Figure 4.

The time course of BBB opening and associated expression of pro-inflammatory mediators of BBB damage. Initial opening of the BBB is likely caused, at least in part, by increases in MMPs, specifically MMP-2. This initial phase occurs over ~24 h and is referred to as “reversible.” Over time, continuous production of pro-inflammatory molecules, such as TNF-alpha, IL-1beta, and MMPs 3 and 9, can lead to prolonged opening (72+ h) of the BBB, potentially contributing to long-term tissue damage. This phase is thus referred to as “irreversible.” Reprinted from Yang and Rosenberg, “Matrix metalloproteinases as therapeutic targets for stroke,” Brain Research, 2015, 1,623:30–38, with permission from Elsevier.