Deneysel Epilepsi Modelleri
Özet
Epilepsi, beyindeki nöronların aşırı elektriksel deşarjları sonucu gelişen yaygın bir nörolojik hastalık olup patofizyolojisinin temelinde inhibitör GABA ve eksitatör glutamat nörotransmitterleri arasındaki dengenin bozulması yatmaktadır. Mevcut antiepileptik ilaçların hastaların yaklaşık yüzde otuzunda yetersiz kalması ve yüksek maliyet gibi yan etkileri nedeniyle hastalığın altında yatan hücresel mekanizmaları aydınlatacak yeni tedavi yaklaşımlarına ihtiyaç duyulmaktadır. Bu amaçla klinik ortamı taklit eden çeşitli in vitro ve in vivo deneysel epilepsi hayvan modelleri geliştirilmiştir. Bu modeller genel olarak parsiyel ve jeneralize olmak üzere iki gruba ayrılmakta; kendi içlerinde akut ve kronik alt tiplere sahip olmaktadır. Araştırmalarda sıçan ve fare gibi kemirgenler sıklıkla tercih edilirken en popüler yöntemler arasında pentilentetrazol, pilokarpin, kainik asit ve penisilin gibi kimyasal konvülzan ajanların kullanımı yer almaktadır. Kimyasal yöntemlerin yanı sıra elektriksel kindling, maksimal elektroşok ve kendi kendine devam eden status epileptikus gibi elektriksel stimülasyon modelleri ile çeşitli iyon kanalı mutasyonlarını inceleyen genetic modeller de mevcuttur. Her modelin kendine özgü avantajları ve dezavantajları bulunduğundan araştırmacıların test edecekleri terapötik stratejiye en uygun protokolü titizlikle seçmesi, etkili tedavi yöntemlerinin geliştirilmesi açısından kritik önem taşımaktadır.
Epilepsy is a common neurological disorder caused by excessive electrical discharges of neurons in the brain, and its pathophysiology is based on the disruption of the balance between the inhibitory GABA and excitatory glutamate neurotransmitters. Since current antiepileptic drugs remain ineffective in approximately thirty percent of patients and carry side effects such as high costs, new therapeutic approaches are needed to elucidate the underlying cellular mechanisms of the disease. For this purpose, various in vitro and in vivo experimental animal models of epilepsy that mimic the clinical environment have been developed. These models are generally classified into two groups as partial and generalized, with acute and chronic subtypes. While rodents like rats and mice are frequently preferred in studies, the most popular methods include the use of chemical convulsant agents such as pentylenetetrazol, pilocarpine, kainic acid, and penicillin. In addition to chemical methods, electrical stimulation models such as electrical kindling, maximal electroshock, and self-sustaining status epilepticus, as well as genetic models examining various ion channel mutations, are also available. Since each model has its own advantages and disadvantages, it is critically important for researchers to meticulously select the most appropriate protocol for the therapeutic strategy they will test in order to develop effective treatment methods.
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