Dados do Trabalho

Título

Intranasal transplantation of mesenchymal stem cells modulates gene expression of KCC2 cation-chloride cotransporter in experimental epilepsy

Introdução

Characterized by rhythmic and synchronized firing resulting from the excessive excitability of neuronal populations of the Central Nervous System, Temporal Lobe Epilepsy (TLE) is considered a disorder of great clinical relevance. About its incidence, it presents data in the magnitude of 65 million people affected around the world. An extremely important finding is the fact that about 30% of individuals who have this disorder do not respond effectively to available pharmacological treatments. Therefore, it is extremely important and relevant to seek and find therapeutic alternatives for individuals who are refractory to available drug treatments. In this context, cell therapy stands out and has shown promise for the investigation and promotion of new approaches. In this type of approach, we can highlight mesenchymal stem cells (MSC) for their regenerative properties, immunoregulatory capacity, ability to modulate diseased niches and their less invasive character. Therefore, a deeper understanding of the mechanisms by which this type of cell works is extremely important. One mechanism that can be explored is the modulation of symporters, in this case more specifically the KCC2 cation-chloride co-transporter. KCC2 is a symporter responsible for keeping the ionic levels of neuronal chloride in balance, thus preventing hyperexcitability and aiding in synaptic inhibition.

Objetivo

In this context, the present work aimed to analyze the gene expression related to the KCC2 cation-chloride co-transporter in TLE induced by the pilocarpine model in rats.

Método

Therefore, MSCs were extracted from the bone marrow of Wistar rats (humerus, femur and tibia), expanded in culture and aliquoted for transplantation intranasally at a density of 106 cells per animal.

Resultados

As a result, it was observed a decrease in the expression of KCC2 in the brain of the animals at 1-day post-transplant (down-regulation), and an increase at 7 days post-transplant (up-regulation). The loss of function of KCC2 decreases the release of chloride with a difficulty in inhibiting GABAergic inhibition, resulting in hyperexcitability of neuronal circuits. In this case, MSCs can promote rearrangement in gamma-aminobutyric acid-mediated inhibition, reducing hyperexcitability and hypersynchronicity.

Conclusão

In conclusion, we can observe that KCC2 has importance as a target for epilepsy, as well as MSCs have a modulating role in the expression levels of this gene in animals induced to the status epilepticus by pilocarpine.

Palavras-chave

temporal lobe epilepsy, intranasal therapy, stem cells