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Neuroprotective activity of antazoline against neuronal damage induced by limbic status epilepticus
- Source :
- Neuroscience. 120:475-484
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- Imidazoline drugs exert neuroprotective effects in cerebral ischaemia models. They also have effects against mouse cerebellar and striatal neuronal death induced by N-methyl- d -aspartate (NMDA) through the blockade of NMDA currents. Here, we investigated the effects of antazoline on NMDA toxicity and current in rat hippocampal neuronal cultures, and on an in vivo model of status epilepticus. In hippocampal cultures, antazoline (30 μM) decreased NMDA-mediated neurotoxicity and also blocked the NMDA current with voltage-dependent and fast-reversible action (inhibition by 85±3% at −60 mV). Status epilepticus was induced by injecting pilocarpine (200 nmol) directly into the right pyriform cortex of male adult rats. The rats then received immediately three consecutive i.p. injections at 30-min intervals of either PBS (control group) or antazoline at 10 mg/kg (low-dose group) or at 45 mg/kg (high-dose group). During the 6-h recording, status epilepticus lasted more than 200 min in all groups. In the high-dose group only, seizures completely ceased 1 h after the third injection of antazoline, then started again 1 h later. Rats were killed 1 week later, and Cresyl Violet-stained sections of their brain were analysed for damage quantification. On the ipsilateral side to the pilocarpine injection, pyriform cortex and hippocampal CA1 and CA3 areas were significantly protected in both antazoline-treated groups, whilst prepyriform and entorhinal cortices were only in the high-dose group. On the contralateral side to the pilocarpine injection, only the hippocampal CA3 area was significantly protected in the low-dose group, but all investigated structures were in the high-dose group. In conclusion, antazoline is a potent neuroprotective drug in different models of neuronal primary culture, as previously shown in striatal and cerebellar granule neurons [Neuropharmacology 39 (2000) 2244], and here in hippocampal neurons. Antazoline is also neuroprotective in vivo in the intra-pyriform pilocarpine-induced status epilepticus model.
- Subjects :
- Male
N-Methylaspartate
Patch-Clamp Techniques
Time Factors
Cell Count
Status epilepticus
In Vitro Techniques
Muscarinic Agonists
Hippocampal formation
Pharmacology
Hippocampus
Neuroprotection
Rats, Sprague-Dawley
Status Epilepticus
Pregnancy
Excitatory Amino Acid Agonists
medicine
Antazoline
Animals
Trauma, Nervous System
Drug Interactions
Cells, Cultured
Cerebral Cortex
Neurons
Dose-Response Relationship, Drug
business.industry
General Neuroscience
Electric Conductivity
Pilocarpine
Neurotoxicity
Electroencephalography
medicine.disease
Rats
Disease Models, Animal
medicine.anatomical_structure
Animals, Newborn
nervous system
Cerebral cortex
Anesthesia
Histamine H1 Antagonists
NMDA receptor
Female
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 03064522
- Volume :
- 120
- Database :
- OpenAIRE
- Journal :
- Neuroscience
- Accession number :
- edsair.doi.dedup.....cd60c780f92dd5d49c27296456546a8d