Öz
Background: Pentylenetetrazol (PTZ) is the predominantly used chemical in studies to develop antiepileptic drugs and to investigate the mechanism of epilepsy. As PTZ is given systematically, it leads to generalized seizures, first creating myoclonic contractions and following generalized tonic-clonic seizures. According to the kindling model of epilepsy, repeated chemical stimulation to animals causes electrophysiological changes in local tissue. It was aimed to better observe and score the seizures of experimental animals by placing intermediate-phase levels between the phases.
Materials and Methods: The study was performed by intraperitoneal administration of PTZ to female (n=7) and male (n=7) Wistar-Albino rats. PTZ agent administered at a dose of 35 mg/kg every two days allowed the model to kindle at a final dose of 50 mg/kg at the end of one month. The seizures were scored according to the Racine scoring method and recorded on video.
Results: According to the results, there was a significant difference between phase values of original Racine scoring and those of new suggested Racine scoring for both female and male epilepsy groups
Conclusions: The importance of the developed method is to determine a more valid and more useful model by adding intermediate levels to all grades of the animal model proposing to change the degree of scoring in the literature.
Anahtar Kelimeler
Destekleyen Kurum
Yozgat Bozok University
Proje Numarası
6602c-TF/19-299
Teşekkür
To Arda Kaan Uner for organizing the manuscript.
Kaynakça
- 1. Thijs RD, Surges R, O'Brien TJ, Sander JW. Epilepsy in adults. Lancet. 2019; 393(10172):689-701.
- 2. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014; 55(4): 475-82.
- 3. Dhir A. Pentylenetetrazol (PTZ) kindling model of epilepsy. Curr Protoc Neurosci. 2012; 58(1):9-37.
- 4. Marangoz C. Deneysel epilepsi modelleri. OMÜ Tıp Dergisi. 1997; 14:147-186.
- 5. da Silva LF, Pereira P, Elisabetsky E. A neuropharmacological analysis of PTZ-induced kindling in mice. Gen Pharmacol. 1998; 31(1): 47-50.
- 6. Shimada T, Yamagata K. Pentylenetetrazole-Induced Kindling Mouse Model. J Vis Exp. 2018; 136:e56573.
- 7. Lüttjohann A, Fabene PF, van Luijtelaar G. A revised Racine's scale for PTZ-induced seizures in rats. Physiol Behav. 2009; 98(5):579-86.
- 8. Van Erum J, Van Dam D, De Deyn PP. PTZ-induced seizures in mice require a revised Racine scale. Epilepsy Behav. 2019; 95:51-55. 9. McIntyre DC, Poulter MO, Gilby K. Kindling: some old and some new. Epilepsy Res. 2002; 50(1-2):79-92.
- 10. Garcia-Cairasco N, Doretto MC, Prado RP, Jorge BPD, Terra VC, Oliveira JAC. New insights into behavioral evaluation of audiogenic seizures. A comparison of two ethological methods. Behavioural brain research. 1992; 48(1):49-56.
- 11. Van Erum J, Valkenburg F, Van Dam D, De Deyn PP. Pentylenetetrazole-induced Seizure Susceptibility in the Tau58/4 Transgenic Mouse Model of Tauopathy. Neuroscience. 2020; 425:112-122.
- 12. Luszczki J, Wojcik-Cwikla J, Andres M, Czuczwar SJ. Pharmacological and Behavioral Characteristics of Interactions between Vigabatrin and Conventional Antiepileptic Drugs in Pentylenetetrazole-Induced Seizures in Mice: An Isobolographic Analysis. Neuropsychopharmacol. 2005; 30: 958–973.
- 13. Bertoncello KT, Aguiar GPS, Oliveira JV, Siebel AM. Micronization potentiates curcumin’s anti-seizure effect and brings an important advance in epilepsy treatment. Sci Rep 2018; 8: 2645.
- 14. Racine Ronald J. Modification of seizure activity by electrical stimulation: II. Motor seizure. Electroencephalography and clinical neurophysiology 1972; 32(3): 281-294.
Öz
Amaç: Pentilentetrazol (PTZ), antiepileptik ilaçlar geliştirmek ve epilepsi mekanizmasını araştırmak için çalışmalarda ağırlıklı olarak kullanılan kimyasaldır. PTZ sistematik olarak verildiğinden, ilk önce miyoklonik kasılmalar yaratarak genelleşmiş tonik-klonik nöbetleri takiben genel nöbetlere yol açar. Epilepsi tutuşma modeline göre, hayvanlara tekrarlanan kimyasal ile stimülasyon, lokal dokuda elektrofizyolojik değişikliklere neden olur.
Materyal ve Metod: Çalışma dişi (n=7) ve erkek (n=7) Wistar-Albino sıçanlarına intraperitoneal PTZ uygulaması gerçekleştirildi. İki günde bir 35 mg/kg'lık bir dozda uygulanan PTZ ajanı, modelin 1 ayın sonunda 50 mg/kg'lık son dozda tutuşmasını sağladı. Nöbetler Racine skorlama sistemine göre puanlandı ve videoya kaydedildi. Fazlar arasına ara-faz seviyeleri eklenerek deney hayvanlarının nöbetlerinin daha iyi gözlemlenmesi ve puanlandırılması amaçlanmıştır.
Bulgular: Sonuçlara göre hem dişi hem de erkek epilepsi gruplarında önceki Racine skorlama sistemindeki analize göre anlamlı bir fark vardı.
Sonuç: Geliştirilen yöntemin önemi, hayvan modelinin tüm derecelerine ara seviyeler ekleyerek daha geçerli ve kullanışlı bir model belirlemektir.
Anahtar Kelimeler
Proje Numarası
6602c-TF/19-299
Kaynakça
- 1. Thijs RD, Surges R, O'Brien TJ, Sander JW. Epilepsy in adults. Lancet. 2019; 393(10172):689-701.
- 2. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014; 55(4): 475-82.
- 3. Dhir A. Pentylenetetrazol (PTZ) kindling model of epilepsy. Curr Protoc Neurosci. 2012; 58(1):9-37.
- 4. Marangoz C. Deneysel epilepsi modelleri. OMÜ Tıp Dergisi. 1997; 14:147-186.
- 5. da Silva LF, Pereira P, Elisabetsky E. A neuropharmacological analysis of PTZ-induced kindling in mice. Gen Pharmacol. 1998; 31(1): 47-50.
- 6. Shimada T, Yamagata K. Pentylenetetrazole-Induced Kindling Mouse Model. J Vis Exp. 2018; 136:e56573.
- 7. Lüttjohann A, Fabene PF, van Luijtelaar G. A revised Racine's scale for PTZ-induced seizures in rats. Physiol Behav. 2009; 98(5):579-86.
- 8. Van Erum J, Van Dam D, De Deyn PP. PTZ-induced seizures in mice require a revised Racine scale. Epilepsy Behav. 2019; 95:51-55. 9. McIntyre DC, Poulter MO, Gilby K. Kindling: some old and some new. Epilepsy Res. 2002; 50(1-2):79-92.
- 10. Garcia-Cairasco N, Doretto MC, Prado RP, Jorge BPD, Terra VC, Oliveira JAC. New insights into behavioral evaluation of audiogenic seizures. A comparison of two ethological methods. Behavioural brain research. 1992; 48(1):49-56.
- 11. Van Erum J, Valkenburg F, Van Dam D, De Deyn PP. Pentylenetetrazole-induced Seizure Susceptibility in the Tau58/4 Transgenic Mouse Model of Tauopathy. Neuroscience. 2020; 425:112-122.
- 12. Luszczki J, Wojcik-Cwikla J, Andres M, Czuczwar SJ. Pharmacological and Behavioral Characteristics of Interactions between Vigabatrin and Conventional Antiepileptic Drugs in Pentylenetetrazole-Induced Seizures in Mice: An Isobolographic Analysis. Neuropsychopharmacol. 2005; 30: 958–973.
- 13. Bertoncello KT, Aguiar GPS, Oliveira JV, Siebel AM. Micronization potentiates curcumin’s anti-seizure effect and brings an important advance in epilepsy treatment. Sci Rep 2018; 8: 2645.
- 14. Racine Ronald J. Modification of seizure activity by electrical stimulation: II. Motor seizure. Electroencephalography and clinical neurophysiology 1972; 32(3): 281-294.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Proje Numarası | 6602c-TF/19-299 |
| Yayımlanma Tarihi | 20 Ağustos 2020 |
| Gönderilme Tarihi | 3 Temmuz 2020 |
| Kabul Tarihi | 17 Ağustos 2020 |
| Yayımlandığı Sayı | Yıl 2020 Cilt: 17 Sayı: 2 |
Cited By
The Aqueous Lyophilisate of Alchemilla Kiwuensis Engl. (Rosaceae) Displays Antiepileptogenic and Antiepileptic Effects on PTZ-induced Kindling in rats: Evidence of Modulation of Glutamatergic and GABAergic Pathways Coupled to Antioxidant Properties
Neurochemical Research
https://doi.org/10.1007/s11064-023-03982-0
Harran Üniversitesi Tıp Fakültesi Dergisi / Journal of Harran University Medical Faculty