Serum markers of neuroinflammation and oxidative stress in modeling spinal injury of various genesis
https://doi.org/10.47093/2218-7332.2024.15.1.36-46
Abstract
Aim. To evaluate changes in the concentration of molecules that mark the neurodegenerative process, experimental spinal cord injuries (SCI) of various origins were studied.
Materials and methods. SCI was modeled in six-month-old male Wistar rats by exposing the T10 vertebra to: carbon dioxide under a pressure of 2 N/cm2 (pneumocontusion); free-falling load of three weights of 1.12 N/cm2, 1.68 N/cm2, 1.96 N/cm2 (contusion injury); compression with forceps (compression injury); partial hemisection of the spinal cord; mechanical laminectomy using a mechanical drill. There were 6 rats in each group, including the intact control group. On the 28th day after a single application of SCI in rats, the concentrations of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), albumin, thiobarbituric acid reactive substances (TBA-RS) and superoxide dismutase activity were assessed in the blood serum.
Results. When modeling SCI of various origins in rats, the serum concentration of TNF-α increased (from 115.5% (p < 0.05) in mild contusion to 234.5% (p < 0.05) in compression trauma compared to intact control) as well as IL-6 (from 49.2% (p < 0.05) in mechanical laminectomy to 89.8% (p < 0.05) in hemisection compared with intact control), suggesting activation of inflammatory reactions. The concentration of albumin in the blood serum of rats with SCI was lower than that of intact animals, especially in the hemisection group – by 41.9% (p < 0.05). Animals with SCI had an increase in TBA-RS concentration ranging from 103.2% (p < 0.05) in mild contusion and compression to 135.5% (p < 0.05) in pneumocontusion, and a decrease in superoxide dismutase activity ranging from 26.3% (p < 0.05) in laminectomy to 31.7% (p < 0.05) in hemisection. At the same time, injuries caused by spinal compression and hemisection led to a more pronounced activation of the inflammatory process, as evidenced by the increased TNF-α content compared to other variants of SCI modeling.
Conclusion. All SCI simulations resulted in equivalent activation of oxidative stress, while inflammation is more pronounced when reproducing compression injury and injury caused by spinal hemisection.
About the Authors
D. I. PozdnyakovRussian Federation
Dmitry I. Pozdnyakov – Cand. of Sci. (Pharm.), Associate Professor, Head of the Department of Pharmacology with the course of Clinical Pharmacology; Leading Researcher
Kalinin Ave., 11, Pyatigorsk, 357532
Kirov Ave., 30, Pyatigorsk, 357501
V. V. Kozlova
Russian Federation
Viktoriya V. Kozlova – Cand. of Sci. (Pharm.), Associate Professor, Department of Pharmacology with the course of Clinical Pharmacology; Head of the experimental laboratory with vivarium
Kalinin Ave., 11, Pyatigorsk, 357532
Kirov Ave., 30, Pyatigorsk, 357501
V. F. Reps
Russian Federation
Valentina F. Reps – Dr. of Sci. (Biol.), Professor, Department of Therapy; Leading Researcher
Kalinin Ave., 11, Pyatigorsk, 357532
Kirov Ave., 30, Pyatigorsk, 357501
References
1. Eli I., Lerner D.P., Ghogawala Z. Acute traumatic spinal cord injury. Neurol Clin. 2021 May; 39(2): 471–488. https://doi.org/10.1016/j.ncl.2021.02.004. Epub 2021 Mar 31. PMID: 33896529
2. Leemhuis E., Favieri F., Forte G., Pazzaglia M. Integrated neuroregenerative techniques for plasticity of the injured spinal cord. Biomedicines. 2022 Oct 13; 10(10): 2563. https://doi.org/10.3390/biomedicines10102563. PMID: 36289825; PMCID: PMC9599452
3. Ding W., Hu S., Wang P., et al. Spinal cord injury: the global incidence, prevalence, and disability from the Global Burden of Disease study 2019. Spine (Phila Pa 1976). 2022 Nov 1; 47(21): 1532–1540. https://doi.org/10.1097/BRS.0000000000004417. Epub 2022 Jun 30. PMID: 35857624
4. Garifulin R.R., Izmailov A.A., Markosyan V.A., et al. Features of neuroglia at the epicenter of spinal cord contusion injury and at distant areas in mini-pigs. Sechenov Medical Journal. 2023; 14(3): 19–27 (In Russian). https://doi.org/10.47093/2218-7332.2023.14.3.19-27
5. Elliott C.S., Dallas K.B., Zlatev D., et al. Volitional voiding of the bladder after spinal cord injury: validation of bilateral lower extremity motor function as a key predictor. J Urol. 2018 Jul; 200(1): 154–160. https://doi.org/10.1016/j.juro.2018.02.064. Epub 2018 Feb 17. PMID: 29458066.
6. Ramalho B.D.S., de Almeida F.M., Martinez A.M.B. Cell therapy and delivery strategies for spinal cord injury. Histol Histopathol. 2021 Sep; 36(9): 907–920. https://doi.org/10.14670/HH-18-350. Epub 2021 Jun 10. PMID: 34109994
7. Liu Y., Liu J., Liu B. Identifi cation of Circular RNA expression profi les and their implication in spinal cord injury rats at the immediate phase. J Mol Neurosci. 2020 Nov; 70(11): 1894–1905. https://doi.org/10.1007/s12031-020-01586-9. Epub 2020 Jun 10. PMID: 32524420
8. Alizadeh A., Dyck S.M., Karimi-Abdolrezaee S. Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms. Front Neurol. 2019 Mar 22; 10: 282. https://doi.org/10.3389/fneur.2019.00282. PMID: 30967837; PMCID: PMC6439316
9. Huang Z., Wang J., Li C., et al. Application of natural antioxidants from traditional Chinese medicine in the treatment of spinal cord injury. Front Pharmacol. 2022 Oct 5; 13: 976757. https://doi.org/10.3389/fphar.2022.976757. PMID: 36278149; PMCID: PMC9579378
10. Sabirov D., Ogurcov S., Shulman I., et al. Comparative analysis of cytokine profi les in cerebrospinal fl uid and blood serum in patients with acute and subacute spinal cord injury. Biomedicines. 2023 Sep 26; 11(10): 2641. https://doi.org/10.3390/biomedicines11102641. PMID: 37893015; PMCID: PMC10604120
11. Sabirov D., Ogurcov S., Baichurina I., et al. Molecular diagnostics in neurotrauma: Are there reliable biomarkers and effective methods for their detection? Front Mol Biosci. 2022 Sep 29; 9: 1017916. https://doi.org/10.3389/fmolb.2022.1017916. PMID: 36250009; PMCID: PMC9557129
12. Anjum A., Yazid M.D., Fauzi Daud M., et al. Spinal cord injury: pathophysiology, multimolecular interactions, and underlying recovery mechanisms. Int J Mol Sci. 2020 Oct 13; 21(20): 7533. https://doi.org/10.3390/ijms21207533. PMID: 33066029; PMCID: PMC7589539
13. Tong B., Jutzeler C.R., Cragg J.J., et al. Serum albumin predicts long-term neurological outcomes after acute spinal cord injury. Neurorehabil Neural Repair. 2018 Jan; 32(1): 7–17. https://doi.org/10.1177/1545968317746781. Epub 2017 Dec 24. PMID: 29276840
14. Sheinenzon A., Shehadeh M., Michelis R., et al. Serum albumin levels and infl ammation. Int J Biol Macromol. 2021 Aug 1; 184: 857–862. https://doi.org/10.1016/j.ijbiomac.2021.06.140. Epub 2021 Jun 25. PMID: 34181998
15. Jha R.M., Kochanek P.M., Simard J.M. Pat hoph ysiology and treatment of cerebral edema in traumatic brain injury. Neuropharmacology. 2019 Feb; 145 (Pt B): 230–246. https://doi.org/10.1016/j.neuropharm.2018.08.004. Epub 2018 Aug 4. PMID: 30086289; PMCID: PMC6309515
16. Zhang C., Zhai T., Zhu J., et al. Research progress of antioxidants in oxidative stress therapy after spinal cord injury. Neurochem Res. 2023 Dec; 48(12): 3473–3484. https://doi.org/10.1007/s11064-023-03993-x. Epub 2023 Aug 1. PMID: 37526867
17. Frantsuzov R., Mondal S., Walsh C.M., et al. A fi nite element model of contusion spinal cord injury in rodents. J Mech Behav Biomed Mater. 2023 Jun; 142: 105856. https://doi.org/10.1016/j.jmbbm.2023.105856. Epub 2023 Apr 17. PMID: 37087955
18. Csomó K.B., Varga G., Belik A.A., et al. A minimally invasive, fast spinal cord lateral hemisection technique for modeling open spinal cord injuries in rats. J Vis Exp. 2022 Mar 23; (181). https://doi.org/10.3791/63534. PMID: 35404342
19. Marcol W., Slusarczyk W., Gzik M., et al. Air gun impactor−a novel model of graded white matter spinal cord injury in rodents. J. Reconstr. Microsurg. 2012 Oct; 28(8): 561–568. https://doi.org/10.1055/s-0032-1315779. Epub 2012 Jun 18. PMID: 22711195
20. Harikrishnan V.S., Krishnan L.K., Abelson K.S.P. A novel technique to develop thoracic spinal laminectomy and a methodology to assess the functionality and welfare of the contusion spinal cord injury (SCI) rat model. PLoS One. 2019 Jul 2; 14(7): e0219001. https://doi.org/10.1371/journal.pone.0219001. PMID: 31265469; PMCID: PMC6605676
21. Shen Y., Wang Y.P., Cheng X., et al. Autophagy regulation combined with stem cell therapy for treatment of spinal cord injury. Neural Regen Res. 2023 Aug; 18(8): 1629–1636. https://doi.org/10.4103/1673-5374.363189. PMID: 36751772; PMCID: PMC10154487
22. Kigerl K.A., Gensel J.C., Ankeny D.P., et al. Identifi cation of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009 Oct 28; 29(43): 13435–13444. https://doi.org/10.1523/JNEUROSCI.3257-09.2009. PMID: 19864556; PMCID: PMC2788152
23. Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges. Anal Biochem. 2017 May 1; 524: 13– 30. https://doi.org/10.1016/j.ab.2016.10.021. Epub 2016 Oct 24. PMID: 27789233
24. Kielkopf C.L., Bauer W., Urbatsch I.L. Bradford assay for determining protein concentration. Cold Spring Harb Protoc. 2020 Apr 1; 2020(4): 102269. https://doi.org/10.1101/pdb.prot102269. PMID: 32238597
25. Gumral N., Aslankoc R., Senol N., Cankara F.N. Protective effect of alpha-lipoic acid against liver damage induced by cigarette smoke: an in vivo study. Saudi J Med Med Sci. 2021 May-Aug; 9(2): 145–151. https://doi.org/10.4103/sjmms.sjmms_387_20. Epub 2021 Apr 29. PMID: 34084105; PMCID: PMC8152379
26. Doblado L.R., Martínez-Ramos C., Pradas M.M. Multimodular bio-inspired organized structures guiding long-distance axonal regeneration. Biomedicines. 2022 Sep 8; 10(9): 2228. https://doi.org/10.3390/biomedicines10092228. PMID: 36140328; PMCID: PMC9496454
27. Sun S., Li J., Wang S., et al. CHIT1-positive microglia drive motor neuron ageing in the primate spinal cord. Nature. 2023 Dec; 624(7992): 611–620. https://doi.org/10.1038/s41586-023-067831. Epub 2023 Oct 31. PMID: 37907096
28. Hu X., Xu W., Ren Y., et al. Spinal cord injury: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 2023 Jun 26; 8(1): 245. Published 2023 Jun 26. https://doi.org/10.1038/s41392-023-01477-6. PMID: 37357239; PMCID: PMC10291001
29. Kayabaş M., Şahin L., Makav M., et al. Protective effect of hydrogen-rich saline on spinal cord damage in rats. Pharmaceuticals (Basel). 2023 Apr 1; 16(4): 527. https://doi.org/10.3390/ph16040527. PMID: 37111284; PMCID: PMC10143771
30. Kung W.M., Chang C.J., Chen T.Y., Lin M.S. Cryogen spray cooling mitigates infl ammation and injury-induced CISD2 decline in rat spinal cord hemisection model. J Integr Neurosci. 2020 Dec 30; 19(4): 619–628. https://doi.org/10.31083/j.jin.2020.04.255. PMID: 33378836
31. Yu M., Wang Z., Wang D., et al. Oxidative stress following spinal cord injury: From molecular mechanisms to therapeutic targets. J Neurosci Res. 2023 Oct; 101(10): 1538–1554. https://doi.org/10.1002/jnr.25221. Epub 2023 Jun 5. PMID:
Supplementary files
|
1. Graphic abstract | |
Subject | ||
Type | Исследовательские инструменты | |
View
(255KB)
|
Indexing metadata ▾ |
![]() |
2. ARRIVE author checklist | |
Subject | ||
Type | Исследовательские инструменты | |
Download
(108KB)
|
Indexing metadata ▾ |