Öz
Aim: In this study, we aimed of the effects of LEC (LEC; Liposome Encapsulated Clodronate) an agent, to selectively deplete or reduce resident and systemic macrophages population during the degeneration-regeneration cycle after peripheral nerve injury. Materials-Methods: In our experiments, eight weeks old male wistar rats randomly divided into 5 groups as control (Group A), crush (Group B4 and B8) and crush+received LEC treatment (Groups C4 and C8) (n=40). Nerve crush injury model was performed on right sciatic nerve of the animals except the control group. Immediately after injury, LEC was intravenously injected after the days of postoperation 5, 10 and 15th (Group C). After 4-8 weeks following the injury, before EMG measurement was recorded than sciatic nerve dissected from Group B and C. Before and after 4-Aminophyridine (4-Ap) administration, the Compound Action Potential (CAP) were recorded with modified sucrose-gap system which is an in-vitro electrophysiological method from these branches Results: Our data show that LEC administration on damaged nerve did not significantly change CAP's parameters which are CV (CV; Conduction Velocity), amplitude of CAP, depolarization time (DT), latency and half width of CAP (p>0.05). However, LEC significantly changed the amplitude of delayed depolarization (del-dep) when occuring after administration of 4- Ap (p<0.05). Conclusion: The data obtained from this study, LEC may be reduce process of WD (Wallerian Degeneration) and accelerate functional recovery effect on remyelination after peripheral nerve injury
Anahtar Kelimeler
Kaynakça
- Ide C. Peripheral nerve regeneration. Neurosci Res, 25: 101-121, 1996
- Garbaya B, Heapec A.M, Sargueila F, Cassagnea C.Myelin synthesis in the peripheral nervous system. Prog Neurobiol 61: 267-304, 2000.
- Bruck W. The role of macrophages in Wallerian degeneration. Brain Path, 7: 741-752,1997
- Perry VH, Brown MC. Role of macrophages in peripheral nerve degeneration and repair. Bioassays, 14: 401-406, 1992
- Van Rooijen N, van Kesteren-Hendrikx. "In vivo" depletion of macrophages by liposome-mediated "suicide".Methods Enzymol. 2003;373:3-16.
- Van Rooijen N., Sanders A., Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications, J. Immunol. Methods, 174, 83-93, (1994).
- Mustafa GÜVEN, İbrahim KAHRAMAN, Filiz KOÇ, Hacer BOZDEMİR, Yakup SARICA, İsmail GÜNAY. The Effects of Oxcarbazepine on 4-Aminopyridine-Induced Afterpotentials on Isolated Rat Sural Nerves. Journal of Neurological Sciences [Turk] 2010;27:(2): 139-149.
- Guven M, Kahraman I, Güneş Y, Gunay I.: Effect of Tramadol on peripheral nerves: An in-vitro electrophysiological study on the sural and tibial nerves of the rat. Journal of Medical Science (Türkiye Klinikleri). 2011;31(1).
- Waxman SG, Ritche JM: Molecular dissection of the myelinated axon. Ann Neurol 1993:33:121-136.
- Rizzo MA, Kocsis JD, Waxman SG. Slow sodium conductances of dorsal root ganglion neurons: intraneuronal homogeneity and interneuronal heterogeneity. J Neurophysiol. 1994 Dec;72(6):2796-815.
- Honmou, O., Utzschneider, D.A., Rizzo, M.A., Bowe, C.M., Waxman, S.G., Kocsis, J.D.,. Delayed depolarization and slow sodium currents in cutaneous afferents. J. Neurophysiol. 1994;71:1627–1637.
- Nonaka T, Honmou O, Sakai J, Hashi K, Kocsis JD. Excitability changes of dorsal root axons following nerve injury: implications for injury-induced changes in axonal Na+ channels. Brain Research. 2000;859:280-285.
- Kocsis JD and Waxman SG. Ionic channel organization of normal and regenerating mammalian axons. Progress in Brain Research. Vol. 71. 1987.
- Black, J.A., Kocsis, J.D., Waxman, S.G., 1990. Ion channel organization of the myelinated fiber. Trends Neurosci. 133, 48 – 54.
- Marco Mumenthaler, Manfred Stöhr, Hermann Müler-Vahl. Nobel Tıp Yayınları, Çeviri. Periferik Sinir Lezyonları ve Radiküler Sendromlar. 2005: 1-95.
- Bilimsel ve Teknik Yayınları Vakfı. Periferik Nöropati. 1995: 17-36.
- Gordon TR, Kocsis JD and Waxman SG. TEA-sensitive Potassium channels and inward rectification in regenerated rat sciatic nerve. Muscle and nerve, 1991; 14: 640-646.
- Eng DL, Gordon TR, Kocsis JD and Waxman SG. Current clamp analysis of time-dependent rectification in rat optic nerve. J. Physiol, 1990; 421: 185-202
- J. P. Ballantyne and M. J. Campbell. Electrophysiological study after surgical repair of sectioned human peripheral nerves. Journal of Neurology, Neurosurgery, and Psychiatry, 1973, 36, 797-805
- Stampfli R.: A new method for measuring potentials with external electrodes. Experienta, 1954;10:508-509.
Öz
Amaç: Bu çalışmada seçici olarak sistemik ve yerleşik makrofaj populasyonunu baskılayan bir ajan olan lipozom ile kaplanmış Klodronatın (LEC: Liposome Encapsulated Clodronate) periferik sinir hasarı sonrası dejenerasyon-rejenerasyon sürecine etkisinin araştırılması amaçlandı.
Gereç ve Yöntem: Deneylerimizde 8 haftalık wistar türü erkek sıçanlar rastgele olarak 5 gruba ayrıldı. A grubu kontrol grubu olarak seçildi. B4 ve B8 grupları ezilme grubu olup sağ siyatik sinirleri hasarlandı. C4 ve C8 grupları ise ezilme + LEC uygulanan gruplar olarak seçildi. Hasarlanma sonrası C gruplarına 5. 10. ve 15. günlerde intravenöz LEC uygulandı. Hasarlanmayı takiben 4 ve 8 hafta sonra B ve C gruplarının siyatik sinirlerinden önce EMG kaydı alındı sonra sinirler disekte edildi. Bu demetlerden, 4-Aminopiridin (4-Ap) uygulaması öncesi ve sonrasında bir in-vitro elektrofizyolojik yöntem olan Sukroz-gap tekniği ile Bileşik Sinir Aksiyon Potansiyelleri (BSAP) kayıtlandı.
Bulgular: B ve C gruplarında iletim hızları ile BSAP genliği, yükselme süresi (DT), yarı düşme süresi (½ FT) ve latans parametreleri üzerine LEC’in anlamlı bir etkisi görülmedi (p>0.05). Ancak 4-Ap uygulandıktan sonra oluşan bir fenomen olan gecikmiş depolarizasyon (del-dep) genliği üzerinde LEC’in anlamlı etkisi görüldü (p<0.05).
Sonuç: Elde ettiğimiz bulgular ışığında LEC’in yaralanma sonrası ortaya çıkan Wallerian dejenerasyon sürecini kısalttığı ve rejeneratif bir etki olarakta miyelinizasyonu hızlandırdığını söylenebilir.
Anahtar Kelimeler: Periferik Sinir Hasarı, Makrofaj, Klodronate, Sukroz-gap, Aksiyon Potasiyeli
Anahtar Kelimeler
Kaynakça
- Ide C. Peripheral nerve regeneration. Neurosci Res, 25: 101-121, 1996
- Garbaya B, Heapec A.M, Sargueila F, Cassagnea C.Myelin synthesis in the peripheral nervous system. Prog Neurobiol 61: 267-304, 2000.
- Bruck W. The role of macrophages in Wallerian degeneration. Brain Path, 7: 741-752,1997
- Perry VH, Brown MC. Role of macrophages in peripheral nerve degeneration and repair. Bioassays, 14: 401-406, 1992
- Van Rooijen N, van Kesteren-Hendrikx. "In vivo" depletion of macrophages by liposome-mediated "suicide".Methods Enzymol. 2003;373:3-16.
- Van Rooijen N., Sanders A., Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications, J. Immunol. Methods, 174, 83-93, (1994).
- Mustafa GÜVEN, İbrahim KAHRAMAN, Filiz KOÇ, Hacer BOZDEMİR, Yakup SARICA, İsmail GÜNAY. The Effects of Oxcarbazepine on 4-Aminopyridine-Induced Afterpotentials on Isolated Rat Sural Nerves. Journal of Neurological Sciences [Turk] 2010;27:(2): 139-149.
- Guven M, Kahraman I, Güneş Y, Gunay I.: Effect of Tramadol on peripheral nerves: An in-vitro electrophysiological study on the sural and tibial nerves of the rat. Journal of Medical Science (Türkiye Klinikleri). 2011;31(1).
- Waxman SG, Ritche JM: Molecular dissection of the myelinated axon. Ann Neurol 1993:33:121-136.
- Rizzo MA, Kocsis JD, Waxman SG. Slow sodium conductances of dorsal root ganglion neurons: intraneuronal homogeneity and interneuronal heterogeneity. J Neurophysiol. 1994 Dec;72(6):2796-815.
- Honmou, O., Utzschneider, D.A., Rizzo, M.A., Bowe, C.M., Waxman, S.G., Kocsis, J.D.,. Delayed depolarization and slow sodium currents in cutaneous afferents. J. Neurophysiol. 1994;71:1627–1637.
- Nonaka T, Honmou O, Sakai J, Hashi K, Kocsis JD. Excitability changes of dorsal root axons following nerve injury: implications for injury-induced changes in axonal Na+ channels. Brain Research. 2000;859:280-285.
- Kocsis JD and Waxman SG. Ionic channel organization of normal and regenerating mammalian axons. Progress in Brain Research. Vol. 71. 1987.
- Black, J.A., Kocsis, J.D., Waxman, S.G., 1990. Ion channel organization of the myelinated fiber. Trends Neurosci. 133, 48 – 54.
- Marco Mumenthaler, Manfred Stöhr, Hermann Müler-Vahl. Nobel Tıp Yayınları, Çeviri. Periferik Sinir Lezyonları ve Radiküler Sendromlar. 2005: 1-95.
- Bilimsel ve Teknik Yayınları Vakfı. Periferik Nöropati. 1995: 17-36.
- Gordon TR, Kocsis JD and Waxman SG. TEA-sensitive Potassium channels and inward rectification in regenerated rat sciatic nerve. Muscle and nerve, 1991; 14: 640-646.
- Eng DL, Gordon TR, Kocsis JD and Waxman SG. Current clamp analysis of time-dependent rectification in rat optic nerve. J. Physiol, 1990; 421: 185-202
- J. P. Ballantyne and M. J. Campbell. Electrophysiological study after surgical repair of sectioned human peripheral nerves. Journal of Neurology, Neurosurgery, and Psychiatry, 1973, 36, 797-805
- Stampfli R.: A new method for measuring potentials with external electrodes. Experienta, 1954;10:508-509.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Bölüm | Original Articles |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Mart 2015 |
| Gönderilme Tarihi | 8 Nisan 2015 |
| Yayımlandığı Sayı | Yıl 2015 Cilt: 6 Sayı: 21 |
