Dados do Trabalho

Título

EVALUATION OF THE THERAPEUTIC EFFECT OF MESENCHYMAL STEM CELLS DERIVED FROM BONE MARROW IN THE ISOFORM OF T-TYPE CALCIUM CHANNELS IN ACUTE EPILEPSY

Introdução

Temporal lobe epilepsy (TLE) is the most prevalent form of refractory epilepsy, affecting about 20% of all cases, and is characterized by the disordered, synchronous, and rhythmic firing of the neuronal population of the Central Nervous System. These events can cause deregulation of the voltage-dependent calcium channels, known as T-type calcium channels, increasing neuronal excitability in TLE. The CACNA1H is one isoform of the T-type calcium channels. Mesenchymal Stem Cells (MSCs) can modulate neurotransmitters liberation, reduce neuronal death, and increase neurogenesis.

Objetivo

Therefore, this study analyzed the MSCs effects on gene expression of the CACNA1H in the brain of pilocarpine-induced TLE animal models.

Método

The MSCs were obtained from the bone marrow of Wistar rats, cultured, characterized, and transplanted intranasal (IN) and intravenously (IV). The animals were separated into two groups: control and pilocarpine-induced status epilepticus, then they were euthanized 1 and 7-days post-transplant for gene expression analysis, of the amygdala, hippocampus, prefrontal cortex, and the entorhinal cortex, by real-time polymerase chain reaction.

Resultados

The results show that in the whole brain after 1 and 7-days post-transplant there was no difference in the CACNA1H gene expression between the MSC-treated pilocarpine groups and the control and untreated pilocarpine groups, in the two routes of administration. There was a difference in temporal analysis between the treated pilocarpine group, in the IN and IV, this also occurred in the prefrontal cortex. In the amygdala, 1-day after-treatment there was no significant difference between groups, both IN and IV. Only in the 7-days, it had a difference between the groups treated with MSCs and untreated groups, both routes. In the hippocampus and the entorhinal cortex 1 and 7-days post-treatment, there was difference between the groups treated with MSCs and untreated groups, both routes of administration.

Conclusão

The animals in the pilocarpine group showed reduced relative expression, in most cases negative in relation to the other groups, both IN and IV and in the temporal analysis, leading to believe that these channels have already had been recruited in the initial insult, demonstrating that this gene is related to the epileptogenic event. Thus, MSCs were able to modulate the expression of the CACNA1H gene in the brain, suggesting its importance as a target for future studies on epilepsy therapies involving cells.

Palavras-chave

T-type Calcium Channels; Epilepsy; Cell Therapy.