chondroitin-sulfates and Epilepsy--Temporal-Lobe

Hippocampal sclerosis is a common finding in patients with temporal lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the reduction of hippocampal volume with the neuron loss seen on histologic evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major component of brain extracellular matrix, are also seen in hippocampal sclerosis. Our aim was to evaluate the association between hippocampal volume and chondroitin sulfate, as well as neuronal and astroglial populations in the hippocampus of patients with TLE.. Patients with drug-resistant TLE were subdivided, according to hippocampal volume measured by MRI, into two groups: hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE patients and age-matched controls were submitted to immunohistochemistry to evaluate neuronal population, astroglial population, and chondroitin sulfate expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary acidic protein (GFAP), and chondroitin sulfate (CS-56) antigens, respectively.. Both TLE groups were clinically similar. NV cases had higher hippocampal volume, both ipsilateral and contralateral, when compared to HA. Compared to controls, NV and HA patients had reduced neuron density, and increased GFAP and CS-56 immunopositive area. There was no statistical difference between NV and HA groups in neuron density or immunopositive areas for GFAP and CS-56. Hippocampal volume correlated positively with neuron density in CA1 and prosubiculum, and with immunopositive areas for CS-56 in CA1, and negatively with immunopositive area for GFAP in CA1. Multiple linear regression analysis indicated that both neuron density and CS-56 immunopositive area in CA1 were statistically significant predictors of hippocampal volume.. Our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA1 subfield are crucial for the hippocampal volume, and that chondroitin sulfate is important for the maintenance of a normal hippocampal volume in some cases with severe neuron loss.

Topics: Case-Control Studies; Chondroitin Sulfates; Epilepsy, Temporal Lobe; Female; Glial Fibrillary Acidic Protein; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Neuroglia; Neurons; Phosphopyruvate Hydratase; Regression Analysis

We have investigated changes in the extracellular matrix of the hippocampus associated with the early progression of epileptogenesis in a murine model of temporal lobe epilepsy using immunohistochemistry. In the first week following intrahippocampal injection of the glutamate agonist, domoate, there is a latent period at the end of which begins a sequential upregulation of extracellular matrix (ECM) molecules in the granule cell layer of the dentate gyrus, beginning with neurocan and tenascin-C. This expression precedes the characteristic dispersion of the granule cell layer which is evident at 14 days post-injection when the first recurrent seizures can be recorded. At this stage, an upregulation of the chondroitin sulfate proteoglycan, phosphacan, the DSD-1 chondroitin sulfate motif, and the HNK-1 oligosaccharide are also observed. The expression of these molecules is localized differentially in the epileptogenic dentate gyrus, especially in the sprouting molecular layer, where a strong upregulation of phosphacan, tenascin-C, and HNK-1 is observed but there is no expression of the proteoglycan, neurocan, nor of the DSD-1 chondroitin sulfate motif. Hence, it appears that granule cell layer dispersion is accompanied by a general increase in the ECM, while mossy fiber sprouting in the molecular layer is associated with a more restricted repertoire. In contrast to these changes, the expression of the ECM glycoproteins, laminin and fibronectin, both of which are frequently implicated in tissue remodelling events, showed no changes associated with either granule cell dispersion or mossy fiber sprouting, indicating that the epileptogenic plasticity of the hippocampus is accompanied by ECM interactions that are characteristic of the CNS.

Topics: Animals; Astrocytes; Axons; CD57 Antigens; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Cytoplasmic Granules; Dentate Gyrus; Electroencephalography; Epilepsy, Temporal Lobe; Extracellular Matrix Proteins; Fibronectins; Immunohistochemistry; Laminin; Male; Mice; Mossy Fibers, Hippocampal; Perfusion; Receptor-Like Protein Tyrosine Phosphatases, Class 5; Tenascin; Up-Regulation

This work studied the profile of glycosaminoglycans (GAGs) in the hippocampus, cortex, and cerebrospinal fluid of patients with temporal lobe epilepsy (TLE).. The GAGs were analyzed by agarose gel electrophoresis, enzymatic degradation, and enzyme-linked immunosorbent assay (ELISA).. The hippocampus of TLE patients showed increased levels of chondroitin sulfate and hyaluronic acid against normal levels of these GAGs in the neocortex and cerebrospinal fluid (CSF).. These results suggest that these matrix components could be involved in the pathophysiology of TLE.

Topics: Cerebral Cortex; Cerebrospinal Fluid; Chondroitin Sulfates; Epilepsy, Temporal Lobe; Extracellular Matrix; Glycosaminoglycans; Heparitin Sulfate; Hippocampus; Humans; Hyaluronic Acid

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