Avaliação da modulação de transcrição promovida por células-tronco mesenquimais da medula óssea sobre co-transportadores cátion-cloreto (CCC) na epilepsia experimental

Abstract

Temporal Lobe Epilepsy is a disease of the Central Nervous System, characterized by rhythmic and synchronized firing of neuronal populations that lead to spontaneous and recurrent seizures in individuals affected by this pathology. This type of epilepsy has clinical relevance due to its high incidence rate, as well as its refractoriness rate, with 30% of individuals affected by this disturb not responding to drug treatment. Given this scenario, it is necessary to search for alternatives that promote benefits to individuals with this disease. Currently, a major focus is on cell therapy with stem cells, due to its benefits and less invasive character in its administration. Within these cells, mesenchymal stem cells appear. These cells have multipotent capacity and can differentiate into different tissues, in addition to the ability to modulate diseased niches. Thus, the present work sought to evidence the effect that mesenchymal stem cells promote in the context of temporal lobe epilepsy induced by the pilocarpine model in rats under the cation-chloride co-transporters NKCC1 and KCC2. For this purpose, mesenchymal stem cells were extracted from the bone marrow of Wistar rats, cultured and transplanted into healthy Wistar rats and animals induced to status epilepticus by pilocarpine.. As a result, we were able to observe that the mesenchymal stem cells were able to change the amount of transcript in the brain of the animals. When the brain is stratified in areas, we can observe the increase in NKCC1 directly to the tonsils and hippocampi, structures that participate in the limbic lobe and are affected in epilepsy. We can also observe a decrease in the expression of KCC2 in the brain of the animals at 1 day post-transplant and an increase at 7 days post-transplant. Also, KCC2 expression showed a kind of pattern at 1 day posttransplant. Thus, we conclude that mesenchymal stem cells have a modulatory function on the levels of gene expression of cation-chloride co-transporters NKCC1 and KCC2 during acute phase of epilepsy.