Korean J Physiol Pharmacol.  2013 Feb;17(1):15-21. 10.4196/kjpp.2013.17.1.15.

Influence of Aspirin on Pilocarpine-Induced Epilepsy in Mice

• Jeong KH
• Kim JY
• Choi YS
• Lee MY
• Kim SY

• KMID: 1432758
• DOI: http://doi.org/10.4196/kjpp.2013.17.1.15

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.

Keyword

Aspirin; Hippocampus; Mice; Seizure susceptibility; Status epilepticus

MeSH Terms

Animals
Aspirin
Benzoxazines
Cell Death
Epilepsy
Epilepsy, Temporal Lobe
Fluoresceins
Hippocampus
Humans
Immunohistochemistry
Mice
Nervous System Diseases
Neurons
Pilocarpine
Seizures
Status Epilepticus
Viola
Aspirin
Benzoxazines
Fluoresceins
Pilocarpine

Figure

• 

  Fig. 1 Effects of aspirin on onset time of SE and mortality after pilocarpine-induced SE. (A) The onset time of SE was significantly shorter in the 150 mg/kg aspirin-treated group compared to the vehicle-treated group. (B) The mortality was increased in aspirin-treated groups after SE. Veh, vehicle-treated group; ASA 15, aspirin (15 mg/kg)-treated group; ASA 150, aspirin (150 mg/kg)-treated group. Data are presented as the mean±SEM. *p<0.05 compared to Veh.

• 

  Fig. 2 Aspirin does not affect neuronal death in the mouse hippocampus after pilocarpine-induced SE, as evaluated by cresyl violet staining. Compared with normal control mice (A~C), many pyknotic cells were observed 7 days after SE in the hippocampal CA1 and CA3 areas of mice treated with vehicle (D~F). SE-induced cell death in the hippocampal CA1 and CA3 sub-regions in mice treated with aspirin of 15 mg/kg (G~I) or 150 mg/kg (J~L) were similar with those in vehicle-treated animals (D~F). Con, normal control group; Veh, vehicle-treated group; ASA 15, aspirin (15 mg/kg)-treated group; ASA 150, aspirin (150 mg/kg)-treated group. Scale bar=200 µm (A, D, G, J) or 50 µm (B, C, E, F, H, I, K, L).

• 

  Fig. 3 Aspirin is not neuroprotective in the hippocampus after pilocarpine-induced SE. No Fluoro-Jade signal was observed in the hippocampus of normal control mice (A~C). Representative photomicrographs of Fluoro-Jade staining show degenerating neurons in the hippocampus of vehicle- (D) and aspirin-treated (G, J) mice. A number of Fluoro-Jade-positive cells were detected in the CA1 or CA3 areas of vehicle- (E, F), 15 mg/kg aspirin- (H, I), and 150 mg/kg aspirin- (K, L) treated mice. Con, normal control group; Veh, vehicle-treated group; ASA 15, aspirin (15 mg/kg)-treated group; ASA 150, aspirin (150 mg/kg)-treated group. Scale bar=200 µm (A, D, G, J) or 50 µm (B, C, E, F, H, I, K, L).

• 

  Fig. 4 Aspirin does not affect glial responses in the hippocampus after pilocarpine-induced SE. GFAP (A, C, E, G) and Iba-1 (B, D, F, H) were used as markers for reactive astrocytes and activated microglia, respectively. Seven days after SE, GFAP-positive and Iba-1-positive cells were broadly expressed in the hippocampus of vehicle-treated mice (C, D) compared with normal control (A, B). Expression of GFAP and Iba-1 were similarly observed in mice treated with 15 mg/kg aspirin (E, F) or 150 mg/kg aspirin (G, H) compared to mice treated with vehicle (C, D). Con, normal control group; Veh, vehicle-treated group; ASA 15, aspirin (15 mg/kg)-treated group; ASA 150, aspirin (150 mg/kg)-treated group. Scale bar=200 µm (A~H).

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