Macrophage- and Microglia-Related Chemokines Are Associated with Small Vessel (White Matter) Vascular Dementia: A Case-Control Study

2021 ◽  
pp. 1-6
Author(s):  
Ren Fen Chen ◽  
Nady Braidy ◽  
Ying Hua Xu ◽  
Sarah Tan ◽  
Daniel Kam Yin Chan
Keyword(s):  
White Matter ◽  
Vascular Dementia ◽  
Causal Effect ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Small Vessel ◽  
Vascular Pathology ◽  
Memory Disorder ◽  
Interleukin 7 ◽  
Cytokines And Chemokines

<b><i>Introduction:</i></b> Little is known about the role of inflammation in the process of small vessel vascular dementia (VaD). Recently, the notion that small vessel VaD is caused solely by vascular pathology has been challenged by new evidence of concomitant breakdown of the blood-brain barrier and dysregulation of neuroinflammation in the white matter. <b><i>Methods:</i></b> We examined selected inflammatory cytokines and chemokines in the plasma from patients with small vessel VaD (<i>n</i> = 41) and from age-matched controls (<i>n</i> = 131) using multiplex bead-based assays. Participants were recruited from a memory disorder clinic and from a hospital or community. <b><i>Results:</i></b> When compared to controls, patients with small vessel VaD had a highly significant increase in the plasma interferon-γ-inducible protein 10 (IP-10) level (<i>p</i> &#x3c; 0.0001) and a highly significant decrease in plasma macrophage inflammatory protein 1-beta (MIP-1β) level (<i>p</i> &#x3c; 0.0001). We also observed a significant increase in patients’ levels of interleukin-10 (IL-10) (<i>p</i> = 0.022) as well as decreases in interleukin-8 (IL-8) (<i>p</i> = 0.004) and interleukin-7 (IL-7) (<i>p</i> = 0.011) when compared to age-matched controls. <b><i>Conclusion:</i></b> Both IP-10 and MIP-1β are macrophage-related chemokines. The significant differences between cases and controls suggest a potential role for macrophages in small vessel VaD neuroinflammation. Although it remains unclear whether there is a causal effect of their alteration for small vessel VaD, a better understanding of these molecules in the pathogenesis of small vessel VaD may lead to improved diagnosis and future treatment outcomes against this disease.

scholarly journals Microglia control small vessel calcification via TREM2

2021 ◽  
Vol 7 (9) ◽  
pp. eabc4898
Author(s):  
Yvette Zarb ◽  
Sucheta Sridhar ◽  
Sina Nassiri ◽  
Sebastian Guido Utz ◽  
Johanna Schaffenrath ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Vascular Calcification ◽  
Neurovascular Unit ◽  
Small Vessel ◽  
Vascular Pathology ◽  
Cns Development ◽  
Brain Calcification

Microglia participate in central nervous system (CNS) development and homeostasis and are often implicated in modulating disease processes. However, less is known about the role of microglia in the biology of the neurovascular unit (NVU). In particular, data are scant on whether microglia are involved in CNS vascular pathology. In this study, we use a mouse model of primary familial brain calcification, Pdgfbret/ret, to investigate the role of microglia in calcification of the NVU. We report that microglia enclosing vessel calcifications, coined calcification-associated microglia, display a distinct activation phenotype. Pharmacological ablation of microglia with the CSF1R inhibitor PLX5622 leads to aggravated vessel calcification. Mechanistically, we show that microglia require functional TREM2 for controlling vascular calcification. Our results demonstrate that microglial activity in the setting of pathological vascular calcification is beneficial. In addition, we identify a previously unrecognized function of microglia in halting the expansion of vascular calcification.

Higher Cerebral Small Vessel Disease Burden in Patients with White Matter Recent Small Subcortical Infarcts

2021 ◽  
Vol 30 (7) ◽  
pp. 105824
Author(s):  
Salvatore Rudilosso ◽  
Luis Mena ◽  
Diana Esteller ◽  
Marta Olivera ◽  
Juan José Mengual ◽  
...  
Keyword(s):  
White Matter ◽  
Disease Burden ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease

scholarly journals Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions

2017 ◽  
Vol 9 ◽  
Author(s):  
Kyle C. Kern ◽  
Clinton B. Wright ◽  
Kaitlin L. Bergfield ◽  
Megan C. Fitzhugh ◽  
Kewei Chen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
White Matter ◽  
Blood Pressure Control ◽  
Cerebral Atrophy ◽  
White Matter Lesions ◽  
Pressure Control ◽  
Small Vessel

scholarly journals KSR1 Protects From Interleukin-10 Deficiency-Induced Colitis in Mice by Suppressing T-Lymphocyte Interferon-γ Production

2011 ◽  
Vol 140 (1) ◽  
pp. 265-274 ◽  
Author(s):  
Jeremy A. Goettel ◽  
Holly M. Scott Algood ◽  
Danyvid Olivares–Villagómez ◽  
M. Kay Washington ◽  
Rupesh Chaturvedi ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Interleukin 10 ◽  
Interferon Γ

Are Gait Disturbances and White Matter Degeneration Early Indicators of Vascular Dementia?

1994 ◽  
Vol 5 (3-4) ◽  
pp. 197-202 ◽  
Author(s):  
Michael G. Hennerici ◽  
Manfred Oster ◽  
Simon Cohen ◽  
Andreas Schwartz ◽  
Lillian Motsch ◽  
...  
Keyword(s):  
White Matter ◽  
Vascular Dementia ◽  
White Matter Degeneration ◽  
Gait Disturbances ◽  
Early Indicators

Abstract WMP78: The Efficacy of Angiotensin II Peptide Vaccination Against White Matter Lesions of Vascular Dementia in Rats

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Kouji Wakayama ◽  
Munehisa Shimamura ◽  
Hironori Nakagami ◽  
Ryuichi Morishita
Keyword(s):  
Endothelial Cells ◽  
Cognitive Function ◽  
Angiotensin Ii ◽  
White Matter ◽  
Western Blot ◽  
Vascular Dementia ◽  
White Matter Lesions ◽  
Ang Ii ◽  
Peptide Vaccination ◽  
Brdu Assay

Background & Purposes: There had been no attempt to show the efficacy of therapeutic vaccination in vascular dementia. A rat model of vascular dementia was prepared by bilateral common carotid artery ligation (2VO). The purpose of this study is to investigate whether pre-exposure Angiotensin II (Ang II) peptide vaccination exhibits the protective effects against white matter lesions (WML) in 2VO rats. Methods: After subcutaneous injection of Ang II peptide vaccine (10μg/200μl) or saline (200μl) to Wistar rats (male) at the time point of 6, 8 and 10 week-old, 2VO or sham surgery was performed at 12 week-old. Cognitive function was evaluated after 14 days of 2VO using the novel object recognition (NOR) test. Anti-Ang II antibody (Ab) level was quantified using ELISA. Histological examinations of WML and demyelination in the corpus callosum (CC) were evaluated using immunohistochemistry (IHC), 5-bromodeoxyuridine (BrdU) assay and Klüver-Barrera staining. Western blot analyses of VCAM-1, FGF2, phospho-CREB and CREB using proteins extracted from CC were performed to investigate the mechanism of restoration of WML by Ang II vaccination. Results: Histological examinations presented that exacerbation of WML and demyelination observed in saline treated (S) rats was ameliorated in Ang II vaccinated (V) rats. The results of NOR test indicated that cognitive dysfunction observed in S rats was improved in V rats at 14 days after 2VO. Expression of VCAM-1 in CC of S rats was significantly reduced in V rats at 7 days after 2VO. BrdU assay exhibited that vaccination accelerated the differentiation of oligodendrocyte progenitor cells (OPCs) in WML from 14 days to 28 days of 2VO. Western blot presented that both CREB phosphorylation and FGF2 expression in CC were increased in V rats compared with S rats at 14 days after 2VO. Double IHC showed that FGF2 expressing cells were mostly endothelial cells and astrocytes in WML. Conclusions: Ang II vaccination restored WML as well as cognitive function in 2VO rats. Our findings suggested that Ang II vaccination ameliorated cerebrovascular endothelial dysfunction which could accelerate the OPCs differentiation through increased expression of FGF2 in endothelial cells or astrocytes in 2VO rats.

Abstract TP201: The Relationship Between Chronic Kidney Diseases and the Presence of Cerebral Small Vessel Disease in Patients With Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Kana Ueki ◽  
Asako Nakamura ◽  
Masahiro Yasaka ◽  
Takahiro Kuwashiro ◽  
Seiji Gotoh ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
White Matter Lesion ◽  
Kidney Diseases ◽  
Univariate Analysis ◽  
Small Vessel ◽  
Chronic Kidney Diseases ◽  
History Of ◽  
The Relationship

Introduction: Cerebral small vessel diseases (SVDs) i.e. white matter lesion and cerebral microbleeds (CMBs) are related to the patients with stroke more deeply than those without. In general population, in addition to age, hypertension, diabetes chronic kidney diseases (CKD) is well known to be related to SVDs, but it remains unclear in patients with stroke. We investigated the relationship between CKD and the presence of SVDs in patients with acute ischemic stroke. Methods: We enrolled 493 patients with acute ischemic stroke patients or transient ischemic attack patients (mean age 71; 60% male) who had undergone 1.5T MR imaging within a week of the index events from April 2013 to march 2015. We evaluated kidney function by estimated glomerular filtration rate (eGFR) with the modification of diet in Renal Disease. CKD was defined as an eGFR less than 60mil/min/1.73m 2 . CMBs were defined as focal areas of very low signal intensity smaller than 10mm. White matter lesion as Periventricular hyper intensity (PVH)>grade 2 and Deep and Subcortical White Matter Hyper intensity (DSWMH)> grade 2 were defied as advanced PVH and advanced DSWMH, respectively. We investigated relationship between CKD and CMBs, advanced PVH and advanced DSWMH using a logistic regression analysis. Results: We noted CMBs in 173 patients (35%), PVH in 81 (16%), and DSWMH in 151 (31%). An univariate analysis revealed that the age, CKD, history of stroke, and antiplatelet agents were associated with presence of CMBs, advanced PVH and severe DSWMH . The multivariate analysis revealed that CMBs, advanced PVH and advanced DSWMH were associated with age (CMBs: odds ratio(OR) ; 1.32 ; 95% confidence interval(CI), 1.10-1.60, p=0.004, advanced PVH : OR ; 3.00 ; 95% CI, 2.17-4.26, p<0.01, advanced DSWMH: OR ; 1.94; 95% CI, 1.56-2.45, p<0.01 ), history of stroke(CMBs : OR ; 2.01 ; 95% CI, 1.21-3.34, p=0.007, advanced PVH : OR ; 2.25 ; 95% CI, 1.18-4.27, p=0.01, advanced DSWMH: OR ; 1.78 ; 95% CI, 1.03-3.06, p=0.038). CKD was associated with CMBs (OR ; 1.62 ; 95% CI, 1.04-2.52, p=0.03), but PVH and DSWMH were not. Conclusions: It seems that age and history of stroke are related to CMBs, advanced PVH and advanced DSWMH, and that CKD is associates with CMBs but not with either advanced PVH or advanced DSWMH.

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