Abstract
We aimed to characterize the mechanisms involved in neuroprotection by R-PIA administered before pilocarpine-induced seizures. Caspase-1 and caspase-3 activities were assayed using fluorimetry, and cathepsin D, HSP-70, and AKT expression levels were assayed using Western Blot of hippocampal samples. R-PIA was injected before pilocarpine (PILO), and four groups were studied at 1 h 30 min and 7 days following initiation of status epilepticus (SE): PILO, R-PIA+PILO, SALINE, and R-PIA+SALINE. At 1 h 30 min, significantly higher activities of caspase-1 and -3 were observed in the PILO group than in the SALINE group. Caspase-1 and -3 activities were higher in the R-PIA+PILO group than in the PILO group. At 7 days following SE, caspase-1 and -3 activities were higher than in the initial post-seizure phase compared to the SALINE group. The pretreatment of rats receiving PILO significantly reduced caspase activities compared to the PILO group. Expression of HSP-70, AKT, and cathepsin D was significantly higher in the PILO group than in the SALINE. In the R-PIA+PILO group, the expression of AKT and HSP-70 was greater than in rats receiving only PILO, while cathepsin D presented decreased expression. Pretreatment with R-PIA in PILO-injected rats strongly inhibited caspase-1 and caspase-3 activities and cathepsin D expression. It also increased expression levels of the neuroprotective proteins HSP-70 and AKT, suggesting an important role in modulating the cellular survival cascade.
Highlights
In in the present study, we studied the role of R-PIA administered before the present study, we studied the role of R-PIA administered before pilocarpine on the modpine on the modulation pro-apoptotic factors
At seven days following status epilepticus (SE), no caspase activities were observed in any control (SALINE and R-PIA+SALINE), caspase-1 and -3 activities remained very high in the PILO group; there were reduced activities in the R-PIA+PILO group. These findings suggest that R-PIA administered before pilocarpine activates caspases-1 and -3 as early as 1 h 30 min following SE onset and inhibits apoptotic cascades and inflammation resulting from seizures 7 days later
Our findings suggest that R-PIA increased caspase activity in the initial phase of SE, and significantly reduced it 7 days later, a time in which expressive neuroprotection was observed in the hippocampus [43,44]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Epilepsy is a chronic neurologic disease that affects about 65 million people worldwide, representing a substantial proportion of patients in neurological clinics and a substantial global disease burden [1]. About 40% of patients present with temporal lobe epilepsy. Despite the growing number of antiepileptic drugs commercially available, about 30% of patients have refractory epilepsy. Hippocampal sclerosis is the most common histopathology observed in patients with mesial temporal lobe epilepsy (MTLE) [2]. Mesial temporal sclerosis (MTS) is a term used to refer to significant pathological changes involving the hippocampus and the amygdala and entorhinal cortex. A task force of the International League Against Epilepsy (ILAE), based on the cell loss patterns, classified
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