December 13, 2007
ALS Mice Lack Normal Blood-Spinal Cord Barrier
Scientists at the University of South Florida at Tampa and Johnnie B. Byrd’s Alzheimer Center and Research Institute in that city say a barrier that normally exists between the spinal cord and the bloodstream is disrupted in mice with amyotrophic lateral sclerosis (ALS), and that its loss could play an important role in causing or exacerbating nerve-cell death in this disease.
Svitlana Garbuzova-Davis at USF and colleagues, who published their findings online Nov. 21 in PLoS (Public Library of Science) One, compared 14 ALS-affected mice with six unaffected mice on measures of motor function and of integrity of a barrier between the spinal cord and blood circulation. (The ALS-affected mice had a genetic form of ALS that also affects 1 percent to 3 percent of humans with the disease.)
When they injected a blue dye into a vein in the unaffected mice at 12-13 weeks or 19-20 weeks of age, it stayed in the bloodstream. But when they injected the same dye into a vein in 13-week-old mice with early-stage ALS, they saw that a considerable amount of it had leaked into the spinal cord. When they examined late-stage ALS-affected mice, injected with the dye at 17-18 weeks old, the leakage into the cord was even greater.
In an earlier study, published in July in Brain Research, Garbuzova-Davis’ group noted damage to barriers in the brain and spinal cord of ALS-affected mice when they examined blood vessels with an electron microscope.
The researchers write that the damage to the muscle-controlling nerve cells known as motor neurons, the hallmark of ALS, could be accelerated if leaky blood vessels are allowing large molecules, such as immune-system proteins known as immunoglobulins, to enter the nervous system.
On the other hand, processes that start in the nervous system, such as inflammation or the loss of small cells that normally have footlike appendages pressed up against the blood vessels, could be causing the vessel leakiness, they say.
“Importantly,” they write, “is BSCB [blood-spinal cord barrier] breakdown a primary or secondary mechanism to motor neuron degeneration in [ALS-affected] mice?” If future studies demonstrate that disruption of the blood-spinal cord barrier occurs before any disease symptoms or other signs of ALS appear, it would indicate that such disruption “plays a primary role in ALS pathogenesis.”
