Influence of Aspirin on Pilocarpine-Induced Epilepsy in Mice

Abstract

Aspirin (acetylsalicylic acid) is one of the most widely used therapeutic agents based on its pharmacological actions, including anti-inflammatory, analgesic, anti-pyretic, and anti-thrombotic effects. In this study, we investigated the effects of aspirin on seizure susceptibility and hippocampal neuropathology following pilocarpine-induced status epilepticus (SE). SE was induced by pilocarpine hydrochloride (280 mg/kg, i.p.) administration in C57BL/6 mice (aged 8 weeks). Aspirin was administered daily (15 mg/kg or 150 mg/kg, i.p.) for 10 days starting 3 days before SE, continuing until 6 days after SE. After pilocarpine injection, SE onset time and mortality were recorded. Neuronal cell death was examined using cresyl violet and Fluoro-Jade staining, and glial responses were observed 7 days post SE using immunohistochemistry. In the aspirin-treated group, the onset time of SE was significantly shortened and mortality was markedly increased compared to the control group. However, in this study, aspirin treatment did not affect SE-induced neuronal cell death or astroglial and microglial responses in the hippocampus. In conclusion, these results suggest that the safety of aspirin should be reevaluated in some patients, especially with neurological disorders such as temporal lobe epilepsy.

Indomethacin can downregulate the levels of inflammatory mediators in the hippocampus of rats submitted to pilocarpine-induced status epilepticus

“…These data reveal the dual effect of anti-inflammatory drugs in the treatment of epilepsy. In accordance with our previous results, Jeong et al ( 9 ) reported that acetylsalicylic acid treatment also leads to increased death among epileptic animals. In contrast, several authors have shown that COX2 inhibition can control P-glycoprotein (PgP) expression, improving the penetration of antiepileptic drugs into the brain and restoring the pharmacosensitivity to these drugs ( 10 , 11 ).…”

Cyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugs

“…Of note, reductions of this dose level are often required due to intolerable side effects including nausea, asthenia and fatigue [63]. Our data indicate that adding 25 mg/kg ASA (corresponding to a daily dose of 150 mg in humans [64] to the treatment with a lower dose of sunitinib (20 mg/kg) exerts similar efficacy compared to monotherapy with 40 mg/kg sunitinib (Figure 1B, Supplementary Figure S5). Thus, combinatorial treatment with ASA might be useful to decrease the sunitinib dose upfront or to maintain efficacy in patients requiring dose reductions.…”

Anti-Inflammatory Small Molecules To Treat Seizures and Epilepsy: From Bench to Bedside

“…In another study, oral administration of celecoxib (20 mg/kg) one day after a one-hour episode of lithium/pilocarpine-induced SE in rats reduces spontaneous recurrent seizures, and prevents neuronal death and microglia activation in the hippocampus [27]. Furthermore, nonselective COX inhibitor aspirin, when administered commencing hours after pilocarpine-induced SE, reduces neuronal damage in hippocampus and recurrent seizures in rats [23], whereas aspirin pre-treatment beginning three days before pilocarpine injection does not show such beneficial effects but increases the seizure susceptibility in mice [24]. …”