; SE, status epilepticus; Con, control group; d, day.

Fig 5: WCDD301 suppresses glucagon secretion from human α cells in both healthy and type 1 diabetic participants.Glucagon secretion from healthy human donor (n = 3) dispersed islet cells following (A) 1 hour, (B) 3 hours, or (C) 6 hours of exposure to WCDD301. Insulin secretion from healthy human dispersed islet cells following (D) 1 hour, (E) 3 hours, or (F) 6 hours of exposure to WCDD301. Each dot demonstrates values (mean ± SD) of an individual. In each panel, values (mean ± SEM) were compared with the respective controls using 1-way ANOVA; *P < 0.05, **P < 0.01, ***P < 0.001. Secretion of glucagon in vehicle-treated (C, control) cells and cells treated with Ephrin-A5 Fc (E) or WCDD301 in (G) isolated islets and (H) dispersed islet cells of 2 donors with T1D. Secretion of insulin in (I) isolated islets and (J) dispersed islet cells of the donors with T1D. Each dot demonstrates mean values of the selected islets or dispersed islet cells for each subject. In each panel, values (mean ± SEM) were compared with the respective controls based on the level of changes. *remarkable changes of P < 0.05.