Enhanced activation of spinal CaMKIIα was suppressed by inhibiting CaMKIIα (by KN93) or knocking down CaMKIIα (by siRNA) in EAE mice. Lumbar spinal cord samples were collected to determine CaMKIIα activity (pCaMKIIα levels), which was elevated in EAE mice. A, Prophylactic KN93 treatment (45 nmol, i.t., daily; sampled on Day 8). B, Acute treatment with KN93 (45 nmol. i.t. at time 0, sampled at 2 h). C, Repeated treatment with CaMKIIα siRNA (2 μg, i.t., twice daily; sampled on Day 8), significantly reduced the enhancement of CaMKIIα activation. Data are expressed as the mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001 compared with the sham immune group; #p < 0.05, ##p < 0.01 compared with the saline-treated EAE group.