ABSTRACT
OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor) on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus. .
Subject(s)
Animals , Male , Cyclooxygenase Inhibitors/pharmacology , Hippocampus/drug effects , Indomethacin/pharmacology , Monokines/drug effects , Receptors, Bradykinin/drug effects , Status Epilepticus/drug therapy , Disease Models, Animal , Down-Regulation/drug effects , Interleukin-1beta/analysis , Interleukin-1beta/drug effects , Monokines/analysis , Pilocarpine , Rats, Wistar , Receptor, Bradykinin B1/analysis , Receptor, Bradykinin B1/drug effects , /analysis , /drug effects , Receptors, Bradykinin/analysis , Status Epilepticus/chemically induced , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/drug effectsABSTRACT
The increase in sensitivity of guinea pig preparations to bradykinin (BK) due to stretching occurring with time after mounting was studied by determining the time course of changes in the cell membrane potential, measured with intracellular microelectrodes. A sustained hyperpolarizing effect of BK, which was observed in recently mounted preparations, became transient after 120 min, when it was followed by depolarization, which was much more evident after 4 h of stretching. As a consequence, a parallel increase in the contractile response to BK was also observed. The hyperpolarizing effect was due to the opening of Ca²+-dependent K+ channels sensitive to apamin, since BK dose-response curves done within 1 h of mouting were shifted to the left, becoming similar to dose-response curves obtained 4 h after mounting of the guinea pig ileum preparation. These results were specific for BK, since the potentiating effect of apaming was not observed for acetylcholine. Our results show that the activation of B2 receptors by BK in the isolated guinea pig ileum induce a dual effect - hyperpolarization and depolarization - and that the increase in the contractile response consequent to stretching is probably due to the inactivation of apaminsensitive Ca²+-dependent K+ channels