Researchers find blood-brain barrier damaged by disease

March 8, 2011, University of South Florida

A study into the effects of Sanfilippo Syndrome type B (MPS III B) has found that the barrier responsible for protecting the brain from the entry of harmful blood-borne substances is structurally and functionally damaged by the devastating disease. University of South Florida researchers identified damage in specific brain structures involved in the pathology of MPS III B, one of four Sanfilippo syndromes, all of which are inherited diseases of metabolism.

The study, using a of MPS III B, has been published online in the journal . Before this study, little was known about the integrity of the blood-brain barrier in this disease.

"These new findings about blood-brain barrier structural and in MPS III B mice, even at early disease stage, may have implications for and should be considered in the development of treatments for MPS III B," said study lead author Svitlana Garbuzova-Davis, PhD, an assistant professor in the Department of and Brain Repair at the University of South Florida.

Sanfilippo syndrome type B is caused by a deficiency in the Naglu gene, the gene responsible for producing an enzyme needed to degrade heparan sulfate. Naglu-deficient mice show progressive deterioration of movement, vision and hearing. in various parts of the brain – including the olfactory bulb, cortex, thalamus, amygdala, and other areas – are affected by the disease. Consequently, patients with MPS III B experience a variety of pathological brain changes.

"Among our findings was that endothelial cells and other cells comprising the blood-brain barrier are damaged, resulting in vascular leakage," said Dr. Garbuzova-Davis. "This compromise may lead to destruction of the fragile central nervous system equilibrium."

Dr. Garbuzova-Davis and her co-researchers also reported that the "insult to blood-brain barrier integrity" likely comes from accumulated storage products within the endothelial cells, which are primary cellular components of the BBB. The authors noted that it is possible that blood-brain barrier dysfunction occurred before, or concurrent with, the appearance of neuropathological changes in MPS III B.

"Interestingly, more capillary leakage was seen in some brain structures, such as the hippocampus, in early symptomatic mice than in late symptomatic mice," Dr. Garbuzova-Davis said. "We speculate that the regions of the brain differ in metabolic functional activity, especially in growing animals, and higher activity may require more substantial exchanges of nutrients and metabolic activity. If the blood-brain barrier is already weakened in these areas, more vascular leakage may occur."

The authors report that capillary endothelial cell dysfunction may accelerate neuropathological changes in MPS III B by potentially allowing harmful blood-borne soluble substances, including neurotoxins, to enter the central nervous system.

"Alternatively, damaged endothelial cells may alter specific mechanisms for transport of various solutes across the blood-brain barrier," said Paul Sanberg, PhD, DSc, executive director of USF Center of Excellence for Aging and and co-author of the paper. "In this scenario, neural cells might suffer the dual effects of reduced nutrition and increased metabolite levels, impairing central nervous system function."

The researchers concluded that determining the evolution of blood-brain barrier dysfunction in MPS III B is important for both understanding how the disease progresses and for developing therapies. One possibility for blood-brain barrier repair is replacement of affected endothelial cells with endothelial progenitor cells from bone marrow or umbilical cord blood. Because a microaneurysm was noted in the of a mouse modeling MPS III B, the authors also suggest that special attention be given to the possibility of cerebral hemorrhage in MPS III B patients caused by weakened integrity.

More information: Garbuzova-Davis S, Louis MK, Haller EM, Derasari HM, Rawls AE, et al. (2011) Blood-Brain Barrier Impairment in an Animal Model of MPS III B. PLoS ONE 6(3): e16601. doi:10.1371/journal.pone.0016601

Related Stories

Recommended for you

Fabric imbued with optical fibers helps fight skin diseases

February 23, 2018
A team of researchers with Texinov Medical Textiles in France has announced that their PHOS-ISTOS system, called the Fluxmedicare, is on track to be made commercially available later this year. The system consists of a piece ...

DNA gets away: Scientists catch the rogue molecule that can trigger autoimmunity

February 22, 2018
A research team has discovered the process - and filmed the actual moment - that can change the body's response to a dying cell. Importantly, what they call the 'Great Escape' moment may one day prove to be the crucial trigger ...

Low-calorie diet enhances intestinal regeneration after injury

February 22, 2018
Dramatic calorie restriction, diets reduced by 40 percent of a normal calorie total, have long been known to extend health span, the duration of disease-free aging, in animal studies, and even to extend life span in most ...

Artificial intelligence quickly and accurately diagnoses eye diseases and pneumonia

February 22, 2018
Using artificial intelligence and machine learning techniques, researchers at Shiley Eye Institute at UC San Diego Health and University of California San Diego School of Medicine, with colleagues in China, Germany and Texas, ...

Gut microbes protect against sepsis—mouse study

February 22, 2018
Sepsis occurs when the body's response to the spread of bacteria or toxins to the bloodstream damages tissues and organs. The fight against sepsis could get a helping hand from a surprising source: gut bacteria. Researchers ...

Breakthrough could lead to better drugs to tackle diabetes and obesity

February 22, 2018
Breakthrough research at Monash University has shown how different areas of major diabetes and obesity drug targets can be 'activated', guiding future drug development and better treatment of diseases.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.