Intrahippocampal injection of endothelin-1 in immature rats results in neuronal death, development of epilepsy and behavioral abnormalities later in life.
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.
Mátéffyová
Adéla
A
Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, Prague 4, CZ-142 20, Czech Republic.
Otáhal
Jakub
J
Tsenov
Grygoriy
G
Mares
Pavel
P
Kubová
Hana
H
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002536:Cerebral Arteries / Q000187:drug effects / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002658:Developmental Disabilities / Q000139:chemically induced / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004569:Electroencephalography / Q000187:drug effects; D019332:Endothelin-1 / Q000009:adverse effects*; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D007231:Infant, Newborn; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000503:physiopathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000009:adverse effects
D019332:Endothelin-1; D014662:Vasoconstrictor Agents