Dysfunction of the BBB may be in the form of increased permeability or BBB breakdown to large and small molecules in brain diseases and/or may take the form of alterations in endothelial transport mechanisms. Well documented in the literature is the increased BBB permeability to plasma proteins, which occurs in conditions associated with vasogenic edema such as ischemic and hemorrhagic stroke, infections, inflammation, seizures, trauma, tumors, epilepsy, and hypertensive encephalopathy (182, 183). Increased permeability to C14 sucrose implying increased ionic permeability has been reported in peripheral inflammatory pain (184). Increased BBB permeability to ions and plasma proteins has been reported in human and experimental diabetes (184, 185). Global vascular changes and altered expression of Pg-p have been implicated in the pathogenesis of degenerative diseases such as Alzheimer's disease (186, 187) and Parkinson's disease (188) as reviewed previously (136, 189).
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