Abstracts

Rationale: The hippocampus of drug-resistant temporal lobe epilepsy patients (TLE) often presents atrophy, increased T2 relaxation, and reduced magnetization transfer ratio (MTR). For these patients, the histological correlates of the reduced MTR are unknown. Since MTR is dependent on the tissue’s macromolecules, our aim was to evaluate the correlations between cellular populations, extracellular matrix molecules and the MTR in TLE patients. Methods: Patients with TLE (n=27) were scanned before surgical resection of the hippocampus in a 3 Tesla MRI scanner. MTR images were calculated from 3DT1 sequences (TE=3.6 ms, TR=7.3 ms, magnetization pulse on resonance, voxel=1x1x3 mm). Age-matched controls were obtained from voluntaries (n=20) for the MR measurements, and from autopsy tissues (n=10) for the pathological measurements. Immunohistochemistries for NeuN (a marker of neurons), GFAP (a marker of reactive astrogliosis), and CS-56 (a marker for the extracellular matrix molecule chondroitin sulfate) were performed in formalin fixed, paraffin embedded tissues, and were evaluated as immunopositive area fraction. Results were considered significant at p Results: Compared to the respective controls, TLE patients had reduced hippocampal MTR (p<0.001), increased immunopositive GFAP area fraction (p<0.05), increased CS-56 immunopositive area (p<0.001), and reduced neuron density (p<0.001) in the hippocampal sections of TLE patients, compares to HC. MTR correlated with neuron density in CA3 (r=0.581, p=0.005) and with CS-56 immunopositive areas in CA3 (r=0.660, p=0.004), in CA1 (r=0.544, p=0.01), and in the subiculum (r=0.578, p=0.02). Conclusions: Our data indicate that extracellular matrix molecules are the most significant histological correlates of magnetization transfer ratio in the hippocampus of TLE patients. Funding: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), processes #2015/20840-9 and #2017/03739-8.