Objective To explore the effect of PGE1 on the cognitive impairment and the expression of VEGF and BDNF in the hippocampus after bilateral common carotid artery occlusion in adult rats. Methods Forty-eight rats were randomly divided into PGE1 group (10μg·kg-1·d-1, iv), PGE1+VEGFR antagonist group (PGE1, 10μg·kg-1·d-1, iv;SU5416, 25 mg·kg-1·d-1, ip), saline group and sham group (n=12 each). Morris Water Maze test (MWM) was used to examine cognitive function in rats. Drugs and saline were given to VD rats at 24 d for 7 consecutive days following opera?tion. Half of the rats in each group were sacrificed for Western Blot at 6 days after MWM test. Western Blot was conduct?ed to examine the relative expression levels of VEGF and BDNF in the hippocampus. Results Compared to saline and PGE1+VEGFR antagonist groups, the escape latency in PGE1 group was shorter (P<0.05), and the times that rats swam across the platform location and time percentage in previous platform quadrant in PGE1 group was longer (5.77±0.83 vs.2.88 ± 0.47 vs. 2.63 ± 0.44, P<0.01;32.28%± 4.56%vs. 20.42%± 5.50%, 23.08%± 5.06%, P<0.05). Compared with saline group and sham group, PGE1 group had higher levels of VEGF (0.057±0.005 vs. 0.038±0.002 vs. 0.027±0.002, P<0.05) and BDNF (0.481±0.049 vs. 0.339±0.021 vs. 0.224±0.04, P<0.05). but the increase in VEGF expression in PGE1 group was no significant (0.057±0.005 vs. 0.053±0.003, P>0.05) compared with PGE1+VEGFR antagonist group, while the aug?ment of BDNF in PGE1 group was remarkable (0.481±0.049 vs. 0.373±0.034, P<0.05). Conclusions PGE1 can upregu?late VEGF and BDNF expression and modify cognitive impairment in VD rats, while the effects of PGE1 on cognitive function and BDNF expression can be partially blocked by VEGFR antagonist SU5416.

Objective To investigate the roles of neutral sphingomyelinase-2 (nSMase2) pathway on cerebral edema and cerebral injury in cerebral ischemia-reperfusion injury in rats. Methods Seventy-six adult male SD rats were randomly divided into sham operation group (n = 12), modeling group (n = 16), vehicle group (n = 16), SB203580 (a p38 mitogen activated protein kinase [MAPK] inhibitor) treatment group (n = 16) , and MRS1754 (a selective adenosine A2B receptor [A2B AR] antagonist) treatment group (n = 16) according to the random number table. A suture-occluded method was used to induce a middle cerebral artery ischemia-reperfusion model. Vehicle, SB203580, and MRS1754 were injected into the lateral ventricles 30 min before model preparation, the neurological function score was performed after ischemia-reperfusion for 24 h. 2,3,5 triphenyltetrazolium staining was used to detect the infarct volume. The water content of brain tissue was detected by dry-wet weight method. Western blot analysis was used to detect the expression of nSMase 2 and p38 MAPK in ischemic brain tissue. Immunohistochemical staining was used to detect the expression of nSMase 2 in ischemic brain tissue. Results MRS1754 significantly decreased neurobehavioral score (P < 0. 05) and reduced cerebral infarction volume (P < 0. 05) in rats. Both MRS1754 and SB203580 significantly decreased the water content of ischemic brain tissue (all P < 0. 05). In addition, MRS1754 also significantly decrease the phosphorylation of p38 MAPK after ischemia-reperfusion and decreased the expression level of nSMase 2 (P < 0. 01). Conclusion Regulation of A2BAR and p38 MAPK of nSMase upstream may play a neuroprotective role after cerebral ischemia-reperfusion injury.