Intrahippocampal injection of endothelin-1 in immature rats results in neuronal death, development of epilepsy and behavioral abnormalities later in life
Language English Country France Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16836644
DOI
10.1111/j.1460-9568.2006.04910.x
PII: EJN4910
Knihovny.cz E-resources
- MeSH
- Cerebral Arteries drug effects physiopathology MeSH
- Stroke chemically induced complications physiopathology MeSH
- Nerve Degeneration chemically induced pathology physiopathology MeSH
- Electroencephalography drug effects MeSH
- Endothelin-1 adverse effects MeSH
- Epilepsy chemically induced physiopathology MeSH
- Hippocampus drug effects pathology physiopathology MeSH
- Rats MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Hypoxia-Ischemia, Brain chemically induced complications physiopathology MeSH
- Cerebrovascular Circulation drug effects MeSH
- Animals, Newborn MeSH
- Infant, Newborn MeSH
- Memory Disorders chemically induced physiopathology MeSH
- Rats, Wistar MeSH
- Drug Administration Schedule MeSH
- Vasoconstrictor Agents adverse effects MeSH
- Age Factors MeSH
- Developmental Disabilities chemically induced physiopathology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Endothelin-1 MeSH
- Vasoconstrictor Agents MeSH
The direct injection of endothelin-1 (ET-1) into brain parenchyma was recently suggested as a suitable model of stroke. The present study was designed to assess whether intrahippocampal injection of ET-1 in immature rats causes neurodegeneration and immediate seizures, and results in impairment of motor development, cognitive decline, epilepsy and chronic hippocampal lesion. ET-1 was injected unilaterally into the dorsal hippocampus in doses of 20 or 40 pmol at the age of 12 (P12) or 25 (P25) days. Video-electroencephalographic monitoring performed during 100 min after the injection of ET-1 demonstrated the development of convulsive epileptic seizures in 75-100% of animals of individual age-and-dose groups. Long-term behavioral follow-up did not reveal impairment of motor development in any dose-and-age group. At 2 months after ET-1 injection, impairment of spatial memory occurred only in rats with 40 pmol of ET-1 at P12. At 3 months after ET-1 injection spontaneous electrographic seizures occurred in 62.5-100% animals of both ages with no relation to the dose used. Seizures were always non-convulsive. The total seizure duration per 24 h was higher in the P12 than the P25 group, suggesting more severe epilepsy. The extent of the hippocampal lesion increased with the dose of ET-1 and was significantly higher in the P12 than the P25 group. The severity of the ET-1-induced lesion correlated positively with total seizure duration per 24 h at both ages. Our results document that early intrahippocampal injection of ET-1 results in lesion development and both immediate seizures and chronic epilepsy in either age group. Cognitive impairment occurred only in rats with ET-1 injection at P12.
References provided by Crossref.org
Epilepsy Research in the Institute of Physiology of the Czech Academy of Sciences in Prague
