Summary Purpose Rapamycin (RAP) has certain antiepileptogenic features. However, it is unclear whether these effects can be explained by the anticonvulsant action of RAP, which has not been studied yet. To address this question, we tested potential anticonvulsant effects of RAP in immature and adult rats using different seizure models and treatment paradigms. In addition, we studied changes in the expression of neuropeptide Y (NPY) induced by RAP, which may serve as an indirect target of the RAP action. Methods A complex approach was adopted to evaluate the anticonvulsant potential of RAP: We used flurothyl-, pentylenetetrazole (PTZ)-, NMDA-, and kainic acid (KA)-induced seizures to test the effects of RAP using different pretreatment protocols in immature and adult rats. We also evaluated expression of NPY within the primary motor cortex, hippocampal CA1, and dentate gyrus (DG) after different pretreatments with RAP in immature rats. Key findings We found that (1) RAP administered with short-term pretreatment paradigms has a weak anticonvulsant potential in the seizure models with compromised inhibition. (2) Lack of RAP efficacy correlates with decreased NPY expression in the cortex, CA1 and DG. Specifically in immature rats, a single dose of RAP (3 mg/kg) four or 24 hrs prior to seizure testing had anticonvulsant effects against PTZ-induced seizures. In the flurothyl seizure model only the four-hour pretreatment with RAP was anticonvulsant in the both age groups. Short-term pretreatments with RAP had no effects against NMDA- and KA-induced seizures tested in immature rats. Long-term pretreatments with RAP over eight days did not show beneficial effect in all tested seizure models in developing rats. Moreover, the long-term pretreatment with RAP had a slight proconvulsant effect on KA-induced seizures. In immature rats, any lack of anticonvulsant effect (including proconvulsant effect of multiple doses of RAP) was associated with downregulation of NPY expression in the cortex and DG. In immature animals, after a single dose of RAP with 24 hrs delay, we found a decrease of NPY expression in CA1 and DG. Significance Our data show a weak age-, treatment paradigm-, and model-specific anticonvulsant effects of RAP as well as loss of those effects after long-term RAP pretreatment associated with downregulation of NPY expression. These findings suggest that RAP is a poor anticonvulsant and may have beneficial effects only against epileptogenesis. In addition, our data present new insights into mechanisms of RAP action on seizures indicating a possible connection between mTOR signaling and NPY system.

SUMMARYInfantile spasms (IS) is a devastating epilepsy syndrome of childhood. IS occurs in 3-12-month-old infants and is characterized by spasms, interictal electroencephalography (EEG) hypsarrhythmia, and profound mental retardation. Hormonal therapy [adrenocorticotropic hormone (ACTH), corticosteroids] is frequently used, but its efficacy is tainted by severe side effects. For research of novel therapies, a validated animal model of IS is required. We propose the model of spastic seizures triggered by N-methyl-D-aspartate (NMDA) in infant rats prenatally exposed to betamethasone. The spasms have remarkable similarity to human IS, including motor flexion spasms, ictal EEG electrodecrement, and responsiveness to ACTH. Interestingly, the spasms do not involve the hippocampus. Autoradiographic metabolic mapping as well as tagging of the areas of neuronal excitation with c-fos indicates a strong involvement of hypothalamic structures such as the arcuate nucleus, which has significant bilateral connections with other hypothalamic nuclei as well as with the brainstem.

ÖZETServikal ektopik gebelik endoservikal bölgeye implante olan, yüksek maternal morbidite ve mortalite ile seyreden nadir bir durumdur. Erken tanı ve tedavi bu hastalarda fertilitenin korunması ile birlikte hayat kurtarıcı olabilmektedir. Bu yazıda endoservikal küretaj ile sonlandırılan ve kanama kontrolü amacıyla intraservikal foley uygulanarak başarılı bir şekilde tedavi edilen bir servikal ektopik gebelik olgusu literatür eşliğinde sunulmuştur.Anahtar kelimeler: Servikal ektopik gebelik, tanı, tedavi. ABSTRACTCervical ectopic pregnancy which is implanted in the endocervical region, a rare condition characterized by high maternal morbidity and mortality. Early diagnosis and treatment can be life saving with preserving fertility in these patients. In this article, diagnosis and treatment of a cervical ectopic pregnancy case is presented with the review of the literature.