Abstract
Introduction. Additionally to electrophysiological and clinical methods the neurofilament light chains (Nf-L) concentration in blood plasma is considered as a marker for predicting functional outcomes.
The aim of the study. Assessment of neurofilament light chains (Nf-L) level in plasma in 21 days after experimental stroke.
Methods. A randomized controlled trial was conducted on mature male rats of the SHR lines (n = 20) and WKY (n = 20) weighing 250 ± 50 g. Cerebral ischemia was performed by monofilament occlusion of the left middle cerebral artery under anesthesia (Zoletil +Xylazine) at a dose of 0,88 ml/kg.
Results. On Day 1 post- MCA occlusion, WKY animals had a Garcia score 6 and SHR rats had a score 5 out of 18. WKY testing data on days 3, 5, and 7 revealed decreased muscle strength (MCAo: 2.0 ± 0.1 N; Sham: 3.0 ± 0.2N; p < 0.05). SHR testing data on on days 3, 5 revealed a decrease (MCAo: 1.9 ± 0.2N; Sham: 3.0 ± 0.2N, p < 0.05). At the same postoperative time, the Nf-L concentration in SHR animals was 2.7-fold higher compared to controls and different from WKY animals.
Conclusion. The change in Nf-L concentration in rats after SHR stroke is more pronounced than in WKY rats. A change in the concentration of Nf-L in blood plasma indicates the predominant course of destructive processes in the nervous tissue. Stroke in SHR rats is accompanied by a more pronounced and prolonged decrease in muscle strength and impaired coordination.
Authors and affiliations
M.E. Kolpakova(1), А.А. Yakovleva(2)
1-Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova Emb., 6, St-Petersburg, 199034, Russian Federation;
2-First Pavlov State Medical University, L. Tolstoy str., 6–8, St-Petersburg, 197022, Russian Federation
References
Cipolla M.J., Liebeskind D.S., Chan S.-L. The importance of comorbidities in ischemic stroke: impact of hypertension on the cerebral circulation. J. Cereb. Blood Flow Metab. 2018; 38 (12): 2129–49. DOI: 10,1177/ 0271678X18800589
Liu M.C., Akinyi L., Scharf D., Mo J., Larner S.F., Muller U., Oli M.W., Zheng W., Kobeissy F., Papa L., Lu X.C., Dave J.R., Tortella F.C., Hayes R.L., Wang K.K. Ubiquitin C-terminal hydrolase-L1 as a biomarker for ischemic and traumatic brain injury in rats. Eur. J. Neurosci. 2010; 31 (4): 722–32. DOI: 10,1111/j.1460-9568.2010,07097
Weiss-Sadan T., Gotsman I., Blum G. Cysteine proteases in atherosclerosis. FEBS J. 2017; 284 (10): 1455–72. DOI: 10,1111/febs.14043
Khalil M., Teunissen C.E., Otto M., Piehl F., Sormani M.P., Gattringer T., Barro C., Kappos L., Comabella M., Fazekas F., Petzold A., Blennow K., Zetterberg H., Kuhle J. Neurofilaments as biomarkers in neurological disorders. Nat. Rev. Neurol. 2018; 14 (10): 577–89. DOI: 10,1038/s41582-018-0058-z.
Perrot R., Berges R., Bocquet A., Eyer J. Review of the multiple aspects of neurofilament functions, and their possible contribution to neurodegeneration. Mol. Neurobiol. 2008; 38 (1): 27–65. DOI: 10,1007/s12035-008-8033-0,
Weissman J.D., Khunteev G.A., Heath R., Dambinova S.A. NR2 antibodies: risk assessment of transient ischemic attack (TIA)/ stroke in patients with history of isolated and multiple cerebrovascular events. J. Neurol. Sci. 2011; 300: 97–102. DOI: 10,1016/j.jns.2010,09,023.
Ueno Y., Chopp M., Zhang L., Buller B., Liu Z., Lehman N.L., Liu X.S., Zhang Y., Roberts C., Zhang Z.G. Axonal outgrowth and dendritic plasticity in the cortical peri-infarct area after experimental stroke. Stroke 2012; 43 (8): 2221–8. DOI: 10,1161/ STROKEAHA.111.646224
. Maas M.B. Furie K.L. Molecular biomarkers in stroke diagnosis and prognosis. Biomark. Med. 2009; 3 (4): 363–83. DOI: 10,2217/bmm,09.30,
Perrot R., Eyer J. Neuronal intermediate filaments and neurodegenerative disorders. Brain Res. Bull. 2009; 80 (4–5): 282–95. DOI: 10,1016/j.brainresbull.2009,06,004.
. Petzold A., Keir G., Green A.J., Giovannoni G., Thompson E.J. A specific ELISA for measuring neurofilament heavy chain phosphoforms. J. Immunol. Methods 2003; 278: 179–90, DOI: 10,1016/s0022-1759(03)00189-3
Langhorne P., Bernhardt J., Kwakkel G. Stroke rehabilitation. Lancet 2011; 377 (9778): 1693–702. DOI: 10,1016/S0140-6736(11)60325-5
. Hara Y. Brain plasticity and rehabilitation in stroke patients. J. Nippon Med. Sch. 2015; 82 (1): 4–13. DOI: 10,1272/jnms.82.4.
. Meeker K.L., Luckett P.H., Barthélemy N.R., Hobbs D.A., Chen C., Bollinger J., Ovod V., Shaney F. et al. Comparison of cerebrospinal fluid, plasma and neuroimaging biomarker utility in Alzheimer’s disease Brain communication. 2024; 1–15. DOI: 10,1093/braincomms/fcae081
. Kunze A., Zierath D., Drogomiretskiy O., Becker K. Strain differences in fatigue and depression after experimental stroke. Translational Stroke Research 2014; 5 (5): 604–11. DOI: 10,1007/s12975-014-0350-1
. Yuan A.; nixon R. A. Neurofilament proteins as biomarkers to monitor neurological disease and the efficacy of therapies. Front. Neurosci. 2021; 15: 1–28. DOI: 10,3389/fnins.2021.689938
. Song M., Woodbury A., Yu S.P. White matter injury and potential treatment in ischemic stroke. In: Baltan S, Carmichael ST, Matute C, Xi G, Zhang JH (eds) White matter injury in stroke and CNS disease. Springer; new York; nY, 2014; 39–52. DOI: 10,1007/978-1-4614-9123-1_2
. Härtig W., Krueger M., Hofmann S., Preißler H., Märkel M., Frydrychowicz C., Mueller W.C., Bechmann I., Michalski D. Up-regulation of neurofilament light chains is associated with diminished immunoreactivities for MAP2 and tau after ischemic stroke in rodents and in a human case. J. Chem Neuroanat. 2016; 78: 140–8. DOI: 10,1016/j. jchemneu.2016,09,004
. Coppens S., Lehmann S., Hopley C., Hirtz C. Neurofilament-Light, a Promising Biomarker: Analytical, metrological and clinical challenges Int. J. Mol. Sci. 2023; 24 (14): 11624. DOI:10,3390/ijms241411624
Sommer C.J. Ischemic stroke: experimental models and reality. Acta Neuropathol. 2017; 133 (2): 245–61. DOI: 10,1007/ s00401-017-1667-0
. Sabayan B., Westendorp R. Neurovascular-glymphatic dysfunction and white matter lesions GeroScience 2021; 43: 1635–42. DOI: 10,1007/s11357-021-00361-x.
Kolpakova M.E., Yakovleva A.A., Polyakova L.S. The influence of remote ischemic conditioning on focal brain ischemia in rats. JBBS 2021; 11 (6): DOI: 10,4236/jbbs.2021.116010
. Kornhuber J., Alcolea D., Thibaut F., Gordon B.; Trojanowski J.Q., Thompson A., Handels R. et al. Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: an update of the consensus of the task force on biological markers in psychiatry of the world federation of societies of biological psychiatry World J. Biol. Psychiatry. 2018; 19 (4): 244–328. DOI: 10,1080/15622975.2017.1375556.
. Heiskanen M., Jääskeläinen O., Manninen E., Das Gupt S., Andrade P., Ciszek R., Gröhn O. et al. Plasma neurofilament light chain (NF-L) is a prognostic biomarker for cortical damage evolution but not for cognitive impairment or epileptogenesis following experimental TBI Int J Mol Sci. 2022; 23 (23): 15208. DOI: 10,3390/ijms232315208
. Salmina A.B., Kharitonova E.V., Gorina Y.V., Teplyashina E.A., Malinovskaya N.A., Khilazheva E.D. et al. Blood–brain barrier and neurovascular unit in vitro models for studying mitochondria-driven molecular mechanisms of neurodegeneration. Int. J. Mol. Sci; 2021; 22: 4661. DOI:10,3390/ijms22094661