Abstracts

Rationale: Mesial temporal lobe epilepsy (MTLE) is often associated with poor seizure control. Hippocampal sclerosis is a common pathological finding in MTLE and is characterized by neuron loss and gliosis, which is particularly severe in the CA1 and prosubiculum subfields. Gliosis can increase extracellular matrix (ECM) production, affecting water homeostasis and extracellular space volume. Hyaluronan (HA) and chondroitin sulfate (CS), the main ECM molecules, are increased in MTLE patients. Aquaporin 4 (AQP4), a water channel found in astrocytes, is also altered on MTLE and can affect oedema generation and draining. Although studies have indicated association between CA1 neuron density and MRI hippocampal volume, the relative contribution of other tissue elements in the hippocampal volume has not been evaluated. Our aim was to evaluate the role of hippocampal neuron and glial populations, and molecules associated with water homeostasis in MTLE patients with different MRI hippocampal volumes. Methods: Patients with MTLE (n=69) were evaluated for MRI volumetry; and hippocampal histological sections from surgical biopsies and from autopsy patients without history and evidence of brain pathology (n=20) were processed for immunohistochemistry for NeuN, GFAP, HLA-DR, AQP4, CS-56 and histochemistry for HA. Neuronal population (neurons/mm3) was evaluated by cell count and all immunohistochemistry were evaluated by immunoreactive area (?m2). HA histochemistry was evaluated by gray level. Results: Hippocampal volumes in MTLE patients were of 2.314 0.063 cm3 (mean SEM), ranging from 1.338 to 3.704 cm3. Compared to control, MTLE showed lower neuronal density (Control = 41,853, MTLE = 4,484; Mann-Whitney, median, p<0.001), lower immunopositive areas for NeuN (Control = 474, MTLE = 55; p<0.001), perivascular AQP4 (Control = 179, MTLE = 85; p=0.001) and higher immunopositive areas of GFAP (Control = 52, MTLE = 2185; p<0.001), HLA-DR (Control = 11, MTLE = 62; p<0.001) and CS-56 (Control = 81, MTLE = 267; p=0.003). Positive correlations were found between hippocampal volume and neuronal density (r=0.405; p<0.001), hippocampal volume and immunoreactive areas for NeuN (r=0.451; p<0.001) and for CS-56 (r=0.295; p=0.024). Multiple linear regression models revealed, respectively, predictions of 37% (p<0.001) and 36% (p<0.001) of hippocampal volume for the combinations between immunoreactive areas of NeuN and CS-56 [Hippocampal Volume = 2.067 (0.00182 * CA1 NeuN area) (0.000334 * CA1 CS-56 area)] and of neuronal density and immunoreactive area for CS-56 [Hippocampal Volume = 2.050 (0.0309 * CA1 neuronal density) (0.000343 * CA1 CS-56 area)]. Conclusions: Hippocampal volume in MTLE is partially explained by neuronal population and extracellular matrix chondroitin sulfate quantity.