The blood brain barrier (BBB) is a continuous, non-fenestrated vessel system that tightly
regulates the movement of molecules, ions, and cells between the blood and the central nervous system.
Endothelial cells are the major constituents of the BBB and these cells are linked to each other through
intercellular contact points composed of tight junctions, adherent junctions and gap junctions. These
three types of junctions are connected to the intracellular actin cytoskeleton via various adaptor proteins.
Thus, the actin cytoskeleton plays a crucial role in regulating the stability of endothelial cell contacts
and vascular permeability. Shear stress, growth factors, and Wnt/β-catenin pathway modulators
contribute to maintaining endothelial cell integrity by controlling actin dynamics under homeostatic
conditions. Interestingly, the downstream signaling of the aforementioned factors converges at Rac1,
which mediates cortical actin stabilization, stress fiber destabilization and junctional complex stabilization
by controlling subcellular cofilin dynamics. However, Rac1 is not the only modulator of cofilin activity;
many other agents activated during inflammatory, ischemic, and excitotoxic conditions can disturb
homeostatic cofilin dynamics and induce BBB disruption. Therefore, in this review, we discuss organization
of the actin cytoskeleton in BBB endothelial cells and how interactions between the actin cytoskeleton
and junctional complexes are maintained during homeostatic conditions. Furthermore, we
discuss how an imbalance in subcellular cofilin dynamics can contribute to BBB disruption and highlight
Rac1 as a potential target that can be exploited to preserve BBB stability.