Effects And Mechanism Of Propofol On The Cognitive Function In Aged Rats After Chronic Cerebral Ischemia

Objective To investigate the effects of propofol on learning and memory in aged rats after chronic cerebral ischemia. Methods Aged SD rats randomized 4 groups(n=20), pseudooperation group(Con), chronic cerebral ischemia group(VD), P₁ groups and P₂ groups. The rats in Con group received operation but the vessel are not occlusive and the rats in others received the operation of two-vessel occlusion. After operation, the rats in P₁ group and P₂ group received intraperitoneal propofol 10mg/kg/12h or 50mg/kg/12h in 2.5 ml NS for 7 days and the rats in others only received intraperitoneal 2.5 ml NS. On the 3^rd day after the last injection, 10 rats in each group received Morris water maze experiment. After Morris water maze experiment, 5 rats in each group were killed by cervical dislocation. The hippocampi were removed and sliced (450μm thick). Schaffer lateral branch in CA1 region was simulated to record LTP in CA1 region. On the 33^rd day after the last injection, repeat the experiment in the rest rats. Result 1) The achievement of the rats in VD group was lower than that of the rats in Con group both on the two experiment(P< 0.05); 2) The achievement of the rats in P₁ group was lower than that of the rats in VD group on the 3^rd day experiment(P< 0.05); There was no difference between P₁ group and VD group on the 33^rd day experiment (P > 0.05); 3) The achievement of the rats in P₂ group was lower than that of the rats in VD group both on the two experiments(P< 0.05). Conclusion The results show that chronic cerebral ischemia can restrain the learning and memory in aged rats; Low dose propofol can restrain the recently learning and memory but not restrain the long-dated learning and memory in aged rats after chronic cerebral ischemia; High dose propofol can restrain not only the recently learning and memory, but also long-dated learning and memory in aged rats after chronic cerebral ischemia. Objective To investigate the effects of propofol on the reactivity of AchE, NMDAR and GABAR in the hippocampus of aged rats after chronic cerebral ischemia. Methods Aged SD rats randomized 4 groups(n=5), pseudooperation group(Con), chronic cerebral ischemia group(VD), P₁ groups and P₂ groups. The rats in Con group received operation but the vessel are not occlusive and the rats in others received the operation of two-vessel occlusion. After operation, the rats in P₁ groups and P₂ group received intraperitoneal propofol 10mg/kg/12h or 50mg/kg/12h in 2.5 ml NS for 7 days and the the rats in others only received intraperitoneal 2.5 ml NS. On the 7^rd day after the last injection, the rats in each group were killed by cervical dislocation. The hippocampi were removed and determined the activity of AchE, NMDAR and GABAR. Result 1) About the activity of AchE: It was higher in VD group than that in Con group(P < 0.05). Both in P₁ group and P₂ group, the activity of AchE have not difference with that in VD group; 2) About the activity of NMDAR: The B_max of NMDAR in VD group was lower than that in Con group(P < 0.05). The B_max of NMDAR in P₁ group was higer than that in VD group(P < 0.05). The B_max and K_D of NMDAR in P2 group were lower than those in VD group(P < 0.05). 3) About the activity of GABAR: The B_max and K_D of GABAR in VD group were lower than those in Con group(P < 0.05). The B_max of GABAR in P₁ group was higer than that in VD group(P < 0.05). The B_max and K_D of GABAR in P₂ group were lower than those in VD group(P < 0.05). Conclusion The effect of chronic cerebral ischemia restraining the learning and memory in aged rats is related to the change of activity of AchE, NMDAR and GABAR; The mechanism of propofol restraining the learning and memory in aged rats after chronic cerebral ischemia is related to the change of activity of NMDAR and GABAR . Objective To investigate the effects of propofol on neurogenesis in the dentate gyrus of hippocampus in aged rats after chronic cerebral ischemia. Methods Aged SD rats randomized 4 groups(n=12), pseudooperation group(Con), chronic cerebral ischemia group(VD), P₁ groups and P₂ groups. The rats in Con group received operation but the vessel are not occlusive and the rats in others received the operation of two-vessel occlusion. After operation, the rats in P₁ groups and P₂ group received intraperitoneal propofol 10mg/kg/12h or 50mg/kg/12h in 2.5 ml NS for 7 days and the the rats in others only received intraperitoneal 2.5 ml NS. After the last injection, all the rats are received intraperitoneal BrdU 50mg/kg/12h for 2.5 days. On the 10^th day and 40^th day after the operation, 6 rats in each group were killed by cervical dislocation. The number of BrdU-labelled cells and Double-labelled cells in the dentate gyrus of hippocampus was counted by immunochemisty. Result 1) About the number of BrdU-labelled cells on the 10^th day after the operation: The number of BrdU-labelled cells in VD group was more than thats in Con group(P< 0.05). The number of BrdU-labelled cells in P₁ group was more than thats in VD group(P < 0.05). The number of BrdU-labelled cells in P₂ group was less than thats in VD group(P < 0.05). 2)About the Double-labelled cells on the 40^th day after the operation:There were some Double-labelled cells in each group. Conclusion The results show that chronic cerebral ischemia can stimulate neurogenesis in the dentate gyrus of hippocampus in aged rats; Low dose propofol can stimulate neurogenesis in the dentate gyrus of hippocampus in aged rats after chronic cerebral ischemia; High dose propofol can restrain neurogenesis in the dentate gyrus of hippocampus in aged rats after chronic cerebral ischemia; A small part of the new neurons can differentiate into mature neurons. Objective To investigate the mechanism of propofol effect on neurogenesis in the dentate gyrus of hippocampus in aged rats after chronic cerebral ischemia. Methods Aged SD rats randomized 4 groups, pseudooperation group (Con), chronic cerebral ischemia group(VD), P₁ groups and P₂ groups. The rats in Con group received operation but the vessel are not occlusive and the rats in others received the operation of two-vessel occlusion. After operation, the rats in P₁ group and P₂ group received intraperitoneal propofol 10mg/kg/12h or 50mg/kg/12h in 2.5 ml NS for 7 days and the the rats in others only received intraperitoneal 2.5 ml NS. On the 7^rd day after the last injection, the rats in each group were killed by cervical dislocation. The hippocampi were removed and determined the content of cAMP and the expression of BDNF, TrKB and pCREB. Result l)The content of cAMP and the expression of BDNF, TrKB and pCREB are higher in VD group than those in Con group(P < 0.05). 2) The content of cAMP and the expression of BDNF, TrKB and pCREB in P₁ group are higher than those in VD group(P < 0.05). 3) The content of cAMP and the expression of BDNF, TrKB and pCREB in P₂ group are lower than those in VD group(P< 0.05). Conclusion The mechanism of propofol effect on neurogenesis in the dentate gyrus of hippocampus in aged rats after chronic cerebral ischemia is related to the change of the expression of BDNF, TrKB and cAMP-CREB.