heparitin-sulfate and Sclerosis

Extracellular matrix proteoglycans (PGs) and glycosaminoglycans (GAGs) play a crucial role in cell differentiation and synaptogenesis by modulating neurite outgrowth. The chondroitin sulfate (CS)-rich PG, the receptor protein tyrosine phosphatase zeta/beta (RPTP zeta/beta), has been related to neural morphogenesis and axon guidance. Hippocampal sclerosis is the most frequent pathologic finding in patients with intractable mesial temporal lobe epilepsy (MTLE), which is associated with neuron loss, reactive gliosis, and mossy fiber sprouting. In the present study, we investigated the concentration of CS, heparan sulfate (HS) and hyaluronic acid (HA) in the hippocampus and temporal neocortex as well as RPTP zeta/beta expression in the hippocampus of patients with MTLE. Compared to autopsy control tissue, epileptic hippocampi showed a significantly increased concentration of CS (224%; p=0.0109) and HA (146%; p=0.039). HS was instead similar to control values. No differences were found in the concentration of CS, HS, or HA in the temporal neocortex of epileptic patients when compared to control values. In contrast, RPTP zeta/beta immunoreactivity was induced in astrocytes of the inner molecular layer of the dentate gyrus of the sclerotic hippocampus. Because matrix compounds have been associated with tissue injury and repair, the present findings suggest that changes in PGs and GAGs might be related to damage-induced gliosis and neuronal reorganization in the hippocampus of MTLE patients.

Topics: Adult; Cerebral Cortex; Chondroitin Sulfates; Epilepsy, Temporal Lobe; Glycosaminoglycans; Heparitin Sulfate; Hippocampus; Humans; Hyaluronic Acid; Nerve Tissue Proteins; Protein Tyrosine Phosphatases; Proteoglycans; Receptor-Like Protein Tyrosine Phosphatases, Class 5; Sclerosis

We have previously reported the production of monoclonal antibodies (MAb) recognizing the core protein of a basement membrane-specific chondroitin sulfate proteoglycan (BM-CSPG). Using immunohistochemical techniques, we have shown that BM-CSPG is present in almost every basement membrane, one exception being the normal glomerular capillary basement membrane (GBM), where it is absent. In the present study of mature kidneys we examined the distribution of BM-CSPG in streptozocin-induced diabetes mellitus in rats. We found BM-CSPG atypically associated with the GBM of diabetic animals as early as 1 month after induction of diabetes mellitus. Immunoelectron microscopy (IEM) of affected capillary loops showed BM-CSPG present in the subendothelial matrix in areas of GBM thickening and absent in areas where the GBM appears to be of normal thickness. Moreover, the association of BM-CSPG with regions of the pericapillary GBM affects the morphology of the capillary endothelial cells within these areas, directly displacing the cell body from the GBM proper and causing loss of fenestrae. These new data on BM-CSPG distribution reflect abnormal glomerular extracellular matrix protein biosynthesis/turnover in diabetes and suggest that BM-CSPG in the GBM might in turn affect normal capillary structure and/or function.

Topics: Animals; Basement Membrane; Chondroitin Sulfate Proteoglycans; Diabetes Mellitus, Experimental; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Immunohistochemistry; Kidney Glomerulus; Laminin; Male; Microscopy, Immunoelectron; Proteoglycans; Rats; Rats, Sprague-Dawley; Sclerosis; Streptozocin; Tissue Distribution

Distribution of the eight components of extracellular matrix in small villi of human placenta was studied with indirect immunofluorescence. Normal full-term pregnancy was found to present rough fibers and type I collagen conglomerates accumulated in the stromal center, while type III and V collagens occurred all over the villous surface. Stromal localization of type IV collagen was recorded as well as its presence in basal membranes of the epithelium and vessels. Fibronectin showed diffuse distribution concentrating along the vessels. Laminin, entactin and in lesser degree heparan sulphate proteoglycan were registered in epithelial and vascular basal membranes. Isolated sclerosis of the villi in pathological pregnancy involved stromal accumulation of type I, III collagens, small fragments of collagens type IV, V and fibronectin. Multiple sclerosis of adherent villi demonstrated hyalin-like conglomerates of various collagens and fibronectin filling up the stroma. Laminin, heparan sulphate proteoglycan and entactin were not observed at these sites.

Topics: Basement Membrane; Chorionic Villi; Collagen; Extracellular Matrix; Female; Fibronectins; Fluorescent Antibody Technique; Glycoproteins; Heparitin Sulfate; Humans; Laminin; Membrane Glycoproteins; Pregnancy; Sclerosis