In summary, the upregulation of RACK1 following brain contusion exerted neuroprotective effects against secondary brain injury, which were probably mediated by activation of the IRE1-XBP1 pathway.; Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion. After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent.;BDNF-dependent neurite outgrowth was significantly attenuated in Xbp1(-/-)  neurons. These findings suggest that BDNF initiates UPR signaling in neurites and that Xbp1, which is activated as part of the UPR, conveys the local information from neurites to the nucleus, contributing the neurite outgrowth.;Hence, our findings reveal that XBP1s is neuroprotective through a mechanism that engages Kal7 pathway with therapeutic implications in AD pathology.;Using this in vivo model, we now show that ER stress is induced early in EAE and that modulation of ER stress by inhibition of eIF2a-CHOP and activation of XBP-1 in RGC specifically, protects RGC somata and axons and preserves visual function.