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Brain‐derived neurotrophic factor superinduction parallels anti‐epileptic−neuroprotective treatment in the pilocarpine epilepsy model
Author(s) -
Biagini Giuseppe,
Avoli Massimo,
Marcinkiewicz Jadwiga,
Marcinkiewicz Mieczyslaw
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00163.x
Subject(s) - pilocarpine , status epilepticus , diazepam , epilepsy , neuroprotection , hippocampus , neurotrophic factors , pentobarbital , pharmacology , intraperitoneal injection , hippocampal formation , medicine , brain derived neurotrophic factor , endocrinology , anticonvulsant , neurotrophin , anesthesia , neuroscience , psychology , receptor
Antiepileptic drugs provide neuroprotection in several animal models of brain damage, including those induced by status epilepticus (SE). The mechanisms involved in this action are unknown, but neurotrophic factors such as brain‐derived neurotrophic factor (BDNF) may play a role. In this study we investigated the changes in BDNF levels in rats in which SE had been induced by pilocarpine injection (400 mg/kg i.p.) and continued for several hours (unprotected group). In other animals (protected groups), SE was suppressed after 30 min by intraperitoneal injection of either diazepam (10 mg/kg) + pentobarbital (30 mg/kg) or paraldehyde (0.3 mg/kg). In diazepam + pentobarbital‐treated rats the hippocampal damage caused by SE was significantly lower ( p < 0.05) than in unprotected animals. In addition, 2 and 24 h after pilocarpine injection, the levels of BDNF mRNA were moderately increased in the unprotected group, but ‘superinduced’ in protected animals, especially in the neocortex and hippocampus. A time‐dependent increase in BDNF immunoreactivity was also found by western blot analysis in rats treated with diazepam + pentobarbital. In contrast, a decrease of BDNF immunoreactivity occurred in the unprotected group. In conclusion, these results show that neuroprotection induced by anti‐epileptic drugs in pilocarpine‐treated rats is accompanied by strong potentiation of BDNF synthesis in brain regions involved in SE.