A pilocarpine-induced animal model for pathogenesis and treatment of Temporal Lobe Epilepsy

다국어 초록 (Multilingual Abstract)

Epileptic seizure disorders are characterized by unpredictable abnormal electrical discharge, loss of consciousness, and convulsions. 60% of adult patients are Temporal lobe epilepsy(TLE), and 60% of them have hippocampal sclerosis. TLE patients have a poor prognosis and, in particular, when hippocampal sclerosis is accompanied, the cure rate decreases to less than 20%. The pilocarpine rodents model exhibiting hippocampal sclerosis is commonly used in TLE research and has been well known. However, it is difficult to establish a modeling protocol due to the very high mortality rate and the low efficiency with which spontaneous recurrent seizures(SRS) is observed. In this study, we constructed a suitable rodent model for epilepsy studies by our well established protocol using pilocarpine. We used C57BL/6J mice to inject various concentrations of pilocarpine, and established a pilocarpine-induced TLE model by optimizing the effective concentrations for seizure induction. We also investigated the mechanisms of epileptogenesis and characterized the neuropathology. Importantly, hippocampal neurons were damaged in pilocarpine injected mice, and gliosis was confirmed with an increase in the number of astrocytes. Furthermore, we identified the increased mRNA levels at various receptors, including the glutamic acid receptor in the hippocampus. These results show that our protocol to construct a rodent TLE model is well established, which suggests that the TLE model animals could be used to evaluate the effects of the various therapeutic drugs such as the small molecules or the genes or the stem cells. This work was supported by the Ministry of Science and ICT (2019M3E5D5065399) of the government of Korea.