TrkB receptor antagonist ANA-12 blocks the anti-PSD effects of TP-500. Mice were treated with TP-500 (2 mg/kg) on day 7 post-ICH and then once daily until the experiment ended. ANA-12 (0.5 mg/kg) was administered on day 14 post-ICH and continued daily until the end of the experiment. (a) Flow chart illustrates the timing of the experimental protocol. i.p., intraperitoneal. (b) TP-500 treatment significantly reduced immobility time on the forced swim test and on the tail suspension test and increased preference for sweetened drinking water after c-ICH. These changes were abolished by concurrent administration of ANA-12. n = 8 male mice per group. Values are mean ± SD; *p < 0.05 for TP-500 & ANA-12 vs. TP-500 & vehicle. (c) Western blots show that the TP-500–induced increase in protein expression of Nrf2 and BDNF on day 28 after c-ICH was not attenuated by concurrent administration of ANA-12. n = 6 male mice per group. Values are mean ± SD; n.s., not significant. (d) The mRNA expression levels of CD86, a pro-inflammatory marker for microglia/macrophages, and CD206, an anti-inflammatory marker, in brain tissue on day 28 after c-ICH. n = 5–6 male mice per group. (e) Immunostaining showed the colocalization of Iba-1+ microglia/macrophages and pro- inflammatory factor iNOS in different groups on day 28 after c-ICH. Scale bar = 50 μm. n = 5–6 male mice per group. Values are mean ± SD. *P < 0.05 TP-500&ANA-12 vs. TP-500&vehicle group. #P < 0.05 TP-500&vehicle vs. c-ICH group.