Fig. 8

NMDA receptors and l-type Ca²⁺ channels can regulate CXCL12 induced neuronal death upstream of p38 MAPK activation. Activity of p38 MAPK (phosphorylation indicated by p) increases above baseline levels (upward arrow) as a critical mediator of CXCR4-mediated neurotoxicity of CXCL12. The present study implicates besides NMDAR-gated ion channels for the first-time l-type Ca²⁺ channels (l-type CC) in CXCL12 neurotoxicity as the blockade of both independently can prevent CXCL12 neurotoxicity while concomitantly preventing an increase (nimodipine; equal sign) or reducing (MK-801; downward arrow) the activity of p38 MAPK compared to baseline