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The BBB/Neurovascular Unit in Health and Disease

Posted: Mon Jan 03, 2011 8:47 pm
by orion98665
Very interesting article.
http://pharmrev.aspetjournals.org/content/57/2/173.full

D. Alteration of Blood-Brain Barrier Tight Junction in Disease
Failure of the BBB is a critical event in the development and progression of several diseases that affect the CNS.

1. Hypoxia/Ischemia.
Cerebral ischemia is a complex insult that involves a loss of blood flow as well as depletion of oxygen and essential nutrients (del Zoppo and Hallenbeck, 2000) and is associated with increased microvascular permeability (Kempski, 2001; Petty and Wettstein, 2001). A number of studies using in vitro models of the BBB have indicated that hypoxia and hypoxia/reoxygenation lead to increased permeability and/or disruption of BBB TJ (Abbruscato and Davis, 1999a; Fischer et al., 1999; Mark and Davis, 2002), although hypoxic stress may increase permeability via the transcellular route as well (Plateel et al., 1997; Cipolla et al., 2004). Some reports have indicated that BBB endothelial cells are less responsive to hypoxic stress when cocultured with astrocytes (Kondo et al., 1996; Fischer et al., 2000) or pericytes (Hayashi et al., 2004); nonetheless, in vivo hypoxia/reoxygenation treatment is associated with increased BBB permeability and decreased expression of occludin (Witt et al., 2003), as well as activation of the transcription factors nuclear factor-κB and hypoxia-inducible factor-1 (Witt et al., 2005). Hypoxic reorganization of BBB TJ seems to be mediated in part by vascular endothelial growth factor and nitric oxide (Fischer et al., 1999; Mark et al., 2004), and vascular endothelial growth factor antagonism reduces postischemic edema and injury in vivo (van Bruggen et al., 1999), indicating that TJ disruption is likely involved in the progression of ischemic brain injury.

Posted: Mon Jan 10, 2011 9:50 am
by Cece
I printed this out, thanks. It's a little beyond me currently.