Anti-NR2 glutamate receptor antibodies as an early biomarker of cerebral small vessel disease

Dobrynina, Larisa А.; Alexandrova, E. V.; Zabitova, Maryam R.; Калашникова, Л А; Кротенкова, М. В.; Akhmetzyanov, Bulat M.

doi:10.1016/j.clinbiochem.2021.07.003

Cited by 4 publications

(5 citation statements)

References 62 publications

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“…In CCH, however, endothelial cells are dysregulated. An increase of serum antibodies against the NR2 subunit of the NMDA receptor (NR2ab), probably due to endothelial damage in the early stage of SVD, was confirmed in patients with subjective cognitive impairment ( Dobrynina et al, 2021 ). In vitro studies also observed endothelial injury and BBB dysfunction in CCH rats with worse performance in the Morris water maze test ( Ueno et al, 2009 ).…”

Section: Updated Evidence Of Blood–brain Barrier Dysfunction Mechanis...mentioning

confidence: 94%

Blood–Brain Barrier Dysfunction and the Potential Mechanisms in Chronic Cerebral Hypoperfusion Induced Cognitive Impairment

Bai

Dong

et al. 2022

Front. Cell. Neurosci.

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Chronic cerebral hypoperfusion (CCH) is a major cause of vascular cognitive impairment and dementia (VCID). Although the underlying mechanisms have not been fully elucidated, the emerging data suggest that blood–brain barrier (BBB) dysfunction is one of the pivotal pathological changes in CCH. BBB dysfunction appears early in CCH, contributing to the deterioration of white matter and the development of cognitive impairment. In this review, we summarize the latest experimental and clinical evidence implicating BBB disruption as a major cause of VCID. We discuss the mechanisms of BBB dysfunction in CCH, focusing on the cell interactions within the BBB, as well as the potential role of APOE genotype. In summary, we provide novel insights into the pathophysiological mechanisms underlying BBB dysfunction and the potential clinical benefits of therapeutic interventions targeting BBB in CCH.

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Section: Updated Evidence Of Blood–brain Barrier Dysfunction Mechanis...mentioning

confidence: 94%

Blood–Brain Barrier Dysfunction and the Potential Mechanisms in Chronic Cerebral Hypoperfusion Induced Cognitive Impairment

Bai

Dong

et al. 2022

Front. Cell. Neurosci.

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“…Elkind [13] 1244 lacunar stroke CRP RSSI Jiyang Jiang [14] 327 elderly participants aged 70 to 90 years MIC-1/GDF15 WMH Charlotte Andersson [15] 3374 Framingham Offspring GDF15, ST2 WMH, brain atrophy Arnab Datta [16] 45 lacunar stroke proteomic RSSI Andrea Vilar-Bergua [17] 972 hypertension N-glycome Profile WMH [19] 324 CIND; AD GDF15 WMH, RSSI, lacune Amelia K. Boehme [20] 1244 lacunar stroke IL-6, amyloid A, TNFR1, CD40L, MCP1 RSSI Li Yang [21] 56 lacunar stroke Lipidomic RSSI Yanan Zhu [22] 315 CIND; AD t IL-6, IL-8, TNF-α WMH, RSSI, lacune Thomas Gattringer [23] 579 RSSI NfL WMH, RSSI Ki-Woong Nam [24] 2875 people with a health check-up NLR WMH Huimin Fan [25] 389 lacunar stroke Homocysteine RSSI Huang Guoxiang [26] 408 noncritically ill hospitalized patients Cystatin C WMH Jacek Staszewski [27] 123 CSVD vascular and systemic inflammation biomarkers WMH, lacune Daniela Pinter [28] 78 RSSI NfL RSSI Simon R. Cox [29] 593 elderly participants aged 73 to 76 years S100β WMH Esther M.C. van Leijsen [30] 487 CSVD Aβ WMH, CMB, lacune Weimin Wei [31] 346 hypertension BNP WMH, CMB, RSSI Yanan Zhu [32] 310 CIND; AD HGF WMH, CMB, RSSI, lacune Emer R. McGrath [33] 1603 Framingham Offspring GDF-15, NT-proBNP WMH, brain atrophy Yan Sun [34] 1029 CIND NfL WMH Peng Xu [35] 12 lacunar stroke miR-133, IL-6, IL-8, CRP, TNF-α RSSI Larisa A. Dobrynina [36] 70 CSVD NR2ab WMH, lacune Yi Qu [37] 496 CIND NfL WMH, CMB, RSSI, CSVD burden Alison E Fohner [38] 1362 elderly participants aged 65 years or older NfL, total Tau, GFAP, UCH-L1 WMH Bibek Gyanwali [39] 434 CIND NT-proBNP, hs-cTnT, GDF-15 WMH, CMB, RSSI, lacune Joan Jiménez-Balado [40] 24 hypertension proteomic WMH Yuek Ling Chai [41] 384 CIND; AD OPN WMH, brain atrophy Andres da Silva-Candal [42] 624 hypertension or diabetes w TWEAK WMH Sanne Kuipers [43] 494…”

Section: Yearmentioning

confidence: 99%

“…Researchers infer that sTWEAK contributes to WMH, possibly by inducing the over-expression of proinflammatory cytokines and disrupting the structure and function of the BBB [ 67 ]. In addition, the elevated level of antibodies against the NMDA receptor NR2 subunit (NR2ab) is associated with the Fazekas scale of WMH [ 36 ]. NR2ab, located in the endothelium of the cerebral arteries [ 68 ], potentially leads to excitotoxicity processes that cause damage to the BBB’s integrity [ 69 ].…”

Section: Search Strategymentioning

confidence: 99%

“…BBB dysfunction A study has investigated the possibility that an elevated NMDA receptor NR2 subunit (NR2ab) level is related to the number of lacunes (less than 5) ( p = 0.039) [ 36 ]. The dysfunctional BBB may better explain the potential role of these receptors and the way that they lead to the appearance and development of lacunes [ 73 ].…”

Section: Search Strategymentioning

confidence: 99%

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Correlations of Plasma Biomarkers and Imaging Characteristics of Cerebral Small Vessel Disease

Kong,

Xie,

Wang

et al. 2024

Brain Sciences

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Cerebral small vessel disease (CSVD), which is a group of pathological processes affecting cerebral microvessels, leads to functional loss in the elderly population and mostly presents as cognitive impairment and gait decline. CSVD is diagnosed based on brain imaging biomarkers, but blood biomarkers are of great significance for the early diagnosis and progression prediction of CSVD and have become a research focus because of their noninvasiveness and easy accessibility. Notably, many blood biomarkers have been reported to be associated with CSVD in a relatively large population, particularly serum neurofilament light chain (NfL), which has been regarded as a promising biomarker to track the variation trend in WMH and to predict the further status of white matter hyperintensities (WMH) and lacunar infarcts. And neuro-glio-vascular unit structure and blood–brain barrier function have been proposed as underlying mechanisms of CSVD. The article starts from the neuroimaging markers of CSVD, including recent small subcortical infarcts (RSSI), white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), enlarged perivascular spaces (EPVS), cerebral atrophy, and the combined small vessel disease score, and attempts to systematically review and summarize the research progress regarding the blood biomarkers of CSVD that form the changes in the neuro-glio-vascular unit structure and blood–brain barrier function.

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“…NSE, an isoenzyme of the glycolytic enzyme enolase, can also be employed as a marker for ischemic stroke, intracranial hemorrhage, and traumatic brain injury, indicating changes in neuronal activity [ 45 , 46 ]. In turn, another serum biomarker—antibodies against the NR2 subunit of the NMDA receptor (NR-2-ab)—has been demonstrated to be a potential biomarker for ischemic stroke [ 47 ] and cerebral small vessel disease [ 48 ]. All of the abovementioned results determined the choice of these molecules for the current study.…”

Section: Introductionmentioning

confidence: 99%

Elevated Levels of Serum Biomarkers Associated with Damage to the CNS Neurons and Endothelial Cells Are Linked with Changes in Brain Connectivity in Breast Cancer Patients with Vestibulo-Atactic Syndrome

Nikolaeva,

Pospelova,

Krasnikova

et al. 2023

Pathophysiology

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Vestibulo-atactic syndrome (VAS), which represents a combination of motor and vestibular disorders, can be manifested as a clinical complication of breast cancer treatment and has a significant impact on patients’ quality of life. The identification of novel potential biomarkers that might help to predict the onset of VAS and its progression could improve the management of this group of patients. In the current study, the levels of intercellular cell adhesion molecule 1 (ICAM-1), platelet/endothelial cell adhesion molecule 1 (PECAM-1), NSE (neuron-specific enolase), and the antibodies recognizing NR-2 subunit of NMDA receptor (NR-2-ab) were measured in the blood serum of BC survivor patients with vestibulo-atactic syndrome (VAS) and associated with the brain connectome data obtained via functional magnetic resonance imaging (fMRI) studies. A total of 21 patients were registered in this open, single-center trial and compared to age-matched healthy female volunteers (control group) (n = 17). BC patients with VAS demonstrated higher serum levels of ICAM-1, PECAM-1, and NSE and a lower value of NR-2-ab, with values of 654.7 ± 184.8, 115.3 ± 37.03, 49.9 ± 103.9, and 0.5 ± 0.3 pg/mL, respectively, as compared to the healthy volunteers, with 230.2 ± 44.8, 62.8 ± 15.6, 15.5 ± 6.4, and 1.4 ± 0.7 pg/mL. According to the fMRI data (employing seed-to-voxel and ROI-to-ROI methods), in BC patients with VAS, significant changes were detected in the functional connectivity in the areas involved in the regulation of postural-tonic reflexes, the coordination of movements, and the regulation of balance. In conclusion, the detected elevated levels of serum biomarkers may reveal damage to the CNS neurons and endothelial cells that is, in turn, associated with the change in the brain connectivity in this group of patients.

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Anti-NR2 glutamate receptor antibodies as an early biomarker of cerebral small vessel disease

Cited by 4 publications

References 62 publications

Blood–Brain Barrier Dysfunction and the Potential Mechanisms in Chronic Cerebral Hypoperfusion Induced Cognitive Impairment

Blood–Brain Barrier Dysfunction and the Potential Mechanisms in Chronic Cerebral Hypoperfusion Induced Cognitive Impairment

Correlations of Plasma Biomarkers and Imaging Characteristics of Cerebral Small Vessel Disease

Elevated Levels of Serum Biomarkers Associated with Damage to the CNS Neurons and Endothelial Cells Are Linked with Changes in Brain Connectivity in Breast Cancer Patients with Vestibulo-Atactic Syndrome

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