Velísek Libor, Velísková Jana, Giorgi Filippo S, Moshé Solomon L
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Exp Neurol. 2006 Sep;201(1):203-11. doi: 10.1016/j.expneurol.2006.04.005. Epub 2006 May 30.
The substantia nigra pars reticulata (SNR) plays an important age- and sex-specific role in control of clonic seizures. Its involvement in control of tonic-clonic seizures is contradictory. We investigated the role of the SNR in the tonic-clonic seizures induced in male, female and neonatally castrated male rats using flurothyl. In adult female rats, vaginal impedance determined the changes in progesterone/estrogen ratio. Rats at various postnatal ages received infusions of muscimol or vehicle in the SNRanterior or SNRposterior. Furthermore, in 15-day-old (P15) and adult male rats, ZAPA (a GABA(A) receptor agonist) or AP7 (an NMDA receptor antagonist) was infused. The developmental profile of tonic-clonic seizure threshold differed between male and female rats possibly due to early postnatal testosterone surge in male rats. On the other hand, changing estrogen/progesterone ratio in cycling adult female rats had no effect on seizure threshold. Intranigral muscimol had proconvulsant effects on tonic-clonic seizures only in immature rats, and this effect was dependent on the perinatal testosterone surge. ZAPA had anticonvulsant effects in P15 rats but was not effective in adult rats. Only AP7 had anticonvulsant effects in both adult and P15 rats. Results indicate that thresholds for flurothyl-induced tonic-clonic seizures develop under the control of postnatal testosterone. Although GABAergic inhibition in the SNR affects tonic-clonic seizures in developing rats, only the NMDA antagonist had consistent anticonvulsant effects throughout development.
黑质网状部（SNR）在阵挛性癫痫的控制中发挥着重要的年龄和性别特异性作用。其在强直阵挛性癫痫控制中的作用存在矛盾。我们使用三氟乙烷研究了SNR在雄性、雌性和新生期去势雄性大鼠中诱导的强直阵挛性癫痫中的作用。在成年雌性大鼠中，阴道阻抗决定了孕酮/雌激素比值的变化。不同出生后年龄的大鼠在SNR前部或SNR后部接受了蝇蕈醇或赋形剂的输注。此外，在15日龄（P15）和成年雄性大鼠中，输注了ZAPA（一种GABA(A)受体激动剂）或AP7（一种NMDA受体拮抗剂）。强直阵挛性癫痫阈值的发育情况在雄性和雌性大鼠之间有所不同，这可能归因于雄性大鼠出生后早期的睾酮激增。另一方面，成年雌性大鼠周期性变化的雌激素/孕酮比值对癫痫阈值没有影响。脑内注射蝇蕈醇仅对未成熟大鼠的强直阵挛性癫痫有促惊厥作用，且这种作用依赖于围产期的睾酮激增。ZAPA在P15大鼠中有抗惊厥作用，但在成年大鼠中无效。只有AP7在成年和P15大鼠中都有抗惊厥作用。结果表明，三氟乙烷诱导的强直阵挛性癫痫阈值在出生后睾酮的控制下发展。虽然SNR中的GABA能抑制影响发育中大鼠的强直阵挛性癫痫，但只有NMDA拮抗剂在整个发育过程中具有一致的抗惊厥作用。
