title: Temporal lobe epilepsy patients with severe hippocampal neuron loss but normal hippocampal volume: Extracellular matrix molecules are important for the maintenance of hippocampal volume.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurosciences and Behavior, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Jose Eduardo
authors.initials: JE
authors.lastname: Peixoto-Santos
authors.affiliation: Department of Neurosciences and Behavior, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Tonicarlo Rodrigues
authors.initials: TR
authors.lastname: Velasco
authors.affiliation: Department of Molecular Biology, São José do Rio Preto Medical School, Sao Jose do Rio Preto, Sao Paulo, Brazil.
authors.forename: Orfa Yineth
authors.initials: OY
authors.lastname: Galvis-Alonso
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Araujo
authors.affiliation: Department of Neurosciences and Behavior, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Ludmyla
authors.initials: L
authors.lastname: Kandratavicius
authors.affiliation: Department of Surgery, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirao Preto, Brazil.
authors.forename: Joao Alberto
authors.initials: JA
authors.lastname: Assirati
authors.affiliation: Department of Surgery, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirao Preto, Brazil.
authors.forename: Carlos Gilberto
authors.initials: CG
authors.lastname: Carlotti
authors.affiliation: Department of Neurosciences and Behavior, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Renata Caldo
authors.initials: RC
authors.lastname: Scandiuzzi
authors.affiliation: Department of Internal Medicine, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirao Preto, Brazil.
authors.forename: Antonio Carlos dos
authors.initials: AC
authors.lastname: Santos
authors.affiliation: Department of Neurosciences and Behavior, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Joao Pereira
authors.initials: JP
authors.lastname: Leite
mesh_terms: D016022:Case-Control Studies; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004833:Epilepsy, Temporal Lobe / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012044:Regression Analysis
chemical_list: D005904:Glial Fibrillary Acidic Protein; D002809:Chondroitin Sulfates; D010751:Phosphopyruvate Hydratase
keywords: Epilepsy; Extracellular matrix; Gliosis; Hippocampal volumetry; Magnetic resonance imaging; Neuronal density