studies examining Sanfilippo Syndrome type B, namely disease mucopolysaccharidosis type III (MPS III B), showed that the barrier is responsible for protecting the brain against the penetration of harmful substances circulating in the blood, can be structurally and functionally damaged due to severe disease.Researchers from the University of South Florida found the defeat of certain brain structures involved in the development of the pathology of MPS III B, one of four species of Sanfilippo syndrome, which are inherited diseases of metabolism in the body.
The study, which was conducted on the basis of the model mice with MPS III B, was published online in the journal «PLoS One», published by the Open Science Library.Prior to this study, little was known about the integrity of the blood-brain barrier in this disease.
«The study of structural and functional damage to the blood brain barrier in mice with MPS III B is already at the initial stage of the disease can be applied when considering the pathogenes
At the heart of Sanfilippo syndrome type B is the lack of genes Naglu, responsible for the production of the enzyme needed to break down heparan sulfate.In mice with a lack of genes Naglu recorded the progressive deterioration of the functions of movement, vision and hearing.The neurons in different areas of the brain - including the olfactory bulb, cortex, thalamus, amygdala and other areas - are damaged as a result of the disease.As a consequence, patients with MPS III B have numerous abnormalities in the brain.
«Our results also showed that the damage to endothelial and other cells lining the blood-brain barrier, leading to increased permeability of the vessel wall and extravasation of fluid," - says Dr. Garbuzova Davis."Such a violation may lead to malfunction of the delicate balance of the central nervous system."
Garbuzova Dr. Davis and her colleagues also reported that "damage to the integrity of the blood-brain barrier" is likely to occur due to the abnormal accumulation of metabolites in endothelial cells, which are the major cellular components of blood brain barrier.The authors noted that the dysfunction of the blood-brain barrier may occur before or in parallel with the appearance of neuropathological changes in the MPS III B.
«Interestingly, increased capillary permeability in certain brain structures such as the hippocampus, observed mostly in mice with initial symptoms of the disease,compared to mice with advanced symptoms, "- says Dr. Garbuzova Davis."We think that the regions of the brain are different in functional activity of metabolism, particularly in growing organisms, and higher activity may require more substantial exchange of nutrients and metabolic activity.If the blood-brain barrier has weakened in these areas, there may be more increased vascular permeability. "
authors reported that dysfunction of the endothelial cells of capillaries can accelerate neuropathological changes in MPS III B, probably because the penetration of circulating soluble substances, including neurotoxins, in the central nervous system.
«Alternatively, damaged endothelial cells can alter some mechanism transporting various solutes across the blood-brain barrier," - said Paul Sanberg, Ph.D., Ph.D., director of the Center of Excellence in the field of aging and restore the functioning of the brain at the University of South Florida, andco-author."Under such conditions, the cells of the nervous system may suffer due to a double effect - a reduction of nutrient metabolism and increase - which has a negative effect on the central nervous system."
The researchers concluded that the study of dysfunction of the blood-brain barrier in MPS III B is important both for understanding the progression of the disease and to develop treatments.One of the possibilities to restore the blood brain barrier functions - replacing the damaged endothelial cells, endothelial progenitor cells from bone marrow or cord blood.Since the brains of mice with MPS III B was awarded microaneurysms, the authors also believe that special attention should be given to the possibility of cerebral hemorrhage in patients with MPS III B, which can be caused by weakened integrity.