Sustained Baclofen-Induced Activation of GABAB Receptors After Cerebral Ischemia Restores Receptor Expression and Function and Limits Progressing Loss of Neurons

One important function of GABA B receptors is the control neuronal activity to prevent overexcitation and thereby excitotoxic death, which a hallmark cerebral ischemia. Consequently, sustained activation with selective agonist baclofen provides neuroprotection in vitro vivo models However, conditions severely downregulate receptors, would compromise neuroprotective effectiveness baclofen. On other hand, recent work suggests that stabilizes receptor expression. Therefore, we addressed question whether reduces downregulation under preserves receptor-mediated inhibition. In cultured neurons subjected oxygen glucose deprivation (OGD), mimic ischemia, were downregulated. Treatment cultures after OGD restored expression reduced loss neurons. Restoration was due enhanced fast recycling OGD-induced sorting lysosomal degradation. Utilizing middle artery occlusion (MCAO) mouse model verified severe affected cortex partial restoration systemic injection Restored recovered currents, normalized excitability observed MCAO limited progressive These results suggest baclofen-induced basis for an ischemic insult. Since regulate multiple beneficial pathways, they are promising targets strategy acute