University of South Florida: Svitlana Garbuzova-Davis, PhD, DSc and Paul R. Sanberg PhD, DSc
The blood-brain barrier (BBB) maintains proper homeostasis in the central nervous system (CNS) by separating the brain tissue from the systemic blood circulation. Normal brain function depends on the exchanges of various substances across the BBB, exchanges that are regulated by specialized BBB structure in the microvessel wall. BBB breakdown is hypothesized to be a key component in CNS associated pathologies such as Multiple Sclerosis, Alzheimer’s disease, stroke, and ALS.
Recently, our research group at the University of South Florida has been studying BBB competence in an animal model of Sanfilippo Syndrome type B. We have shown that BBB structural and functional integrity are affected in microvessels of various brain structures in early and late symptomatic male and female mice. Endothelial cells and pericytes, cells composing the vascular wall, were highly vacuolated and contained GM3 gangliosides leading to cell damage. Also, a microaneurysm was identified adjacent to the ruptured endothelia, which led to vascular leakage. Importantly, BBB damage was determined in brain structures known to experience pathological changes, such as neuron vacuolization leading to neuron degeneration. More detailed study results can be found in our recently published article (PLoS ONE, 2011 March 7; 6(3): e16601). Our findings on BBB impairment in MPS III B were well received during two invited presentations: at the Sanfilippo Symposium in Orlando, Florida in the Arnold Palmer Hospital for Children sponsored by the Arnold Palmer Medical Center Foundation on April 8th and at the INTR-11 Conference in Clearwater, Florida on May 5th.
This new discovery of microvascular functional and structural damage in a mouse model of MPS III B even at early disease stage may have implications for disease pathogenesis in human Sanfilippo disease. The important role that BBB dysfunction could play in Sanfilippo pathology makes it necessary to investigate this possible damage in MPS III patients. Determining competence of BBB in patients with MPS III is important for understanding additional mechanisms of disease pathogenesis and for developing pharmacological treatments. Currently, we are evaluating BBB condition in human MPS III tissue. We are grateful to The Children’s Medical Research Foundation for supporting this study.
