Fig. 6

Protective effects of M3BIM on the closure time according to the PFA-100 analysis and thrombotic platelet plug formation in the mesenteric venules of mice, and middle cerebral artery occlusion (MCAO)-induced cerebral infarction in mice. (a) Shear-induced platelet plug formation in whole blood was determined by recording the (a) closure time of collagen/ADP (CADP) and (b) closure time of collagen/epinephrine (CEPI) as described in the Methods. (b) The mice were administered an intravenous bolus of a solvent control (0.5 % DMSO) or M3BIM (12 or 24 mg/kg), and the mesenteric venules were irradiated to induce microthrombus formation (occlusion time, a). Microscopic images (×400 magnification) of the solvent control- and M3BIM (24 mg/kg)-treated groups were recorded at 5 and 350 s after irradiation (b). The arrow indicates platelet plug formation. (c) Digital photographs (a) and dose–response bars (b) show the infarct region in brain sections stained with 2 % TTC 24 h after MCAO. Mice were injected with the solvent control or M3BIM (12 or 24 mg/kg, i.p.) before the onset of MCAO, and the infarct volume was compared with that of the sham group, as described in the Methods. The infarct volumes are expressed as a percentage of the contralateral hemisphere. Data (a-c) are presented as means ± SEM (A, n = 6; B-C, n = 8). * P < 0.05 and *** P < 0.001, compared with the DMSO group (a and b) or the sham group (c); ###P < 0.001, compared with the DMSO group (c)