Efeito neuroprotetor do disseleneto de difenila sobre a memória, atividade locomotora e captação de cálcio frente a trauma mecano-encefálico em ratos

Abstract

Cerebral concussion and traumatic brain injury (TBI) are a disturbance of neural function frequently induced by a sudden acceleration and deceleration forces of the head with or without skull fracture. A large number of studies have shown that the TBI is associated with various primary events like glutamate release, elevated intracellular calcium, the formation of free radicals and subsequent lipid peroxidation as well as the decrease of serum magnesium contents, behavior disturbances, like memory loss and damage on locomotor activities. Such primary events may cause secondary damage by activating endogenous autodestructive biochemical processes. Diphenyl diselenide (PhSe)2 is an organic selenium compound that has been demonstrated several biological effects that could be implicated in potential therapy to TBI. The aim of the present study was to evaluate the effects of the oral administration of (PhSe)2 on TBI rat model, using 45Ca+2 uptake in cortex, striatum and hippocampus slices and serum magnesium concentration. Moreover, there were evaluate some behavioral aspects using startle test, conditioned fear and spontaneous alternation tasks to evaluate the acquisition and facilitation of memory; open field and rota-rod task to evaluate the neurolocomotor activity. The present study there was possible to verify at dose administered an increase in 45Ca+2 uptake by cerebral cortex, striatum and hippocampus slices in animals subjected to TBI and which received (PhSe)2 treatment (100 mM 15 minutes post TBI event), especially at the pretreatment group (20 mM by 3 days and 100 mM 15 minutes post TBI event) when compared to TBI group. (PhSe)2 was effective to increase the serum magnesium levels concentration, which corroborate with its neuroprotective effect, once calcium and magnesium are present in several neurochemicals mechanism on Central Nervous System. Additionally, (PhSe)2 was able to ameliorate the acquisition and facilitation of memory in behavioral tasks performed,. Especially, when the (PhSe)2 was administered before and after to TBI. The neurolocomotor abilities were recorded at pre-training period (24h before to TBI). The behavioral changes in the open-field and rota-rod tasks were performed in 24 hours after TBI. (PhSe)2 was able to increase the locomotor activity in open-field task suggesting anxiolytic-like effect too. When (PhSe)2 was administered before and after to TBI. Finally, on rota-rod task reiterated the findings observed on open field, with a locomotor coordination response present in both (PhSe)2 treatments, once more with distinction to pretreatment. Therefore, considering the relevance of this study on the development of new drugs that can decrease the neuronal damage and improve the patients recover post TBI, decreasing sequels, our results suggest that the studies with (PhSe)2 against TBI could be more deeply investigated as a prospective pharmacological tools against TBI.