Navigation Links
University of South Florida researchers find blood-brain barrier damaged by disease
Date:3/8/2011

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 mouse model of MPS III B, has been published online in the journal PLoS One. Before this study, little was known about the integrity of the blood-brain barrier in this disease. (www.plosone.com)

"These new findings about blood-brain barrier structural and functional impairment in MPS III B mice, even at early disease stage, may have implications for disease pathogenesis 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 Neurosurgery 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. Neurons 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 Brain Repair 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 brain 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.


'/>"/>

Contact: Randolph Fillmore
rfillmor@health.usf.edu
813-974-0868
University of South Florida (USF Health)
Source:Eurekalert

Related medicine news :

1. University of Virginia Health System Medical Laboratories Selects Sunquest's Specimen Collection Solution
2. Akron Institute of Herzing University Launches Its First Bachelors Degree Programs to Prepare Students for Even Greater Success in Business, Health Care and IT
3. Most pandemic plans in Ontario hospitals have not been tested: Queens University study
4. San Diego State University and BIOCOM Institute Receive $4.95 Million Grant: The BRIDGE Project, Linking Education to Employment in San Diegos Life Sciences Industry
5. Smithsonian Institution, Arizona State University announce education and research partnership
6. Untreated poor vision in elderly linked to dementia, University of Michigan study shows
7. Giarmarco, Mullins & Horton, P.C. President Joseph F. Page to Speak at University of Michigan
8. Arizona State Universitys Decision Theater offers balance to an off-kilter world
9. Forest City Announces Joint Venture with Health Care REIT for University Park Life Science Properties
10. Herzing University Online Launches Master and Bachelor of Science Degrees in Nursing
11. Nurtur Acquires ActivHealth and Wellness by Choice; Gains Exclusive Partnership with Duke University Center for Living
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/24/2017)... ... 24, 2017 , ... The California State University Institute for Palliative Care ... or interested in palliative care education and research. The Symposium, “Innovate. Investigate. Educate: ... San Diego on Sept. 28 and 29, 2017, on the campus of California State ...
(Date:2/24/2017)... ... ... Indiana Fiber Network (IFN) President and CEO Kelly C. Dyer recently announced that ... Chairman of the Management Committee when IFN was originally formed in 2002 where he ... and development of the business plan. He became the first paid employee of ...
(Date:2/24/2017)... ... February 24, 2017 , ... Congratulations to Head ... division on February 12th. Ms. Esparza qualified into this prestigious status after ... held in Las Vegas, Nevada. Frida is one of approximately 25 gymnasts in ...
(Date:2/23/2017)... ... February 23, 2017 , ... ... jointly issued a letter to withdraw previous guidance issued by the ... identity. The guidance issued in May 2016 by the Obama Administration came in ...
(Date:2/23/2017)... ... February 23, 2017 , ... Rare Disease Report®, ... be participating in Rare Disease Day events, hosted by the Rare Disease Legislative ... Report, a website, weekly e-newsletter and quarterly publication, will be conducting interviews with ...
Breaking Medicine News(10 mins):
(Date:2/23/2017)...  MiMedx Group, Inc. (NASDAQ: MDXG), the leading regenerative ... to develop and market advanced products and therapies for ... and Dental sectors of healthcare, today announced its record ... December 31, 2016. Full Year 2016 Highlights ... increase over full year 2015 revenue ...
(Date:2/23/2017)... On Wednesday, February 22, 2017, US markets saw ... sectors finished the trading sessions in green, four closed in ... indices were also mixed at the close of yesterday,s session. ... by 0.09%; the Dow Jones Industrial Average edged 0.16% higher, ... 2,362.82, down 0.11%. This Thursday morning, Stock-Callers.com looks at the ...
(Date:2/23/2017)... 2017 Tillotts Pharma is strengthening ... Berlin office was opened in January 2017 ... portfolio includes Entocort ® for the treatment of ... ulcerative colitis, and VistaPrep ® for bowel preparation ... pharmaceutical company focused on the treatment of gastrointestinal (GI) ...
Breaking Medicine Technology: