Figure 3.
CBD protection against damage from BBB disruption. TBI disrupts cerebral blood flow and damages the integrity of the BBB. Hyperpermeability resulting from damaged tight-junctions and endothelial cells leads to increased inflammation and oxidative stress. (1) CBD shifts the polarization of macrophages from their pro-inflammatory M1 type to anti-inflammatory M2 type via activation of A2A adenosine receptors or by enhancing AEA-mediated CB2 receptor signaling. (2) CBD may improve BBB integrity and prevent hyperpermeability by suppressing TBI's damaging effects on tight-junction proteins via action on PPARγ and 5-HT1A receptors. (3) CBD is a potent antioxidant that reduces ROS and protects against oxidative damage to neurons and the BBB. It also reduces levels of TNF-α and other inflammatory markers that reduce the integrity of the BBB. (4) CBD may regulate cerebral blood flow to enhance reperfusion following injury via activation of GPR18, GPR55, and 5-HT1A receptors.