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7. The University of South Florida, Dr. Paul R. Sanberg During the last few years, our research group at the University of South Florida has studied the potential of human umbilical cord blood (hUCB) stem cells to treat various neurodegenerative disorders (stroke, ALS, Parkinson’s disease), as well as brain and spinal cord injuries. Data suggest that these cells are able to repair a damaged or defective nervous system. In Sanfilippo Syndrome type B, a deficiency of the Naglu enzyme leads to accumulation of heparan sulfate, a major feature of this disease. We have previously shown that human umbilical cord blood cells reduced disease-related changes after intravenous (iv) injection into Naglu-deficient mice, probably due to delivery of the missing enzyme. Although administered cells were found widely distributed among different brain structures, the mechanism of cell migration to the brain is still unclear. One possibility is that cell migration to damaged areas of the brain occurs due to “signaling” substances in damaged tissues, substances that attract the transplanted cells. Another possible mechanism of transplant cell migration may be crossing of a damaged blood-brain barrier (BBB). However, no data exist about the BBB condition in Sanfilippo. The aim of this study was to determine whether the BBB is damaged in a mouse model of Sanfilippo type B at different stages of disease. Evans Blue (EB) dye was iv injected into Naglu mice to assess BBB integrity at early or late stage disease. Wild type mice (controls) were also injected at the same ages. After 30 minutes mice were euthanatized and the brains were examined for EB leakage. Also, immunohistochemical staining for albumin was performed in serial brain sections. Results showed EB and albumin vascular leakage in various brain structures of early and late symptomatic Naglu mice, males and females. More leakage was found in late symptomatic mice. Results suggest that the BBB is compromised in MPS III B mice even at early disease stage. These novel findings point to functional alterations of the BBB in a mouse model of MPS III B. One important aspect of these findings is that the BBB damage was determined in brain structures with known disease-related changes. However, structural dysfunction of BBB is uncertain. Future studies should include structural analysis of brain microvessels in Naglu mice by electron microscope. Determining structural and functional BBB damage in MPS III B is important not only for examining transplant cell migration, but it is also crucial to understanding additional mechanisms of disease and to developing pharmacological and cellular treatments. |
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