Neuroinfl ammatory Processes Affect Structural Changes in the Amygdala of Rats in a Lithium-Pilocarpine Model of Epilepsy

Temporal epilepsy is a severe neuromental disorder which is difficult to treat and whose pathogenesis is presumptively linked with the development of neuroinflammation, astrogliosis, and neuron death. The least studied of these processes occur in the amygdala, a part of the brain playing an important role in epileptogenesis. This study analyzes the structural and biochemical changes occurring in the basolateral part of the amygdala in a lithium-pilocarpine model of temporal epilepsy. Status epilepticus was induced in Wistar rats aged 7–8 weeks. Two subgroups were identified: one with severe, prolonged convulsions and one with mild short-lived convulsions. This separation was linked with the relationship between the probability of developing spontaneous recurrent convulsions in the chronic phase of the model on the one hand and the severity and duration of convulsions during the period of status epilepticus on the other. Histological studies were performed during the latent and chronic periods of the model (3 and 7 days and 2 months after administration of pilocarpine) using light and electron microscopy methods, as well as immunohistochemical analysis of the distribution of neuronal (Fox3) and glial (GFAP, Iba1) markers in cells. The expression of the genes for the proinflammatory cytokines interleukin-1β (Il1b) and tumor necrosis factor α (Tnfa) was analyzed by reverse transcription and the real-time polymerase chain reaction on day 7 after status epilepticus. During the first week after administration of pilocarpine into the basolateral amygdala, rats with prolonged convulsions showed decreases in the number of neurons and significant increases in the numbers of astrocytes and microglial cells. Rats with short-term convulsions showed no glial reaction and cell death was less extensive. Ultrastructural studies demonstrated accumulations of lysosomes and other neurodegenerative changes in amygdalar neurons of rats with prolonged convulsions. These abnormalities were accompanied by increased expression of the Il1b and Tnfa genes, pointing to the development of neuroinflammatory processes. Changes found in amygdalar cells in rats with severe long-lasting convulsions could be among the key mechanisms of epileptogenesis and associated comorbid behavioral abnormalities.

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Correspondence to D. S. Vasilev.

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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 105, No. 6, pp. 694–706, June, 2019.

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Vasilev, D.S., Tumanova, N.L., Kovalenko, A.A. et al. Neuroinfl ammatory Processes Affect Structural Changes in the Amygdala of Rats in a Lithium-Pilocarpine Model of Epilepsy. Neurosci Behav Physi (2020). https://doi.org/10.1007/s11055-020-00944-9

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Keywords

  • amygdala
  • lithium-pilocarpine model
  • temporal epilepsy
  • convulsions
  • neuroinfl ammation
  • glial reaction