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.

Institute of Physiology Academy of Sciences of the Czech Republic Vídenská 1083 Prague 4 CZ 142 20 Czech Republic

000      

00000naa 2200000 a 4500

001      

bmc09003659

003      

CZ-PrNML

005      

20111210153008.0

008      

091123s2006 fr e eng||

009      

AR

040    __

$a ABA008 $b cze $c ABA008 $d ABA008 $e AACR2

041    0_

$a eng

044    __

$a fr

100    1_

$a Matéffyová, Adéla. $7 _AN040719

245    10

$a Intrahippocampal injection of endothelin-1 in immature rats results in neuronal death, development of epilepsy and behavioral abnormalities later in life / $c Mátéffyová A, Otáhal J, Tsenov G, Mares P, Kubová H.

314    __

$a Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, Prague 4, CZ-142 20, Czech Republic

520    9_

$a 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.

650    _2

$a financování organizované $7 D005381

650    _2

$a věkové faktory $7 D000367

650    _2

$a zvířata $7 D000818

650    _2

$a novorozená zvířata $7 D000831

650    _2

$a arteriae cerebrales $x patofyziologie $x účinky léků $7 D002536

650    _2

$a mozkový krevní oběh $x účinky léků $7 D002560

650    _2

$a vývojové poruchy u dětí $x chemicky indukované $x patofyziologie $7 D002658

650    _2

$a modely nemocí na zvířatech $7 D004195

650    _2

$a vztah mezi dávkou a účinkem léčiva $7 D004305

650    _2

$a rozvrh dávkování léků $7 D004334

650    _2

$a elektroencefalografie $x účinky léků $7 D004569

650    _2

$a endotelin-1 $x škodlivé účinky $7 D019332

650    _2

$a epilepsie $x chemicky indukované $x patofyziologie $7 D004827

650    _2

$a hipokampus $x patofyziologie $x patologie $x účinky léků $7 D006624

650    _2

$a lidé $7 D006801

650    _2

$a mozková hypoxie a ischemie $x chemicky indukované $x komplikace $x patofyziologie $7 D020925

650    _2

$a novorozenec $7 D007231

650    _2

$a mužské pohlaví $7 D008297

650    _2

$a poruchy paměti $x chemicky indukované $x patofyziologie $7 D008569

650    _2

$a degenerace nervu $x chemicky indukované $x patofyziologie $x patologie $7 D009410

650    _2

$a krysa rodu Rattus $7 D051381

650    _2

$a potkani Wistar $7 D017208

650    _2

$a cévní mozková příhoda $x chemicky indukované $x komplikace $x patofyziologie $7 D020521

650    _2

$a vazokonstriktory $x škodlivé účinky $7 D014662

700    1_

$a Otáhal, Jakub $7 xx0105144

700    1_

$a Tsenov, Grigorij, $d 1980- $7 xx0103054

700    1_

$a Mareš, Pavel, $d 1937- $7 jo20000074131

700    1_

$a Kubová, Hana, $d 1959- $7 xx0036699

773    0_

$w MED00011483 $t The European journal of neuroscience $g Roč. 24, č. 2 (2006), s. 351-360 $x 0953-816X

910    __

$a ABA008 $b x $y 8

990    __

$a 20090310084605 $b ABA008

991    __

$a 20100128113144 $b ABA008

999    __

$a ok $b bmc $g 695546 $s 557792

BAS    __

$a 3

BMC    __

$a 2006 $b 24 $c 2 $d 351-360 $i 0953-816X $m European journal of neuroscience $x MED00011483

LZP    __

$a 2009-B4/ipme