Anti-NR2 glutamate receptor antibodies as an early biomarker of cerebral small vessel disease |
| |
| Institution: | 1. Research Center of Neurology, 80 Volokolamskoe shosse, 125367 Moscow, Russia;2. Federal State Autonomous Institution «N. N. Burdenko National Medical Research Center of Neurosurgery of the Ministry of Health of the Russian Federation, 16 4th Tverskaya-Yamskaya St., Moscow, Russia;1. Section for Forensic Chemistry, Department of Forensic Medicine, Aarhus University, Denmark;2. Department of Infectious Diseases, Aarhus University Hospital, Denmark;3. Department of Clinical Pharmacology, Aarhus University Hospital, Denmark;4. DANDRITE, Department of Biomedicine, Aarhus University, Denmark;5. Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark;1. Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, United States;2. Family Fertility Center, Texas Children’s Hospital, Houston, TX, United States;3. Department of Pathology, Texas Children’s Hospital, Houston, TX, United States;1. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, United States;2. Division of Cardiology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, United States;3. Division of Emergency Medicine, McMaster University, Hamilton, ON, Canada;4. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada;1. Department of Anesthesiology & Pain Medicine, University of Alberta, 2-150 Clinical Sciences Building (CSB) 8440 112 St NW, Edmonton, Alberta T6G 2G3, Canada;2. Department of Community Health Sciences, Cumming School of Medicine, Teaching, Research and Wellness Building, 5E25-3280 Hospital Drive NW, Calgary, Alberta T2N 4Z6, Canada;3. Department of Pathology and Laboratory Medicine, Cumming School of Medicine, Health Sciences Centre, Foothills Campus, University of Calgary, 3030 Hospital Drive NW, Calgary, AB T2N 4N1, Canada;4. Alberta Precision Laboratories, Diagnostic and Scientific Research Centre, #9 3535 Research Way NW, Calgary, AB T2L 2K8, Canada;5. Department of Cardiac Sciences, Cumming School of Medicine, Health Sciences Centre, Foothills Campus, University of Calgary, 3030 Hospital Drive NW, Calgary, AB T2N 4N1, Canada |
| |
| Abstract: | ObjectivesCerebral small vessel disease (SVD) associated with age and vascular risk factors is one of the leading causes of cognitive disorders as well as ischemic and hemorrhagic strokes. The pathogenesis of this disease has not been fully understood yet. The previously established association of the antibodies against the NR2 subunit of the NMDA receptor (NR2ab) with the mechanisms of SVD such as ischemia and blood–brain barrier (BBB) disruption, might suggest their importance in the brain damage.Design & methodsWe studied the NR2ab serum level in 70 patients (45 females, 61.1 ± 6.3 y.o.) with different severity of cognitive impairment and MRI features of SVD and 20 healthy volunteers (12 females, 58.5 ± 6.4 y.o.).ResultsThe elevated level of NR2ab was associated with subjective cognitive impairment (SCI) (p = 0.028) and mild cognitive impairment (MCI) (p = 0.017), Fazekas grade (F) 2 (p = 0,002) and F3 (p = 0,009) of white matter hyperintensities (WMH) and the numbers of lacunes in the cerebral white matter (less than 5) (p = 0,039).ConclusionThe detected increase in serum NR2ab level in patients with SCI, as well as the minimal amount of white matter lacunes, is most likely caused by hypoxia-induced endothelial damage in the early stage of SVD. Normal NR2ab values in patients with F1 WMH, the increased NR2ab level in patients with F2 and F3 WMH and those with the minimal number of lacunes can indicate that NR2bs are involved in diffuse brain damage due to hypoxia-induced loss of BBB integrity. |
| |
| Keywords: | Cerebral small vessel disease Glutamate Anti-NR2 antibodies Cognitive impairment White matter hyperintensity Endothelial dysfunction Blood-brain barrier permeability |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
