FIGURE 6.

Molecular and cellular changes in the blood-brain barrier around brain abscess. Bacteria and other microorganisms in brain abscess release PAMPs that are recognized by TLR2 on astrocytes and microglia. Activation of TLR2 receptors leads to increased expression of various cytokines and chemokines, including TNF-α, IL-1β, IL-12, and MIP-2. These pro-inflammatory molecules increase the expression of adhesion molecules such as ICAM-1 and VCAM-1 that interact with integrins (LFA-1 and VLA-4) on immune cells and thus potentiate the transfer of leukocytes across the BBB. The pro-inflammatory molecules, as well as ROS, lead to increased expression and activation of matrix metalloproteinases resulting in disruption of TJ proteins. The formation of ROS is potentiated by metal ions, mainly potassium, zinc, and copper, that are released from the abscess. Moreover, decreased expression of TJ proteins such as claudin-5 and occludin is also potentiated by increased expression of VEGF from reactive astrocytes.