Fig. 5

Pretreatment with intranasally delivered recombinant human MANF decreases infarct volume and promotes behavioral recovery after stroke. a Timeline of the experiment. The black arrows indicate the intranasal administration of rhMANF or vehicle. RhMANF or PBS was administered to the rats 3 times: 12 h before a 60-min dMCAo, immediately before dMCAo and immediately after reperfusion. The total MANF dose was 20 µg or 60 µg. dMCAo = distal middle cerebral artery occlusion, B = behavioral assay, TTC = 2,3,5-triphenyltetrazolium chloride staining. b Infarction volume was determined 2 days after dMCAo by TTC staining, n = 19–25 per group, (*p < 0.05), Student’s t-test. c Distribution of infarction along the rostrocaudal axis, n = 19–25 per group. d Representative images of TTC stained brain sections from the vehicle and rhMANF groups. e RhMANF treatment had no effect on cortical cerebral blood flow (CBF). CBF was measured with laser Doppler flowmetry before ischemia, during ischemia (dMCAo) and after reperfusion. Rats received intranasal rhMANF (n = 10) or vehicle (n = 9) immediately before CBF measurement. f Body asymmetry test, g Bederson’s score, h horizontal activity, i vertical activity, and j body weight at different time points after 60-min dMCAo in vehicle (n = 14) and rhMANF (n = 15) treated rats. The total MANF dose was 20 µg. In f–g (***p < 0.001) indicate comparison between vehicle and rhMANF groups with Mann–Whitney U test, corrected for multiple comparisons. The values are expressed as mean ± SD