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Leaky blood vessels open up nerve cells to toxic assault in Lou Gehrig's disease
Date:4/7/2008

Rather, the word barrier describes an elaborate molecular lattice that lines the insides of the blood vessels that weave throughout the spinal cord. The lattice controls which molecules can cross from the blood to the neurons in the spinal cord, and which cannot. Its a bit like netting with very small openings that line the inside of blood vessels.

Oxygen and many nutrients get the OK to pass through the barrier in measured amounts. And the barrier readily accepts waste products from the spinal cord, transporting them away from the central nervous system and eventually out of the body. But the netting should be taut and should bar substances in the blood that have no business being near neurons.

The team found that a SOD-1 mutation disrupted key building blocks in the barrier. Essentially, the mutations loosened the lattice, creating bigger holes in the barrier that allowed molecular interlopers to pass from the blood to the spinal cord.

Mice with the mutation had lower levels of three types of tight junction proteins that are key components of the barrier: ZO-1, occludin and claudin-5. In mice just two months old, the numbers of those important tight junction proteins in the linings of blood vessels were reduced by about half, by 40 to 60 percent, allowing the lattice to loosen abnormally.

The weakened barrier brought about several problems. Neurons were exposed directly to biochemical byproducts of hemoglobin, which forms reactive oxygen molecules that injure neurons. Where the barrier had weakened, tiny hemorrhages dotted the spinal column. The smallest blood vessels crucial to nerve health shrunk: Mice with the mutation had total capillary length in the spinal cord 10 to 15 percent less than healthy mice, and their blood flow in the spinal cord was reduced by 30 to 45 percent.

Scientists must investigate whether the same processes happen in forms of ALS that are not inherited. Zlokovic notes that from what is known s
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Contact: Tom Rickey
tom_rickey@urmc.rochester.edu
585-275-7954
University of Rochester Medical Center
Source:Eurekalert

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