Pilot Study on the Effect of 9-phenanthrol on Brain Electrical Activity in an Experimental Epilepsy Animal Model

Öz

Background: Epilepsy is a chronic disorder characterized by recurrent seizures, affecting millions of people worldwide. The drugs used in its treatment often fail to achieve complete success in many cases, and their side effects can limit their use. For these reasons, developing new therapeutic strategies is essential. In recent studies on epilepsy, TRP channels have attracted increasing attention. The TRPM4 channel is a cation channel located in the cell membrane. It has been detected in various parts of the body, such as the brain and spinal cord, and is inhibited by 9-Phenanthrol. In our study, it was hypothesized that inhibition of the TRPM4 channel by 9-Phenanthrol might reduce neuronal excitability, thereby producing an anticonvulsant effect. Since there are only a few studies investigating the systemic use of 9-Phenanthrol in experimental animals, it was considered appropriate to conduct a pilot study with a small number of animals.

Materials and Methods: In our research, an experimental epilepsy model was induced using penicillin, and the effects of 9-Phenanthrol on brain electrical activity were observed through electrocorticography (ECoG) recordings. The effects of 9-Phenanthrol on the amplitude and frequency of epileptic seizure activity were quantified, and the obtained data were statistically analyzed.

Results: Our findings demonstrated that 9-Phenanthrol exhibited anticonvulsant effects starting from the 150th minute after administration (p=0,02). Furthermore, when the mean amplitude values of spike waves per minute were compared, a statistically significant reduction in spike wave amplitudes was observed in the 150th minute (p=0,005).

Conclusions: Our findings are consistent with those reported in the literature. Inhibition of the TRPM4 channel has been shown to produce anticonvulsant effects and to reduce the neuronal damage caused by epileptic seizures. In conclusion, the TRPM4 channel may represent a novel therapeutic target in the treatment of epilepsy.

Anahtar Kelimeler

• 9-Phenanthrol
• Electrophysiology
• Epilepsy
• TRPM4

Destekleyen Kurum

This study was supported by TÜBİTAK within the scope of the project number TÜBİTAK 2209-A 1919B012428262.

Proje Numarası

TÜBİTAK 2209-A 1919B012428262

Etik Beyan

Ethics committee approval was obtained for the study.

Deneysel Epilepsi Hayvan Modelinde 9-Fenantrol’ün Beyin Elektriksel Aktivitesine Etkisine İlişkin Pilot Çalışma

Öz

 Amaç: Epilepsi nöbetlerle meydana gelen, dünyada milyonlarca kişinin etkilendiği kronik bir hastalıktır. Hastalığın tedavisinde kullanılan ilaçlar birçok vakada tam bir başarı sağlayamamakta, ilaçların yan etkileri ilaç kullanımını sınırlandırabilmektedir. Bu nedenlerle yeni tedavi stratejilerinin geliştirilmesi elzemdir. Epilepsi hastalığına ilişkin çalışmalarda son zamanlarda TRP kanalları dikkat çekmektedir. TRPM4 kanalı, hücre zarında bulunan bir katyon kanalıdır. Beyin, omurilik gibi vücut bölümlerinde tespit edilen TRPM4 kanalı, 9-Fenantrol tarafından inhibe edilmektedir. Çalışmamızda 9-Fenantrol uygulamasının TRPM4 kanal inhibisyonu ile sinir hücrelerinde uyarılabilirliği azaltabileceği, dolayısıyla antikonvülzan etkinlik meydana gelebileceği düşünüldü. 9-Fenantrol’ün deney hayvanları üzerinde sistemik kullanımına ilişkin çok az sayıda makale bulunduğu için az sayıda hayvanla pilot çalışma yapılması uygun görüldü.

Materyal ve metod: Çalışmamızda penisilinle deneysel epilepsi modeli oluşturuldu ve 9-Fenantrol’ün beynin elektriksel aktivitesi üzerine etkileri elektrokortikografi (ECoG) kayıtları ile gözlemlendi. 9-Fenantrol’ün epileptik nöbet aktivitesinde amplitüd ve frekans üzerine olan etkileri sayısal verilere dönüştürüldü, elde edilen bu veriler istatistiksel olarak incelendi.

Bulgular: Bulgularımız 9-Fenantrol’ün uygulama sonrasında 150. dakikadan itibaren antikonvülzan etki sağladığını gösterdi (p=0,02). Ayrıca diken dalgaların bir dakikadaki ortalama amplitüd değerleri kıyaslandığında da 150. dakikada diken dalga amplitüdlerinde istatistiksel olarak anlamlı ölçüde azalma meydana geldi (p=0,005).

Sonuç: Literatürde yapılan çalışmalar ile elde ettiğimiz bulgular uyumluluk göstermektedir. TRPM4 kanalı inhibe edildiğinde antikonvülzan etkiler görülmekle beraber epileptik nöbetle meydana gelen hasarlar azaltılabilmektedir. Sonuç olarak TRPM4 kanalının epilepsi tedavisinde yeni bir terapötik hedef olabileceği düşünülmektedir.

Anahtar Kelimeler

• 9-Fenantrol
• Elektrofizyoloji
• Epilepsi
• TRPM4

Destekleyen Kurum

Bu çalışma, TÜBİTAK 2209-A 1919B012428262 başvuru numaralı proje kapsamında TÜBİTAK tarafından desteklenmiştir.

Proje Numarası

TÜBİTAK 2209-A 1919B012428262

Etik Beyan

Çalışma için Tokat Gaziosmanpaşa Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu’ndan karar no: 2024 HADYEK-10, tarih: 12.06.2024 tarihli etik kurul onayı alınmıştır.

Kaynakça

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