title: Individual hippocampal subfield assessment indicates that matrix macromolecules and gliosis are key elements for the increased T2 relaxation time seen in temporal lobe epilepsy.
abstract: Increased T2 relaxation time is often seen in temporal lobe epilepsy (TLE) with hippocampal sclerosis. Water content directly affects the effective T2 in a voxel. Our aim was to evaluate the relation between T2 values and two molecules associated with brain water homeostasis aquaporin 4 (AQP4) and chondroitin sulfate proteoglycan (CSPG), as well as cellular populations in the hippocampal region of patients with TLE.
  
  
  
  Hippocampal T2 imaging and diffusion tensor imaging (DTI) were obtained from 42 drug-resistant patients with TLE and 20 healthy volunteers (radiologic controls, RCs). A similar protocol (ex vivo) was applied to hippocampal sections from the same TLE cases and 14 autopsy control hippocampi (histologic and radiologic controls, HRCs), and each hippocampal subfield was evaluated. Hippocampal sections from TLE cases and HRC controls were submitted to immunohistochemistry for neurons (neuron nuclei [NeuN]), reactive astrocytes (glial fibrillary acidic protein [GFAP]), activated microglia (human leukocyte antigen-D-related [HLA-DR]), polarized AQP4, and CSPG.
  
  
  
  Patients with TLE had higher in vivo and ex vivo hippocampal T2 relaxation time. Hippocampi from epilepsy cases had lower neuron density, higher gliosis, decreased AQP4 polarization, and increased CSPG immunoreactive area. In vivo relaxation correlated with astrogliosis in the subiculum and extracellular CSPG in the hilus. Ex vivo T2 relaxation time correlated with astrogliosis in the hilus, CA4, and subiculum, and with microgliosis in CA1. The difference between in vivo and ex vivo relaxation ratio correlated with mean diffusivity and with the immunopositive area for CSPG in the hilus.
  
  
  
  Our data indicate that astrogliosis, microgliosis, and CSPG expression correlate with the increased T2 relaxation time seen in the hippocampi of patients with TLE.
authors.affiliation: Department of Neurosciences and Behavioral Sciences, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Jose Eduardo
authors.identifier: 0000-0001-7461-1902
authors.initials: JE
authors.lastname: Peixoto-Santos
authors.affiliation: Department of Neurosciences and Behavioral Sciences, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Ludmyla
authors.identifier: 0000-0003-4387-5977
authors.initials: L
authors.lastname: Kandratavicius
authors.affiliation: Department of Neurosciences and Behavioral Sciences, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Tonicarlo Rodrigues
authors.identifier: 0000-0001-7756-8882
authors.initials: TR
authors.lastname: Velasco
authors.affiliation: Department of Surgery and Anatomy, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Joao Alberto
authors.initials: JA
authors.lastname: Assirati
authors.affiliation: Department of Surgery and Anatomy, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Carlos Gilberto
authors.initials: CG
authors.lastname: Carlotti
authors.affiliation: Department of Neurosciences and Behavioral Sciences, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Renata Caldo
authors.initials: RC
authors.lastname: Scandiuzzi
authors.affiliation: Department of Physics and Mathematics, Faculty of Philosophy, Science and Languages of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Carlos Ernesto Garrido
authors.initials: CE
authors.lastname: Salmon
authors.affiliation: Department of Internal Medicine, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Antonio Carlos Dos
authors.initials: AC
authors.lastname: Santos
authors.affiliation: Department of Neurosciences and Behavioral Sciences, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Joao Pereira
authors.identifier: 0000-0003-0558-3519
authors.initials: JP
authors.lastname: Leite
mesh_terms: D000328:Adult; D051401:Aquaporin 4 / Q000378:metabolism*; D016022:Case-Control Studies; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D056324:Diffusion Tensor Imaging; D004833:Epilepsy, Temporal Lobe / Q000150:complications / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology* / Q000473:pathology; D006680:HLA Antigens / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012598:Sclerosis / Q000000981:diagnostic imaging; D013223:Statistics as Topic; D013997:Time Factors
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D011508:Chondroitin Sulfate Proteoglycans; D005904:Glial Fibrillary Acidic Protein; D006680:HLA Antigens; D010751:Phosphopyruvate Hydratase
keywords: Chondroitin sulfate; Gliosis; Magnetic resonance imaging; Subfield evaluation; T2-weighted imaging; Temporal lobe epilepsy