Fig. 7

“Astrocyte-TSP2-α2δ1” pathway contributes to synaptic alteration following RI/R. RI/R switches astrocytes from “resting” to “activated”. The activated astrocytes may up-regulate and secret thrombospondin 2 (TSP 2) to bind to α2δ1, a subunit of voltage-gated calcium channels on neuronal membrane, to induce synaptic remodeling. Specifically, the EGF-like domain of TSP2 to the VWF-A domain of α2δ-1 to cause a conformational change in the molecule from closed to open. The activated α2δ-1 recruits an unidentified signal partner to combine to a “signaling complex” [56]. Then, the C terminus of α2δ-1 triggers intracellular signaling via GEFs to stimulate GTP binding to Rac1, promoting actin reorganization to facilitate spine maturation/synaptic remodeling [53]. In addition, TSP2 modulates the reorganization of the ECM by interacting with TGF-β1 and regulating the balance between MMPs and TIMPs, which provide the necessary extracellular space for synaptic remodeling [56].