Tese
Efeito neuroprotetor do disseleneto de difenila sobre a memória, atividade locomotora e captação de cálcio frente a trauma mecano-encefálico em ratos
Fecha
2008-12-22Autor
Oliveira, Luís Flávio Souza de
Institución
Resumen
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.