| dc.description.abstract | Epilepsy is one of the most common chronic neurological diseases, characterized by recurrent
epileptic seizures, where one-third of patients are refractory to existing treatments. Evidences have
revealed association between neuroinflammation and increased susceptibility to seizures since there is
a pronounced increase in the expression of key inflammatory mediators, such as prostaglandin E2
(PGE2) during seizures. The PGE2 has been demonstrated to stimulate the release of glutamate and to
inhibit Na+ K+ -ATPase enzyme, which in fact may increase neuronal excitability, contributing to
seizure. Knowing the important role of inflammation during seizures and existence of refractory to
anticonvulsant treatment, the purpose initial of the present study was to investigate whether PGE2
increases to susceptibility to seizures induced by pentylenetetrazol (PTZ). Subsequently, we evaluate
whether a compound isolated from the Piper aleyreanum plant, named Galangin, proved to be anti-
inflammatory and protective in a nociception model induced by glutamate and PGE2, could have
anticonvulsive activity in this study. For this, in the experiment 1, the mice were injected with PGE2
(100ng/2μl; intracerebroventricular (i.c.v.) and fifteen minutes later were injected with a subefective
PTZ dose (35mg/kg, intraperitoneal (i.p) for evaluation of susceptibility to seizures. In the experiment
2, the mice were injected with Galangin (30mg/kg; i.p.) fifteen minutes before PGE2 injection, fifteen
minutes later were injected with PTZ, in the same doses. Our results showed that the group treated
com PGE2 increased the susceptibility to PTZ, causing myoclonic and generalized seizures, increasing
the seizures duration and electroencephalographic wave amplitude. Furthermore, statistical analyzes
showed that the treatment with PGE2 or PGE2 and PTZ combined increased IBA-1 (microglial
marker), GFAP (astrocytic marker), 4-HNE (lipid peroxidation marker), VCAM-1 (vascular cell
adhesion molecule 1) and p-PKAIIα (phosphorylated cAMP-dependent protein kinase)
immunocontents. However, nor PTZ or PGE2 treatment changed the immunocontent of receptors of
PGE2 (EP1, EP2 and EP3). Indeed, pre-treatment with Galangin prevented the convulsive behavior
and decreased electroencephalographic wave amplitude as well as prevented reactive species
production, microglial and astrocytic activation, decreased VCAM-1 immunocontent and
phosphorylation state of PKAIIα induced by PGE2/PTZ. Therefore, this study suggests that the
compound Galangin presented anticonvulsive and anti-inflammatory activities against the behavioral
and neurochemical changes induced by administration of PGE2 and PTZ. However, further studies are
needed to investigate the clinical implications of these findings and their underlying mechanisms. | |
