Нейровоспалительные процессы влияют на структурные изменения в миндалине крыс в литий-пилокарпиновой модели эпилепсии

Abstract

Temporal lobe epilepsy is a severe neurological disease known to be difficult to treat. It is associated with the development of neuroinflammation, astrogliosis and neuron death. Amygdala is known to play an important role in epileptogenesis. However, the exact mechanisms remain poorly studied. In this study, the structural and biochemical changes in the basolateral region of the rat amygdala were analyzed using the lithium-pilocarpine model of temporal lobe epilepsy. Status epilepticus was induced in 7-8-week-old male Wistar rats. Two subgroups of rats were studied: (1) with prolonged (>3 h) and short (<1.5 h) seizures. This division into two groups was motivated by the dependence of the development of spontaneous seizures in the chronic phase of the model on the severity and duration of seizures during the status epilepticus. The investigation was performed in the latent and chronic period of the model (3 and 7 days and 2 months after the pilocarpine administration) using light and electron microscopy, as well as immunohistochemical analysis of the distribution of the neuronal (Fox3) and glial (GFAP, Iba1) markers in the amygdala. Analysis of the Il1b and Tnfa gene expression producing pro-inflammatory cytokines was performed by the method of rtPCR on day 7 after status epilepticus. During the first week after pilocarpine treatment, a decrease in the number of neurons and a significant increase in the number of astroglial and microglial cells were shown in the basolateral amygdala of rats with prolonged seizures. In rats with short-term seizures, the gliosis was absent, and the death of neurons was less pronounced. The study of the ultrastructure revealed the clusters of lysosomes and other neurodegenerative changes in the neurons of the amygdala of rats with prolonged convulsions. These structural abnormalities were accompanied by increased expression of the genes Il1b and Tnfa, which indicates the development of neuroinflammatory processes. Changes detected in the amygdala cells in rats with prolonged seizures may be involved in the mechanisms of epileptogenesis and associated behavioral disorders.