Breaking Down a Barrier

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Science  02 May 2014:
Vol. 344, Issue 6183, pp. 451
DOI: 10.1126/science.344.6183.451-b

Ischemic stroke, one of the most common causes of death and disability, occurs when a blood vessel supplying oxygen and nutrients to the brain becomes obstructed. Besides injuring brain cells, a stroke disrupts the function of endothelial cells in the blood-brain barrier (BBB), which exacerbates brain damage. The cellular mechanisms underlying BBB breakdown during a stroke are poorly understood. To study this, Knowland et al. created transgenic mice expressing a fluorescent reporter gene in endothelial cells and then, with the help of fluorescent dyes, used two-photon microscopy to image BBB function in the mice after an experimentally induced stroke. In contrast to a prevailing theory emphasizing the primary role played by a diffusion barrier called the tight junction, the imaging study revealed that the initial cause of BBB breakdown (occurring 6 hours after the stroke) was aberrant up-regulation of transcytosis, a process by which molecules are transported across the endothelial cell. It was not until 24 to 48 hours after the stroke that tight junctions showed structural defects. Understanding this sequence of events may lead to therapies that limit the brain damage caused by a stroke.

Neuron 10.1016/j.neuron.2014.03.003 (2014)

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