Investigating the Activity of Alpha-synuclein Protein in Determining Neuronal Damage in Rats with Experimental Head Trauma

Yıl 2021, Cilt: 47 Sayı: 3, 445 - 449, 01.12.2021

Buşra Altınkök Şentürk Halil İbrahim Çıkrıklar Vahide Aslıhan Durak Birnur Aydin Erol Armagan

https://doi.org/10.32708/uutfd.1021011

Öz

The aim of our study was to investigate the diagnostic value of alpha-synuclein level in serum samples taken from rats in a head trauma model in which mild traumatic brain injury was created experimentally to demonstrate acute traumatic brain injury. A total of 40 adult Sprague-Dawley rats were used in our study. The subjects were divided in to 5 groups; control group (n=8) and 4 separate experimental groups (n=8). The model described by Marmarou et al. was modified and applied in our study. In this model, we aimed at creating a trauma of 0,05, 0,1, 0,2 and 0,4 Newtons respectively, by releasing balls of different heights and different weights using the free fall method. The level of α-syn was investigated in blood samples taken from the heart of rats 2 hours after induction of trauma. When compared to the control group, a decrease in α-syn levels was observed in groups with trauma severity of 0,05 and 0,2 Newton. α-Syn levels in the group with more severe trauma (0,2 Newton) was found to be significantly lower than the group with least trauma (0,05 Newton). Consequently, there was no significant increase in α-syn levels in blood samples taken at the second hour from rats with different severity of head trauma. Contrarily, a decrease was observed in the two trauma groups when compared to the control group. These results suggest that α-syn levels measured from blood samples taken at the second hour after head trauma is not diagnostically effective in the early period of TBI.

Anahtar Kelimeler

HEAD TRAUMA, NEURONAL DAMAGE, ALPHA- SYNUCLEIN

Deneysel Kafa Travması Oluşturulan Sıçanlarda Nöronal Hasarı Belirlemede Alfa-sinüklein Protein Etkinliğinin Araştırılması

Öz

Çalışmamızın amacı deneysel olarak hafif travmatik beyin hasarı oluşturulan kafa travması modelinde sıçanlardan alınan serum örneklerinde alfa-sinüklein (α-syn) düzeyinin akut dönemde travmatik beyin hasarını göstermede tanısal değerini araştırmaktır. Çalışmamızda toplam 40 adet erişkin Spraque-Dawley cinsi sıçan kullanılmıştır. Denekler kontrol grubu (n=8) ve 4 ayrı deney grubu (n=8) olarak 5 gruba ayrıldılar. Çalışmamızda Marmarou ve ark.’nın tanımladığı model modifiye edilerek uygulandı. Bu modelde farklı yüksekliklerden farklı ağırlıklarda bilyeler serbest düşme yöntemiyle bırakılarak sırayla 0,05, 0,1, 0.2 ve 0,4 Newton şiddetinde travma oluşturulması hedeflendi. Travmanın indüksiyonundan 2 saat sonra sıçanların kalbinden alınan kanlarda α-syn düzeyi araştırıldı. Kontrol grubuna göre kan α-syn düzeyleri ölçüldüğünde, 0,05 ve 0,2 Newton şiddetinde travma oluşturduğumuz gruplarda düşüş görülmüştür. Daha şiddetli travma oluşturduğumuz (0,2 Newton) grup, az şiddetli oluşturduğumuz gruba (0,05 Newton) göre anlamlı olarak daha düşük bulunmuştur. Sonuç olarak farklı şiddetlerde kafa travması oluşturduğumuz sıçanlardan ikinci saatte alınan kan örneklerinden α-syn düzeylerinde anlamlı bir yükselme görülmemiştir. Aksine iki travma grubunda kontrol grubu ile kıyaslandığında düşme görülmüştür. Bu sonuçlar kafa travması sonrası ikinci saatte alınan kanlardan bakılan α-syn düzeyinin TBY için erken dönemde tanısal olarak etkin olmadığını düşündürmektedir.

Anahtar Kelimeler

kafa travması, nöronal hasar, alfa-sinüklein

Kaynakça

• 1. Yon Y, Hernández-García L, Di Giacomo G, et all violence and injury in the WHO European region. Lancet Public Health. 2020;5:e422.
• 2. Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006;21:375-8.
• 3. Clement MO. Imaging of Brain Trauma. Radiol Clin North Am. 2019;57:733-744.
• 4. Tuncer E: Klinik Radyoloji. Bursa, 1.Baskı, Güneş ve Nobel Tıp Kitabevi, 1994, BT. pp 571-706.
• 5. Bellolio MF, Bellew SD, Sangaralingham LR, et al. Access to primary care and computed tomography use in the emergency department. BMC Health Serv Res. 2018;18:154.
• 6. Dadas A, Washington J, Diaz-Arrastia R, Janigro D. Biomarkers in traumatic brain injury (TBI): a review. Neuropsychiatr Dis Treat. 2018;14:2989-3000.
• 7. Ye L, Zhang D, Shao M, et al. Lower Posttraumatic α-Synuclein Level Associated With Altered Default Mode Network Connectivity Following Acute Mild Traumatic Brain Injury. Front Neural Circuits. 2019;13:26.
• 8. Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg. 1994;80:291-300.
• 9. Kewın KW, Yang Z, Zhu T, et al. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn. 2018;18:165-180.
• 10. Manley GT, Diaz-Arrastia R, Brophy, et al. Common data elements for traumatic brain injury: recommendations from the biospecimens and biomarkers working group. Arch. Phys. Med. Rehabil. 2010;91:1667-72.
• 11. Rostami E, Davidsson J, Ng KC, et al. A Model for Mild Traumatic Brain Injury that Induces Limited Transient Memory Impairment and Increased Levels of Axon Related Serum Biomarkers. Front. Neurol. 2012;23;3:115
• 12. Anderson KJ, Scheff SW, Miller KM, et al. The phosphorylated axonal form of the neurofilament subunit NF-H (pNF-H) as a blood biomarker of traumatic brain injury. Neurotrauma. 2008;25:1079-85.
• 13. Yang SH, Gustafson J, Gangidine M,ang SH et al. A murine model of mild traumatic brain injury exhibiting cognitive and motor deficits. J. Surg. Res. 2013;184:981-8.
• 14. Li Y, Zhang L, Kallakuri S, Cohen A, Cavanaugh JM. Correlation of mechanical impact responses and biomarker levels: A new model for biomarker evaluation in TBI. J Neurol Sci. 2015;359:280-6.
• 15. Rokad D, Ghaisas S, Harischandra DS, Jin H, Anantharam V, Kanthasamy A, Kanthasamy AG. Role of neurotoxicants and traumatic brain injury in α-synuclein protein misfolding and aggregation. Brain Res Bull. 2017;133:60-70.
• 16. Newell KL, Boyer P, Gomez-Tortosa E, et al. Alphα-synuclein immunoreactivity is present in axonal swellings in neuroaxonal dystrophy and acute traumatic brain injury. J Neuropathol Exp Neurol. 1999;58:1263-8.
• 17. Irina Surgucheva, Shuangteng He, Megan C. Rich, et al. Role of synucleins in traumatic brain injury — An experimental in vitro and in vivo study in mice. Molecular and Cellular Neuroscience. 2014;63:114-23.
• 18. Acosta SA, Tajiri N, de la Pena I, et al. Alpha-synuclein as a pathological link between chronic traumatic brain injury and Parkinson's disease. J Cell Physiol. 2015;230:1024-32.
• 19. Uryu K, Chen XH, Martinez D, et al. Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans. Exp Neurol. 2007;208:185-192.
• 20. Maruichi K, Kuroda S, Chiba Y, et al. Graded model of diffuse axonal injury for studying head injury-induced cognitive dysfunction in rats. Neuropathology. 2009;29:132-9.
• 21. Mollenhauer B, Batrla R, El-Agnaf O, Galasko DR, et al. Investigating Synuclein Consortium of the Michael J. Fox Foundation for Parkinson's Research. A user's guide for α-synuclein biomarker studies in biological fluids: Perianalytical considerations. Mov Disord. 2017;32:1117-1130.
• 22. Devic I, Hwang H, Edgar JS, et al. Salivary α-synuclein and DJ-1: potential biomarkers for Parkinson's disease. Brain. 2011;134:178-9.
• 23. Mondello S, Buki A, Italiano D, Jeromin A. α-Synuclein in CSF of patients with severe traumatic brain injury. Neurology. 2013;80:1662-8.
• 24. Foulds PG, Diggle P, Mitchell JD, et al. A longitudinal study on α-synuclein in blood plasma as a biomarker for Parkinson's disease. Sci Rep. 2013;3:2540-1.
• 25. Dinh MM, Bein K, Roncal S, Byrne CM, Petchell J. Redefining the golden hour for severe head injury in an urban setting: the effect of prehospital arrival times on patient outcomes. Injury. 2013;44:606-10.
• 26. Kasa M. Kafa travması nedeni ile acil servise getirilen hastalarda serum fosforile nörofilaman ağır zincir ve nöron spesifik enolaz’ın prognostik yönden değerlendirilmesi (Uzmanlık Tezi). Konya: Necmettin Erbakan Üniversitesi 2015
• 27. Shackelford SA, Del Junco DJ, Reade MC, et al. Association of time to craniectomy with survival in patients with severe combat-related brain injury. Neurosurg Focus. 2018;45:2-3.
• 28. Carlson SW, Yan HQ, Li Y, et al. Differential Regional Responses in Soluble Monomeric Alpha Synuclein Abundance Following Traumatic Brain Injury. Mol Neurobiol. 2021;58:362-374.