Serum level of αII-spectrin breakdown products (SBDPs) as a potential marker of brain ischemia-reperfusion injury after carotid endarterectomy
Abstract
Introduction: Stroke remains one of the main causes of morbidity and mortality worldwide. Carotid endarterectomy (CEA) reduces the incidence of ischemic stroke or death in patients with symptomatic carotid artery stenosis more effectively than pharmacological therapy alone. SBDPs (spectrin breakdown products): SBDP 120, SBDP145, and SBDP150 are the product of proteolysis of αII-spectrin (280 kDa) — an important structural component of the neuronal cytoskeleton, particularly present in axons. Increased serum level of SBDPs was previously observed in traumatic brain injury, subarachnoid hemorrhage (SAH), or brain ischemia.
Material and methods: The aim of our study was to investigate changes in serum levels of SBDP120 and SBDP145 in patients undergoing uncomplicated CEA. The study included 22 patients with severe carotid artery stenosis, qualified for CEA. Blood samples were taken from the antecubital vein at three different intervals (24 h before CEA, 12 and 48 h after surgery). SBDP’s serum levels were measured by a commercially available enzyme-linked immunosorbent assay (ELISA).
Results: The study showed that serum SBDP120 levels were significantly decreased 48 h after CEA when compared to the level before the surgery. SBDP145 levels were significantly decreased 12h after the procedure and then remained at a similar level 48h after CEA.
Conclusions: In patients with high-grade carotid artery stenosis SBDP120 and SBDP145 serum level decreases after an uncomplicated CEA, therefore alterations from this curve may be a marker of neurological complications after the procedure. Higher SBDP levels before the procedure may represent brain damage caused by chronic ischemia.
Keywords: carotid endarterectomycarotid artery stenosisstrokeαII-spectrin breakdown products
References
- Favate AS, Younger DS. Epidemiology of Ischemic Stroke. Neurol Clin. 2016; 34(4): 967–980.
- The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. WHO MONICA Project Principal Investigators. J Clin Epidemiol. 1988; 41(2): 105–114.
- Deb P, Sharma S, Hassan KM. Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology. 2010; 17(3): 197–218.
- Yip HK, Sung PH, Wu CJ, et al. Carotid stenting and endarterectomy. Int J Cardiol. 2016; 214: 166–174.
- Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). The Lancet. 1998; 351(9113): 1379–1387.
- Mayberg MR. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Veterans Affairs Cooperative Studies Program 309 Trialist Group. JAMA: The Journal of the American Medical Association. 1991; 266(23): 3289–3294.
- Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med. 1998; 339(20): 1415–1425.
- Ferguson GG, Eliasziw M, Barr HW, et al. The North American Symptomatic Carotid Endarterectomy Trial : surgical results in 1415 patients. Stroke. 1999; 30(9): 1751–1758.
- Gupta N, Corriere MA, Dodson TF, et al. The incidence of microemboli to the brain is less with endarterectomy than with percutaneous revascularization with distal filters or flow reversal. J Vasc Surg. 2011; 53(2): 316–322.
- Backhaus R, Boy S, Fuchs K, et al. Hyperperfusion syndrome after MCA embolectomy - a rare complication? Am J Case Rep. 2013; 14: 513–517.
- Lieb M, Shah U, Hines G. Cerebral Hyperperfusion Syndrome After Carotid Intervention. Cardiology in Review. 2012; 20(2): 84–89.
- Capoccia L, Sbarigia E, Rizzo A, et al. Contralateral Occlusion Increases the Risk of Neurological Complications Associated with Carotid Endarterectomy. Int J Vasc Med. 2015; 2015: 1–8.
- Dash PK, Zhao J, Hergenroeder G, et al. Biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy for traumatic brain injury. Neurotherapeutics. 2010; 7(1): 100–114.
- Zhang Z, Larner SF, Liu MC, et al. Multiple alphaII-spectrin breakdown products distinguish calpain and caspase dominated necrotic and apoptotic cell death pathways. Apoptosis. 2009; 14(11): 1289–1298.
- Glushakova OY, Glushakov AV, Miller ER, et al. Biomarkers for acute diagnosis and management of stroke in neurointensive care units. Brain Circ. 2016; 2(1): 28–47.
- Pineda JA, Lewis SB, Valadka AB, et al. Clinical significance of alphaII-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury. J Neurotrauma. 2007; 24(2): 354–366.
- Siman R, Toraskar N, Dang A, et al. A panel of neuron-enriched proteins as markers for traumatic brain injury in humans. J Neurotrauma. 2009; 26(11): 1867–1877.
- Brophy GM, Pineda JA, Papa L, et al. alphaII-Spectrin breakdown product cerebrospinal fluid exposure metrics suggest differences in cellular injury mechanisms after severe traumatic brain injury. J Neurotrauma. 2009; 26(4): 471–479.
- Czeiter E, Mondello S, Kovacs N, et al. Brain injury biomarkers may improve the predictive power of the IMPACT outcome calculator. J Neurotrauma. 2012; 29(9): 1770–1778.
- Papa L, Robertson CS, Wang KKW, et al. Biomarkers improve clinical outcome predictors of mortality following non-penetrating severe traumatic brain injury. Neurocrit Care. 2015; 22(1): 52–64.
- Lad SP, Hegen H, Gupta G, et al. Proteomic biomarker discovery in cerebrospinal fluid for cerebral vasospasm following subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 2012; 21(1): 30–41.
- Lewis SB, Velat GJ, Miralia L, et al. Alpha-II spectrin breakdown products in aneurysmal subarachnoid hemorrhage: a novel biomarker of proteolytic injury. J Neurosurg. 2007; 107(4): 792–796.
- Siman R, Giovannone N, Toraskar N, et al. Evidence that a panel of neurodegeneration biomarkers predicts vasospasm, infarction, and outcome in aneurysmal subarachnoid hemorrhage. PLoS One. 2011; 6(12): e28938.
- Papa L, Rosenthal K, Silvestri F, et al. Evaluation of alpha-II-spectrin breakdown products as potential biomarkers for early recognition and severity of aneurysmal subarachnoid hemorrhage. Sci Rep. 2018; 8(1): 13308.
- Ren C, Zoltewicz S, Guingab-Cagmat J, et al. Different expression of ubiquitin C-terminal hydrolase-L1 and αII-spectrin in ischemic and hemorrhagic stroke: Potential biomarkers in diagnosis. Brain Res. 2013; 1540: 84–91.
- Pike BR, Flint J, Dave JR, et al. Accumulation of calpain and caspase-3 proteolytic fragments of brain-derived alphaII-spectrin in cerebral spinal fluid after middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab. 2004; 24(1): 98–106.
- Ringger NC, O'Steen BE, Brabham JG, et al. A novel marker for traumatic brain injury: CSF alphaII-spectrin breakdown product levels. J Neurotrauma. 2004; 21(10): 1443–1456.
- Farkas O, Polgár B, Szekeres-Barthó J, et al. Spectrin breakdown products in the cerebrospinal fluid in severe head injury--preliminary observations. Acta Neurochir (Wien). 2005; 147(8): 855–861.
- Cardali S, Maugeri R. Detection of alphaII-spectrin and breakdown products in humans after severe traumatic brain injury. J Neurosurg Sci. 2006 Jun;50(2):25-31. .
- Pineda JA, Lewis SB, Valadka AB, et al. Clinical significance of alphaII-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury. J Neurotrauma. 2007; 24(2): 354–366.
- Mondello S, Robicsek SA, Gabrielli A, et al. αII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J Neurotrauma. 2010; 27(7): 1203–1213.
- Chen S, Shi Q, Zheng S, et al. Role of α-II-spectrin breakdown products in the prediction of the severity and clinical outcome of acute traumatic brain injury. Exp Ther Med. 2016; 11(5): 2049–2053.
- Frankel M, Fan L, Yeatts SD, et al. Association of Very Early Serum Levels of S100B, Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and Spectrin Breakdown Product with Outcome in ProTECT III. J Neurotrauma. 2019; 36(20): 2863–2871.
- Berger RP, Hayes RL, Richichi R, et al. Serum concentrations of ubiquitin C-terminal hydrolase-L1 and αII-spectrin breakdown product 145 kDa correlate with outcome after pediatric TBI. J Neurotrauma. 2012; 29(1): 162–167.
- Liu Y, Yao X, Lv X, et al. The role of spectrin breakdown products in patients with traumatic brain injury: a systematic review and meta-analysis. Neurol Sci. 2023; 44(4): 1171–1183.
- Lewis SB, Velat GJ, Miralia L, et al. Alpha-II spectrin breakdown products in aneurysmal subarachnoid hemorrhage: a novel biomarker of proteolytic injury. J Neurosurg. 2007; 107(4): 792–796.
- Zhang C, Siman R, Xu YA, et al. Comparison of calpain and caspase activities in the adult rat brain after transient forebrain ischemia. Neurobiol Dis. 2002; 10(3): 289–205.
- Connolly ES, Winfree CJ, Rampersad A, et al. Serum S100B protein levels are correlated with subclinical neurocognitive declines after carotid endarterectomy. Neurosurgery. 2001; 49(5): 1076–82; discussion 1082.
- Brightwell RE, Sherwood RA, Athanasiou T, et al. The neurological morbidity of carotid revascularisation: using markers of cellular brain injury to compare CEA and CAS. Eur J Vasc Endovasc Surg. 2007; 34(5): 552–560.
- Rasmussen LS, Christiansen M, Johnsen J, et al. Subtle brain damage cannot be detected by measuring neuron-specific enolase and S-100beta protein after carotid endarterectomy. J Cardiothorac Vasc Anesth. 2000; 14(2): 166–170.
- Mussack T, Hauser C, Klauss V, et al. Serum S-100B protein levels during and after successful carotid artery stenting or carotid endarterectomy. J Endovasc Ther. 2006; 13(1): 39–46.
- Terlecki P, Pawlik P, Iwaniuk A, et al. Carotid surgery affects plasma kynurenic acid concentration: a pilot study. Med Sci Monit. 2014; 20: 303–310.
- Ilzecki M, Ilzecka J, Przywara S, et al. Serum Carnosine Dipeptidase 1 and Ubiquitin C - Terminal Hydrolase L1 as Markers of Brain Damage in Patients After Carotid Endarterectomy. Ulutas Med J. 2016; 2(3): 132.
- Ilzecki M, Przywara S, Ilzecka J, et al. Serum microtubule associated protein tau and myelin basic protein as the potential markers of brain ischaemia-reperfusion injury in patients undergoing carotid endarterectomy. Acta Angiologica. 2016; 22(2): 37–43.
- Iłżecki M, Iłżecka J, Przywara S, et al. Effect of carotid endarterectomy on brain damage markers. Acta Neurol Scand. 2017; 135(3): 352–359.
- Ilzecki M, Przywara S, Ilzecka J, et al. Serum glial fibrillary acidic protein as a marker of brain damage in patients after carotid endarterectomy. Acta Angiologica. 2016; 22(1): 1–4.
- Iłżecki M, Iłżecka J, Przywara S, et al. Serum Neuron-Specific Enolase as a Marker of Brain Ischemia-Reperfusion Injury in Patients Undergoing Carotid Endarterectomy. Acta Clin Croat. 2016; 55(4): 579–584.