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)

Peixoto-Santos, Jose Eduardo ^[1] ; Velasco, Tonicarlo Rodrigues ^[1] ; Galvis-Alonso, Orfa Yineth ^[2] ; Araujo, David ^[3] ; Kandratavicius, Ludmyla ^[1] ; Assirati, Joao Alberto ^[4] ; Carlotti, Carlos Gilberto ^[4] ; Scandiuzzi, Renata Caldo ^[1] ; dos Santos, Antonio Carlos ^[5] ; Leite, Joao Pereira ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Neurosci & Behav, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Sao Jose do Rio Preto Med Sch, Dept Mol Biol, Sao Jose Do Rio Preto, SP - Brazil

^[3] McGill Univ, Montreal Neurol Inst, Montreal, PQ - Canada

^[4] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Surg, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Internal Med, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Epilepsia; v. 56, n. 10, p. 1562-1570, OCT 2015.
• Web of Science Citations: 14

Abstract

ObjectiveHippocampal 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. MethodsPatients 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. ResultsBoth 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. SignificanceOur 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. (AU)

• FAPESP's process: 05/56447-7 - Research through images from high field magnetic resonance aimed at studies in humans
• Grantee: João Pereira Leite
• Support type: Inter-institutional Cooperation in Support of Brain Research (CINAPCE) - Thematic Grants
• FAPESP's process: 09/53447-7 - Synaptic and non synaptic mechanisms of refractory epilepsy and its implications in searching for new therapeutic strategies: translational approach
• Grantee: João Pereira Leite
• Support type: Research Projects - Thematic Grants