Long-term Pregabalin Treatment Protects Basal Cortices and Delays the Occurrence of Spontaneous Seizures in the Lithium-Pilocarpine Model in the Rat

Autor: Estelle Koning, Astrid Nehlig, Arielle Ferrandon, Véronique M. André, Marie-Aude Rigoulot
Rok vydání: 2003
Předmět:
Zdroj: Epilepsia. 44:893-903
ISSN: 1528-1167
0013-9580
DOI: 10.1046/j.1528-1157.2003.61802.x
Popis: Summary: Purpose: To determine whether a pharmacologic treatment could delay or prevent the epileptogenesis induced by status epilepticus (SE) through the protection of some brain areas, we studied the effects of the long-term exposure to pregabalin (PGB) on neuronal damage and epileptogenesis induced by lithium-pilocarpine SE. Methods: SE was induced in adult and 21-day-old (P21) rats. At 20 min after pilocarpine, rats received 50 mg/kg PGB (pilo-preg) or saline (pilo-saline). PGB treatment was given daily at the dose of 50 mg/kg for 7 days after SE and at 10 mg/kg from day 8 until killing. Neuronal damage was assessed in hippocampus and piriform and entorhinal cortices in brain sections stained with thionine and obtained from adult and P21 animals killed 6 days after SE. The number of glial fibrillary acidic protein (GFAP)-reactive astrocytes was tested by immunohistochemistry in sections adjacent to those used for cell counting. The latency to spontaneous seizures was controlled by visual observation and EEG recording. Results: PGB induced neuroprotection in layer II of piriform cortex and layers III–IV of ventral entorhinal cortex of adult rats, whereas no hippocampal region was protected. In P21 rats, damage was limited to the hilus and similar in pilo-preg and pilo-saline animals. The number of GFAP-positive astrocytes was higher in pilocarpine- than in saline-treated rats. It was decreased in pilo-preg compared with pilo-saline rats in layer II of the piriform cortex. Adult pilo-preg rats became epileptic after a longer latency (39 days) than did pilo-saline rats (22 days). Conclusions: These data underline the antiepileptogenic consequences of long-term PGB treatment, possibly mediated by the protection of piriform and entorhinal cortices in the lithium-pilocarpine model of epilepsy.
Databáze: OpenAIRE
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