Resumo

Purpose: Markers of kinin systems, which are associated with inflammatory processes are overexpressed in the hippocampus of patients with temporal lobe epilepsy, associated to mesial sclerosis (TLE). Thus, the aim of this work was to examine the distribution of the enzyme, kallikrein 1 (hK1) and the expression of mRNA gene (KLK1), which is responsible for kinin release in tissue, after the cleavage of the low molecular weight kininogen in the sclerotic hippocampus. These data were compared with control tissues, obtained after autopsy of subjects with no brain pathology. Methods: The expression of KLK1 mRNA was analyzed using Real Time PCR and the protein hK1 distribution was studied using immuno-histochemistry, associated with double staining (confocal microscopy) with different cell markers. Kinin B1 and B2 receptors were co-localized with NeuN and the enzyme hK1 was co-localized with GFAP in the hippocampus of patients and controls. Results: The results showed increased expression of hK1in astrocytes co-localized with GFAP and increased expression of mRNA KLK1 in the hippocampus of these patients. In addition, the kinin B1 and B2 receptors were up-regulated in neurons of TLE patients, showing the participating of different types of cells in kinin system signalization. Conclusion: The data suggest a cross-talk between neuronal and glial cells in kallikrein-kinin system in human TLE, which could be summarized as: long-lasting seizures can induce increase in mRNA KLK1 expression by astrocytes with consequent cleavage of human kininnogen, releasing kinins. These short-living peptides acting on kinin B1 receptors could induce excitotoxicity and acting on kinin B2 receptors promote neuroprotection.