Sigma-1 receptor activation alleviates blood-brain barrier disruption post cerebral ischemia stroke by stimulating the GDNF-GFR α1-RET pathway

In this study, we investigated Sig-1R activation as a BBB integrity promoter via many post ischemic stroke pathways. Sig-1R activation in BBB-associated astrocytes can increase glia-derived neurotrophic factor (GDNF) secretion in bilateral common carotid artery occlusion (BCCAO) mice. Upregulated GDNF activates its receptors in CMECs to promote BBB integrity, and activated Sig-1R in CMECs facilitates this process. In vitro experiments have found that Sig-1R activation in CMECs promotes the interaction between the GDNF α1 receptor and transduction rearrangement gene, increasing PI3K-AKT-junction protein signaling pathway expression. Sig-1R activation could be an effective therapeutic method for preventing BBB damage in ischemic stroke and other neurological conditions.PMID:34582837 | DOI:10.1016/j.expneurol.2021.113867
Source: Experimental Neurology - Category: Neurology Authors: Source Type: research