Pós-condicionamento com lipopolissacarídeo bacteriano em modelo animal de epilepsia de lobo temporal

Abstract

Epilepsy is a chronic neurological disease characterized by spontaneous, or reflex, recurrent seizures (SRS). About two-thirds of the affected are able to control the seizures through medicine usage. Among the refractory cases, the possibility of surgical removal of the epileptic focus exists for only a section of patients. Therefore, it is necessary to comprehend the mechanisms behind the disease evolution, called epileptogenesis, in order to revert cases or prevent the pathology. In this work, we performed a post-conditioning protocol using bacterial lipopolysaccharide (LPS) in a temporal lobe epilepsy rat model by unilateral intrahippocampal (i.h.) injection of kainic acid (KA) in order to investigate what are the alterations on the epileptogenic process when the timing of the inflammatory intervention is altered, whether they are pathogenic or pro-resolutives. The animals were divided among four experimental groups according to the content of the first injection — saline (Sal) or KA — and the second injection, three days after the first — Sal or LPS. The rats were video recorded from the 9th to the 17th day after the 1st injection for behavioral and SRS analysis. In sequence, they were submitted to the following behavioral tests: sucrose preference, marble burying, object recognition and forced swim. Afterwards, they were perfounded and marked for immunofluorescence with Fluoro Jade C, Iba-1 and GFAP. There was no difference in the intensity, frequency and duration of the SRS among the KA groups. However, the KA+Sal group presented a higher frequency of the tail chasing behavior. On the sucrose preference test, the KA+LPS group presented a lower novelty aversion, comparable to the Sal+Sal control group. Furthermore, on the object recognition test, these animals presented a higher recovery of the long term memory in relation to the KA+Sal group, up to the control level. Both groups presented an intense inflammatory process characterized by a raise on the microglia and astrocyte marking. However, the KA+Sal group presented higher neuronal death, suggesting a different profile of the immune response in relation to the KA+LPS group. These results indicate the LPS post-conditioning as capable of reducing the KA-induced neuronal damage and recovering some of the behavioral parameters. So, this is an experimental protocol of great interest in elucidating the questions about epileptogenesis and inflammation.