IMR Press / FBS / Volume 3 / Issue 4 / DOI: 10.2741/222

Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Interaction of free radicals, matrix metalloproteinases and caveolin-1 impacts blood-brain barrier permeability
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1 School of Chinese Medicine, The University of Hong Kong, Hong Kong SAR, China
2 Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
3 Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong SAR, China

*Author to whom correspondence should be addressed.


Front. Biosci. (Schol Ed) 2011, 3(4), 1216–1231;
Published: 1 June 2011

Free radicals play an important role in cerebral ischemia-reperfusion injury. Accumulations of toxic free radicals such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) not only increase the susceptibility of brain tissue to ischemic damage but also trigger numerous molecular cascades, leading to increased blood-brain barrier (BBB) permeability, brain edema, hemorrhage and inflammation, and brain death. Activating matrix metalloproteinases (MMPs) is a key step in BBB disruption. MMPs are proteolytic zinc-containing enzymes responsible for degradation of the extracellular matrix around cerebral blood vessels and neurons. Free radicals can activate MMPs and subsequently induce the degradations of tight junctions (TJs), leading to BBB breakdown in cerebral ischemia-reperfusion injury. Recent studies revealed that caveolin-1, a membrane integral protein located at caveolae, can prevent the degradation of TJ proteins and protect the BBB integrity by inhibiting RNS production and MMPs activity. The interaction of caveolin-1 and RNS forms a positive feedback loop which provides amplified impacts on BBB dysfunction during cerebral ischemia-reperfusion injury. Here, we reviewed the recent progress in the interactions of RNS, caveolin-1 and MMPs. Current evidence indicates that the interactions of RNS, caveolin-1 and MMPs are critical signal pathways in BBB disruption and infarction enlargement during cerebral ischemia-reperfusion injury.

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