A putative neuroinflammatory cascade exacerbated by MIP-3α-CCR6 signaling and protected by Hsp70 in ischemic rat brains. In ischemic brains, the activation of neuroinflammatory cascades including MIP-3α-CCR6 signaling is speculated to progress as follows: astrocytes activated by proinflammatory cytokines like IL-1β and TNFα stimulate MIP-3α release. MIP-3α activates microglia through CCR6 and the cells produce other stress-related proteins like iNOS and IL-1β. Production of IL-1β further accelerates astrocyte activation. The self-perpetuating neurotoxicity cascade may damage surrounding neurons and brain tissues. On the other hand, hypothermia suppresses the cytokines and chemokines production in part by direct inhibition of NF-kB transcription via decreased IkB kinase activity. Our experiment has also elucidated the potential effect of hypothermia, which stimulated Hsp70 production in MCAO brains. Accumulated Hsp70 may inhibit NF-kB transcription by directly interacting with the NF-kB:IkB complex in astrocytes and microglia.
