Prostaglandin E(2) potentiates methylmalonate-induced seizures.

Abstract:

PURPOSE:Methylmalonic acidemias are inherited metabolic disorders characterized by methylmalonate (MMA) accumulation and neurologic dysfunction, including seizures. It is known that metabolic crises in affected patients are precipitated by infections. Although growing evidence supports that inflammation facilitates seizures, it is not known whether inflammatory mediators facilitate MMA-induced seizures. Therefore, in this study we investigate the involvement of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) in MMA-induced seizures. METHODS:Adult male Wistar rats were implanted with electrodes over the parietal cortex for electroencephalography (EEG) recording and a cannula in the right lateral ventricle. Animals were injected with PGE(2) (100 ng/2 μl, i.c.v.) or phosphate-buffered saline (PBS) (2 μl, i.c.v.), 15 min before MMA (2.5 μmol/2.5 μl, i.c.v.) or NaCl (2.5 μmol/2.5 μl, i.c.v.). The anticonvulsant effect of celecoxib (0.2; 2 or 20 mg/kg, p.o., 60 min before MMA) on MMA-induced seizures, and whether PGE(2) (10 or 100 ng/2 μl, i.c.v.) prevented the anticonvulsant effect of celecoxib (2 mg/kg, p.o.) were also investigated. KEY FINDINGS:PGE(2) decreased the latency to MMA-induced jerks and generalized seizures, and increased the amplitude of generalized seizure EEG recordings. The selective COX-2 inhibitor celecoxib at the dose 2 mg/kg, but not at the dose 20 mg/kg, completely prevented MMA-induced seizures. The protective effect of celecoxib (2 mg/kg) against MMA-induced seizures was prevented by PGE(2). SIGNIFICANCE:These results support a role for PGE(2) in the seizures elicited by MMA, which is in agreement with the view that infections may precipitate and exacerbate neurologic dysfunction in patients with MMA acidemic.

journal_name

Epilepsia

journal_title

Epilepsia

authors

Salvadori MG,Banderó CR,Jesse AC,Gomes AT,Rambo LM,Bueno LM,Bortoluzzi VT,Oliveira MS,Mello CF

doi

10.1111/j.1528-1167.2011.03326.x

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

189-98

issue

1

eissn

0013-9580

issn

1528-1167

journal_volume

53

pub_type

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