Abstracts

Rationale: Increased T2-weighted signal is a common finding in the hippocampus of patients with drug-resistant temporal lobe epilepsy (TLE). The histopathological examination often reveals hippocampal sclerosis, characterized by neuronal loss and astrogliosis. Human and experimental studies have shown changes in the expression and location of aquaporin 4 (AQP4) in TLE, and suggest that these changes can affect water homeostasis. Since water content in brain tissue can also impact T2 signal, our aim was to evaluate if hippocampal AQP4 expression is related with the changes in T2 relaxometry of TLE patientsMethods: Patients with TLE (n = 26) were scanned prior to surgical resection of the hippocampus in a 3 Tesla MRI scanner. For T2 relaxometry, spin echo images with multiples echoes (TE = 20, 40, 60, 80 and 100 ms; TR = 3 s) were acquired and post-processed. Age-matched controls were obtained from voluntaries (radiological control, RC, n = 12) for the MRI measurements, and from autopsy tissues (histological control, HC, n = 6) for the immunohistochemistry analysis. Immunohistochemistry for AQP4 and GFAP was performed in formalin fixed, paraffin embedded tissues and analyzed under light microscopy. Quantification of Immunohistochemistry was evaluated using Image J software and results were expresssed as immunopositive area. Results were considered significant at p < 0.05Results: Immunohistochemistry for AQP4 revealed a stronger staining though all neuropile in TLE patients when compared to HC. In contrast with HC, TLE patients have also decreased perivascular AQP4 expression. Increased AQP4 immunopositive area was observed in CA2, prosubiculum and subiculum (p 0.045) of TLE patients when compared to HC. Increased immunopositive GFAP area was observed in the hippocampus of TLE patients, when compared to HC, in all hippocampal subfields (p 0.009). TLE patients presented increased hippocampal T2 relaxation time, when compared to RC (p = 0.005). No correlation was observed between AQP4 expression and T2 relaxometry.The hippocampal relaxation time correlated with GFAP area fraction in the subiculum (r = 0.541; p = 0.0296)Conclusions: Our findings indicate that the gliosis in the sclerotic hippocampus is probably the main substrate responsible for the increased T2 relaxometry, and that changes in water content due to decreased AQP4 function may occur, but it probably is not sufficient to further increase T2 signal