Estudo sobre o efeito do transplante de células mononucleares da medula óssea no modelo de epilepsia genética no camundongo EL

Abstract

Considering the high incidence of epilepsy (2-3% of world population) and the high rate of resistance to treatment with available antiepileptic drugs (20-30%) it is essential to be considered and made available new therapeutic options. In epilepsy, like other central nervous system disorders, there is loss of neuronal subpopulations, which represents an important consequence in the pathogenesis of the disease. Therapeutic strategies involving the transplantation of stem cells and gene therapy have been studied in experimental models of epilepsy. The genetic model of EL/Suz epilepsy mouse highlights among the experimental models. In this model, seizures originate close to the parietal lobe and spread to other brain regions such as the hippocampus. Some of the behavioral manifestations that they show are the manipulations of seizures associated with handling and vestibular stimulation, and this behavior is exacerbated by the increase with age of the animal. In order to exploit this potential, our study was to evaluate the effect of administration of bone marrow mononuclear cells in the treatment of genetics epilepsy by peripheral injection of these C57BL/6-EGFP cells in EL/Suz mice. The study was distributed in four groups: I) EL+Control (C), II) EL+Saline (S); III) EL+Bone Marrow Mononuclear Cells Inactivated (BMMCI), IV) EL+Bone Marrow Mononuclear Cells (BMMC). The animals were stimulated from birth with direct observation of behavioral manifestations from 30 days of life. Observation and stimulation of the animals were held once a week with the movement up and down the animal and commuting (goaround) in the four directions. To verify the presence of BMMC transplanted in the hippocampus and other brain structures, other agencies use the technique of polymerase chain reaction (PCR). The observation of the pro-and post-transplant groups was used as a parameter to infer that the transplanted mononuclear cells were able to migrate to the nerve tissue and reduce the number of seizures. Counting the number of seizures was evaluated in the pre and post-transplant record electroencephalographic (EEG) in groups EL+Saline and EL+BMMC for intensity control of seizures. Electrophysiological recordings in brain slices were done to evaluate the synaptic response using the paradigm of paired pulse stimulation. Our results show a gradual reduction in seizure frequency over a period of 240 days reaching 50%. To compare our findings to reduce crises we study the brain electrical activity by recording EEG in which we observed a higher intensity of ictal phase in EL+Saline group compared with the group EL+BMMC. We observed that the animals in the EL+Saline showed a significantly higher neuronal excitability compared to the control group and EL+BMMC proving the therapeutic effect of BMC. In the study of stimulus condition we saw that the three groups were facilitated induction of longterm potentiation (LTP) with a greater amplitude of excitatory postsynaptic potential in the group EL+Saline. Based on data obtained in this study, we conclude that the mononuclear bone marrow may have therapeutic effect on epilepsy genetics in the mouse model of EL/Suz.