r, be havioral data indicated that SCM 198 could ameliorate cognitive impairments in a time and dose dependent man ner with 60 mg kg as the optimal dose. SCM 198 alleviated thorough microglial activation, decreased phosphorylation of ERK and tau, inhibited synaptophysin loss and NF ��B p65 activation in vivo Intrahippocampal injections of AB1 40 led to elevated ERK phosphorylation, NF ��B p65 activation, increased tau phosphorylation, and synaptophysin loss, which were significantly reversed by SCM 198 treatment in a dose dependent manner, with 60 mg kg as the optimal dose 4. 44, P 0. 0045, Figure 7d. F 13. 23, P 0. 0001, Figure 7e. F 6. 93, P 0. 0001, Figure 7f. F 6. 13, P 0. 0005, Figure 7g, respect ively.

Immunostains of brain slices against iba 1 showed that AB1 40 injections induced e cessive microglial activation at and around the injection site and SCM 198 at 60 mg kg and DON could attenuate this activation 22. 04, P 0. 0001, Figure 7h. Synergistic effects of SCM 198 Inhibitors,Modulators,Libraries and donepezil on cognitive impairments in a chronic rat AD model induced by AB1 40 As described in the Material and Methods section, 45 male rats were pretreated with vehicle, 60 mg kg SCM 198, 1 mg kg DON or co administrated with SCM 198 Inhibitors,Modulators,Libraries and DON for 7 days. Fifty days after surgery, rats of only the AB1 40 injected group showed more severe cognitive impairments in spatial reference memory as compared with that of rats of 12 day recovery from surgery. Even up to trial 8, rats of only the AB1 40 injected group still needed 37. 3 seconds in average to find the invisible platform.

No significant differences were observed from trial 1 to trail 4 1. 292, P 0. 2895. F 2. 078, P 0. 1018. F 2. 40, P 0. 066. F 2. 603, P 0. 0502, respectively, Figure 8a. From trial 5 to trial 8, therapeutic effects of SCM 198, DON and co administration of SCM and DON became sta tistically significant Inhibitors,Modulators,Libraries and animals of co administration group showed the best performances. 4. 517, P 0. 0042. F 6. 299, P 0. 0005. F 9. 255, P 0. 0001. F 12. 75, P 0. 0001, respectively, Figure 8a. Two way repeated measures ANOVA ana lysis showed an e tremely significant effect of drug treatment 21. 41, P 0. Inhibitors,Modulators,Libraries 0001 and trial effect 35. 76, P 0. 0001. Body weight remains normal and no statistical differences were found in swimming speed of rats between groups throughout the e periment. Time spent in the target quadrant was also assessed during probe trial.

Figure 8b showed that 60 mg kg SCM 198, 1 mg kg DON and co administration of SCM 198 and DON all lengthened their stay in target quadrant with rats of co administration group spending the longest time 4. 562, P 0. 004, Figure 8b indicating that SCM 198 could effectively improve the therapeutic Brefeldin_A ef fect of DON. Discussion The role neuroinflammation plays in the pathological development of AD still remains controversial today, as inflammation itself is an innate third defense against both en dogenous and e ogenous insults under normal physio logical conditions. In neurodegenerative diseases like AD,