Fig. 8: Model for the mechanism and function of ischemia-induced neuronal actinification.

(Left) In response to ischemic stress, neurons undergo osmotic swelling and an extensive, but reversible, INF2-mediated reorganization of the actin cytoskeleton, characterized by F-actin disassembly in dendritic spines and F-actin accumulation in the dendrite shaft (actinification). In the absence of INF2, neurons fail to actinify and instead undergo premature cell death. (Right) Summary of key molecular steps connecting ischemia and its excess NMDA receptor activation with INF2-mediated F-actin polymerization in the soma and dendrite. Actinification is triggered by cell swelling and requires Ca²⁺ influx and depolymerization of spine F-actin. This diagram was created with Biorender.com.