The goal of this study was to develop a new model of ischemia-induced seizures in immature rats using injection of vasoconstrictor Endothelin-1 (ET-1) into the brain. ET-1 (10, 20, or 40 pmol) was infused into the left dorsal hippocampus of freely moving Wistar rats 12 (P12) and 25 (P25) days old. Animals were then video/EEG-monitored for 100 min and monitoring was repeated 22 h later. Parameters of electrographic seizures (frequency and mean duration) as well as pattern of their behavioral correlates were evaluated. The pattern of behavioral seizures was used to develop model-specific scoring system. Cresyl violet and Fluoro Jade-B-staining were used to evaluate brain damage. Extension of the lesion was correlated with seizure severity. After ET-1-injection, seizures occurred in 83-100% animals of all age-and-dose groups and persisted for 24 h except P12 rats with 10 pmol. There were no differences in average seizure duration (18-40 s) or seizure frequency (3-7 seizures/100 min) among individual dose-groups. Between the 1st and 2nd observation period, total seizure duration decreased in 71% of P12 and 47% of P25 rats. Electrographic seizure activity was most frequently accompanied by clonus, incidence of more severe convulsions (barrel rolling or generalized clonic seizures) increased with dose of ET-1. Morphologic examination did not reveal any dose-related difference in damage severity, hippocampal damage was however more extensive in P12 compared to P25 animals. Seizure severity correlated positively with severity of the damage in both age groups. Our study presents focal injection of ET-1 into the brain as a new and practical model of ischemia-induced seizures in immature rats.

• MeSH
• elektroencefalografie statistika a číselné údaje   MeSH
• endotelin-1 aplikace a dávkování   farmakologie   MeSH
• epilepsie chemicky indukované   patofyziologie   patologie   MeSH
• financování organizované MeSH
• hipokampus patofyziologie   patologie   účinky léků   MeSH
• injekce MeSH
• ischemie mozku chemicky indukované   patofyziologie   patologie   MeSH
• krysa rodu rattus MeSH
• novorozená zvířata MeSH
• potkani Wistar MeSH
• videozáznam MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata 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.

• MeSH
• arteriae cerebrales patofyziologie   účinky léků   MeSH
• cévní mozková příhoda chemicky indukované   komplikace   patofyziologie   MeSH
• degenerace nervu chemicky indukované   patofyziologie   patologie   MeSH
• elektroencefalografie účinky léků   MeSH
• endotelin-1 škodlivé účinky   MeSH
• epilepsie chemicky indukované   patofyziologie   MeSH
• financování organizované MeSH
• hipokampus patofyziologie   patologie   účinky léků   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• mozková hypoxie a ischemie chemicky indukované   komplikace   patofyziologie   MeSH
• mozkový krevní oběh účinky léků   MeSH
• novorozená zvířata MeSH
• novorozenec MeSH
• poruchy paměti chemicky indukované   patofyziologie   MeSH
• potkani Wistar MeSH
• rozvrh dávkování léků MeSH
• vazokonstriktory škodlivé účinky   MeSH
• věkové faktory MeSH
• vývojové poruchy u dětí chemicky indukované   patofyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• zvířata MeSH