Fig 1.
MB reduces infarct volume and CBF deficit.
(A) Representative ADC, CBF and T2 maps, (B) lesion volumes, and (C) CBF value (normalized against the value at contralateral hemisphere) from three regions of interest (insets) at multiple time points post-occlusion of the vehicle and MB groups. The ROIs included: (ROI-A) the perfusion-diffusion mismatch area typically salvaged by reperfusion, (ROI-B) the perfusion-diffusion mismatch area typically not salvaged by reperfusion, and (ROI-C) the ischemic core. The ROIs and arrows delineated the regions of abnormalilties. Values are mean±SEM, n = 5 in each group. *p<0.05 indicates statistical difference from data at 30 mins.
Fig 2.
MB reduces behavioral deficits.
(A) Neurological scores and (B) Foot fault scores of the MB group (n = 5) and the vehicle group (n = 5) 24hrs after MCAO. Values are mean±SEM.
Fig 3.
MB’s affects on autophagic and apoptotic markers 24hrs after stroke.
Western blot analysis of autophagic marker LC3-II/I ratio, and apoptotic marker Caspase-3 in sham, vehicle and MB groups. The ratio of expression levels of LC3-II/I (B) were significantly increased in ROI-A and ROI-B of MB treated group compared to that of vehicle group (#p<0.05). Caspase-3 expression level (C) was significantly increased in ROI-A and ROI-B of MB treated group compared to that of vehicle group (#p<0.05). *p<0.05 indicates statistical difference from sham. Values are mean±SEM, n = 5 in each group.
Fig 4.
Western blots of p53, Bcl-2 and Bax 24hrs after stroke in the same ROI of the sham, vehicle and MB group.
*p<0.05 indicates statistical difference from sham. #p<0.05 versus vehicle in same ROI. Values are mean±SEM, n = 5 in each group.
Fig 5.
(A) Western blots of AMPK through the hyper-phosphorylated of AMPKα at Thr172 site and AMPKβ1 at Ser108 site 24hrs after stroke of vehicle and MB group. (B) Western blots of phosphorylation level of TSC2 at site Ser1387 and mTOR at site Ser2448 24hrs after stroke of vehicle and MB group. *p<0.05 indicates statistical difference from sham. #p<0.05 versus vehicle in same ROI. Values are mean±SEM, n = 5 in each group.
Fig 6.
A schematic illustration of the effect of MB on the inhibition of apoptosis and induction of autophagy.
MB induces neuroprotection in neurons following cerebral ischemia through both the apoptotic p53-Bcl-2-Bax signaling pathway and autophagic p53-AMPK-TSC2-mTOR signaling pathway. The arrows show the effect of MB on these pathways.