Multiple Panel of Biomarkers for TIA/Stroke Evaluation
2002; Lippincott Williams & Wilkins; Volume: 33; Issue: 5 Linguagem: Inglês
10.1161/01.str.0000014922.83673.86
ISSN1524-4628
AutoresDambinova Sa, Guerman A. Khounteev, Alexandr A. Skoromets,
Tópico(s)Cerebrovascular and Carotid Artery Diseases
ResumoHomeStrokeVol. 33, No. 5Multiple Panel of Biomarkers for TIA/Stroke Evaluation Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBMultiple Panel of Biomarkers for TIA/Stroke Evaluation Svetlana A. Dambinova, PhD, DSc and Guerman A. Khounteev, MD Alexandr A. Skoromets, MD, PhD, DSc Svetlana A. DambinovaSvetlana A. Dambinova Institute of the Human Brain, Russian Academy of Sciences, St. Petersburg, Russia and Guerman A. KhounteevGuerman A. Khounteev Institute of the Human Brain, Russian Academy of Sciences, St. Petersburg, Russia Alexandr A. SkorometsAlexandr A. Skoromets Department of Neurology and Neurosurgery, I.P. Pavlov's Medical University, St. Petersburg, Russia Originally published1 May 2002https://doi.org/10.1161/01.STR.0000014922.83673.86Stroke. 2002;33:1181–1182To the Editor:Brey et al1 reported what is to their knowledge the first study to demonstrate a prospective association between sera cofactor-dependent anticardiolipin antibodies and stroke independent of other risk factors as well as myocardial infarction (MI). In addition to lending support to basic research that has shown the pathogenicity of antiphospholipid-protein antibodies (aPL) in thrombosis,2 this well-conducted epidemiological study of Japanese-American men enrolled in the Honolulu Heart Program and followed for up to 20 years provides evidence for the role of aPL as potentially important markers and/or causes of increased vascular risk associated with ischemic stroke and MI.It is known that stroke is a multisystemic disorder involving mechanisms of thrombotic and neurotoxic coupling.3 Biochemical markers including glutamate, homocysteine (a sulfinic analog of aspartate4), and N-methyl-d-aspartate (NMDA) receptor autoantibodies (aAb) are independently associated with neurotoxicity and can be measured in blood.5 The aPLs are a part of the structural components of excitatory membranes containing glutamate receptors and may be involved in the neurotoxicity process as well.3 Consequently, the appearance of elevated levels of aPL in blood represents an additional indicator of NMDA neuroreceptor damage under ischemic conditions.The development of a multiple panel of biomarkers for stroke analogous to that now in use for MI would be beneficial for the emergency bedside diagnosis of stroke and may help differentiate ischemic from hemorrhagic stroke. We assessed 3 proposed biomarkers5: glutamate and homocysteine as correlates of large and middle artery dysfunction, and NR2A aAb as a criterion of microvascular damage independently associated with neurotoxicity and thrombosis in patients with transient ischemic attack (TIA)/stroke. We studied 92 patients with high blood pressure, prestroke, and TIA, subdivided according to symptom severity, including patients with left hemispheric stroke admitted within 6 hours of stroke onset (30.4±3.2 score on the Orgogozo Stroke Scale) and patients with intracerebral hemorrhage located in the left hemisphere (Table 1). Patients underwent neurological examination and neuroimaging (computed tomography, T2-weighted MRI, diffusion-weighted imaging, and Doppler angiography).6,7 After informed consent, blood samples were collected on the day of admission from all subjects. Plasma levels of glutamate and homocysteine and serum levels of the NMDA receptor NR2A subtype were assessed by high-performance liquid chromatography and enzyme-linked immunosorbent assay.6Plasma Concentrations of Glutamate and Homocysteine and Serum Concentrations of NR2A Autoantibodies in Patients and Control SubjectsSubjectsnAge, yGenderConcentrationMFGlutamate*Homocysteine*NR2A aAb†aAb indicates autoantibodies.Data are mean±SEM, *expressed in micromoles per liter; †expressed in nanogram per milliliter; ‡P<0.05 and §P 25 cm3). When neuroprotective glycine was administered, we observed NR2A aAb reduction in patients with acute stroke that was accompanied by an improvement in neurological function.8NR2A Autoantibody Monitoring in Patients with Ischemic and Hemorrhagic StrokeTime, hNR2A Autoantibody, ng/mlIschemic Stroke*Hemorrhage*P<0.001, versus control (1.4±0.3 ng/ml).0 (on admission)5.04±0.911.72±0.1234.96±0.321.68±0.2165.10±0.711.70±0.1397.90±1.231.71±0.09127.30±1.531.64±0.20243.20±0.621.65±0.15723.50±0.501.70±0.14Our experimental9 and clinical research data have demonstrated that simultaneous assessment of these 3 biomarkers allows neurotoxicity and thrombosis to be correlated with severity of cerebral ischemia and as such represents a promising additional tool for use with neuroimaging for the diagnosis of TIA/stroke. Development of a blood test that would also detect the thrombotic marker (anticardiolipin antibodies) observed by Brey et al1 would, when used in conjunction with our proposed biomarkers, help evaluate the thrombotic and neurotoxic contributions in stroke; guide antiplatelet, antithrombotic, and neuroprotective therapy; and assess patient follow-up and recovery after ischemic events.1 Brey RL, Abbott RD, Curb JD, Sharp DS, Ross GW, Stallworth CL, Kittner SJ. β2-glycoprotein 1-dependent anticardiolipin antibodies and the risk of ischemic stroke and myocardial infarction: the Honolulu Heart Program. Stroke. 2001; 32: 1701–1706.CrossrefMedlineGoogle Scholar2 Ziporen L, Shoenfeld Y. Antiphospholipid syndrome: from patient's bedside to experimental animal models and back to the patient's bedside. Hematol Cell Ther. 1998; 3: 247–251.Google Scholar3 Dambinova SA, Odinak MM, Skuliabin DI, Khounteev GA, Skvortsova VI. Laboratory methods in epilepsy and in disorders of cerebral circulation. Zh Nevrol Psihiatr Im S S Korsakova. 2001; 101: 58–64.lsqb; Russian].Google Scholar4 Thompson GA, Kilpatrick IC. The neurotransmitter candidature of sulfur-containing excitatory amino acids in the mammalian central nervous system. Pharmacol Ther. 1996; 72: 25–36.CrossrefMedlineGoogle Scholar5 Dambinova SA, Khounteev G, Zavolokov I, Ilyukhina A, Skoromets A. Glutamate, homocysteine and autoantibodies to NMDA receptor in patients with TIA and stroke. J Stroke Cerebrovasc Dis. 2001; 10: 194.Abstract.Google Scholar6 Khounteev GA, Zavolokov IG, Cherkas Yu V, Dambinova SA. Significance of the level of autoantibodies to NMDA type glutamate receptors in diagnosis of chronic cerebral circulation disorders. Zh Nevrol Psihiatr Im S S Korsakova. 2001; 11: 44–47.[Russian].Google Scholar7 Gusev EI, Skvortsova VI, Alekseev AA, Izykenova GA, Dambinova SA. Detection of autoantibodies to fragment of NMDA receptors in serum specimens from patients with acute brain ischemic stroke. Zh Nevrol Psihiatr Im S S Korsakova. 1996; 5: 68–72.[Russian].Google Scholar8 Gusev EI, Skvortsova VI, Dambinova SA, Raevskiy KS, Alekseev AA, Bashkatova VG, Kovalenko AV, Kudrin VS, Yakovleva EV. Neuroprotective effects of glycine for therapy of acute ischemic stroke. Cerebrovasc Dis. 2000; 10: 49–60.Google Scholar9 Izykenova G, Granstrem O, Gappoeva M, Dambinova S. Autoantibodies to NMDA receptor in chronic cerebral ischemia. J Stroke Cerebrovasc Dis. 2001; 10: 195.Abstract.Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Foschi M, Padroni M, Abu-Rumeileh S, Abdelhak A, Russo M, D'Anna L and Guarino M (2022) Diagnostic and Prognostic Blood Biomarkers in Transient Ischemic Attack and Minor Ischemic Stroke: An Up-To-Date Narrative Review, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2021.106292, 31:3, (106292), Online publication date: 1-Mar-2022. 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