Cerebral small vessel disease: Pathological mechanisms and potential therapeutic targets

Gao, Yue; Li, Di; Lin, Jianwen; Thomas, Adrian; Miao, Jianyu; Chen, Dong; Shen, Li; Chu, Chengyan

doi:10.3389/fnagi.2022.961661

Cited by 51 publications

(24 citation statements)

References 123 publications

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“…29 This association could be explained by the shrinkage of thalamic dendrites and cell bodies due to the loss of synaptic input, 30 and the accumulation of microvascular damage in the thalamus. 31 We found that total thalamocortical connectivity was associated with the 3 cognitive domains (ie, processing speed, executive function, and memory). This finding is in line with previous studies showing the associations between WMH accumulation in the thalamic-cortical tract and processing speed.…”

Section: Discussionmentioning

confidence: 75%

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Dissociable Contributions of Thalamic-Subregions to Cognitive Impairment in Small Vessel Disease

Cai

Jacob

et al. 2023

Stroke

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Background: Structural network damage is a potentially important mechanism by which cerebral small vessel disease (SVD) can cause cognitive impairment. As a central hub of the structural network, the role of thalamus in SVD-related cognitive impairments remains unclear. We aimed to determine the associations between the structural alterations of thalamic subregions and cognitive impairments in SVD. Methods: In this cross-sectional study, 205 SVD participants without thalamic lacunes from the third follow-up (2020) of the prospective RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort), which was initiated in 2006, Nijmegen, were included. Cognitive functions included processing speed, executive function, and memory. Probabilistic tractography was performed from thalamus to 6 cortical regions, followed by connectivity-based thalamic segmentation to assess each thalamic subregion volume and connectivity (measured by mean diffusivity [MD] of the connecting white matter tracts) with the cortex. Least absolute shrinkage and selection operator regression analysis was conducted to identify the volumes or connectivity of the total thalamus and 6 thalamic subregions that have the strongest association with cognitive performance. Linear regression and mediation analyses were performed to test the association of least absolute shrinkage and selection operator-selected thalamic subregion volume or MD with cognitive performance, while adjusting for age and education. Results: We found that higher MD of the thalamic-motor tract was associated with worse processing speed (β=−0.27; P <0.001), higher MD of the thalamic-frontal tract was associated with worse executive function (β=−0.24; P =0.001), and memory (β=−0.28; P <0.001), respectively. The mediation analysis showed that MD of thalamocortical tracts mediated the association between corresponding thalamic subregion volumes and the cognitive performances in 3 domains. Conclusions: Our results suggest that the structural alterations of thalamus are linked to cognitive impairment in SVD, largely depending on the damage pattern of the white matter tracts connecting specific thalamic subregions and cortical regions.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Dissociable Contributions of Thalamic-Subregions to Cognitive Impairment in Small Vessel Disease

Cai

Jacob

et al. 2023

Stroke

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“… 26 , 27 In recent years, increasing evidence indicates an extraordinarily critical role of inflammation in the progression of WMH. 9 , 24 , 28 , 29 As a glycoprotein mediating inflammation, YKL-40 has been reported to correlated with pulmonary diseases, diabetes mellitus, coronary heart disease, Alzheimer’s disease and stroke. 10 , 11 , 14 However, evidence for the correlation between YKL-40 and CSVD is limited.…”

Section: Discussionmentioning

confidence: 99%

Serum YKL-40 Levels and White Matter Hyperintensities in Patients with Acute Ischemic Stroke

Shi¹,

Ke²,

Gong³

et al. 2023

JIR

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Background White matter hyperintensity (WMH) is associated with risk of acute ischemic stroke (AIS) and poor outcomes after AIS. The purpose of this prospective study was to evaluate the association between serum YKL-40 levels and WMH burden in patients with AIS. Methods From February 2020 to March 2021, a total of 672 consecutive AIS patients with magnetic resonance imaging data were prospectively recruited form two centers. Serum YKL-40 levels were quantified using enzyme-linked immunosorbent assay. The burden of WMH was semiquantitatively measured by the Fazekas visual grading scale. According to severity of overall WMH, patients were dichotomized into none–mild WMH group (Fazekas score 0–2) or moderate–severe WMH group (Fazekas score 3–6). Besides, based on severity of periventricular WMH (PV-WMH) and deep WMH (D-WMH), patients were categorized as none–mild (Fazekas score 0–1) or moderate–severe (Fazekas score 2–3). Results Among the 672 patients, 335 (49.9%) participants were identified with moderate–severe overall WMH, 326 (48.5%) with moderate–severe PV-WMH and 262 (39.0%) with moderate–severe D-WMH. Compared with the first quartile of serum YKL-40, the adjusted odds ratio (OR) of the fourth quartile for moderate–severe PV-WMH was 2.473 (95% confidence interval [CI] 1.316–4.646; P =0.005). No significant association was observed between YKL-40 and overall WMH (OR 0.762; 95% CI 0.434–1.336; P =0.343) or D-WMH (OR 0.695; 95% CI 0.413–1.171; P =0.172). Conclusion Our results suggested that higher YKL-40 levels appeared to be associated with PV-WMH, but not with overall WMH or D-WMH in patients with AIS.

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“…Болезнь малых сосудов головного мозга -это термин, используемый для обозначения различных патологических процессов, которые влияют на мелкие сосуды головного мозга, включая мелкие артерии, артериолы, капилляры и мелкие вены [3]. БМС может быть причиной лакунарных инфарктов мозга, возникающих в результате ишемии на территории перфорирующих артерий, а также причиной более диффузных ишемических изменений, которые принято называть лейкоареозом.…”

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Laboratory Markers of Hemostasis in Patients With Chronic Cerebral Ischemia

Khutorov¹

2022

СПНО (MPSE)

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Патофизиологической основой хронической ишемии головного мозга принято считать болезнь малых сосудов (БМС), которая является ведущим фактором возрастных изменений вещества головного мозга. БМС играет решающую роль в развитии лакунарного инсульта и других нейровизуализационных маркеров поражения, таких как гиперинтенсивность белого вещества, расширение периваскулярных пространств, атрофия головного мозга, недавние подкорковые инфаркты и микрокровоизлияния. Перечисленные изменения, в свою очередь, являются ведущей причиной когнитивного дефицита и функциональной потери у пожилых пациентов. Несмотря на то что патогенез поражения малых сосудов головного мозга до конца не изучен, считается, что в основе развития БМС лежит эндотелиальная дисфункция. Известно, что эндотелий играет важную роль в системе гемостаза, а его нарушение может приводить к гиперкоагуляционным состояниям. В этом обзоре мы сосредоточились на анализе литературных данных о наличии устойчивых взаимосвязей лабораторных биомаркеров гемостаза с прогрессированием БМС. По результатам обзора нам удалось показать, что, несмотря на то, что область изучения плазменных биомаркеров БМС находится на начальном этапе, уже опубликованы работы, где были показаны достоверные ассоциации между тканевым фактором, тканевым активатором плазминогена и ингибитором активатора плазмина. Также стоит отметить, что есть работы с противоположными результатами, оценивающими другие звенья гемостаза. Многие факторы оценивали отдельно, что формирует определенные ограничения, поэтому поиск панели биомаркеров, отражающих разные звенья системы гемостаза, формирует новую актуальную задачу в изучении патогенеза БМС. Ключевые слова: эндотелиальная дисфункция, гемостаз, болезнь малых сосудов, лабораторные маркеры.

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Cerebral small vessel disease: Pathological mechanisms and potential therapeutic targets

Cited by 51 publications

References 123 publications

Dissociable Contributions of Thalamic-Subregions to Cognitive Impairment in Small Vessel Disease

Dissociable Contributions of Thalamic-Subregions to Cognitive Impairment in Small Vessel Disease

Serum YKL-40 Levels and White Matter Hyperintensities in Patients with Acute Ischemic Stroke

Laboratory Markers of Hemostasis in Patients With Chronic Cerebral Ischemia

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