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Temporal lobe epilepsy patients with severe hippocampal neuron loss but normal hippocampal volume: Extracellular matrix molecules are important for the maintenance of hippocampal volume
Author(s) -
PeixotoSantos Jose Eduardo,
Velasco Tonicarlo Rodrigues,
GalvisAlonso Orfa Yineth,
Araujo David,
Kandratavicius Ludmyla,
Assirati Joao Alberto,
Carlotti Carlos Gilberto,
Scandiuzzi Renata Caldo,
dos Santos Antonio Carlos,
Leite Joao Pereira
Publication year - 2015
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13082
Subject(s) - hippocampal formation , hippocampal sclerosis , astrogliosis , hippocampus , glial fibrillary acidic protein , temporal lobe , neuron , epilepsy , population , pathology , neuroscience , chemistry , medicine , endocrinology , immunohistochemistry , psychology , central nervous system , environmental health
Summary 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 CA 1 and prosubiculum, and with immunopositive areas for CS ‐56 in CA 1, and negatively with immunopositive area for GFAP in CA 1. Multiple linear regression analysis indicated that both neuron density and CS ‐56 immunopositive area in CA 1 were statistically significant predictors of hippocampal volume. Significance Our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA 1 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.