Higher level of acute serum VEGF and larger infarct volume are more frequently associated with post-stroke cognitive impairment

Prodjohardjono, Astuti; Vidyanti, Amelia Nur; Susianti, Noor Alia; Sudarmanta,; Sutarni, Sri; Setyopranoto, Ismail

doi:10.1371/journal.pone.0239370

Cited by 28 publications

(20 citation statements)

References 58 publications

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“…Twenty-three studies (N ¼ 6273) reported acute stroke features. [11][12][13][14][15][18][19][20][21][22][23][24]26,[28][29][30][31][32][33][34][35][36]38 Studies reported highly heterogeneous features which we grouped into location, size, number of lesions, and swelling (Supplement 10). Evidence was heterogeneous; however, in general, there were no clear predictors of PSD or PSCI.…”

Section: Acute Stroke Featuresmentioning

confidence: 99%

Predicting post-stroke cognitive impairment using acute CT neuroimaging: A systematic review and meta-analysis

Ball

Sutherland

Squires

et al. 2021

International Journal of Stroke

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Background: Identifying whether acute stroke patients are at risk of cognitive decline could improve prognostic discussions and management. Structural computed tomography (CT) neuroimaging is routine in acute stroke, and may, identify those at risk of post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI). Aim: To systematically review the literature to identify which stroke or pre-stroke features on brain CT scans, performed at the time of stroke, are associated with PSD or PSCI. Summary of review: We searched electronic databases to December 2020. We included studies reporting acute stroke brain CT, and later diagnosis of a cognitive syndrome. We created summary estimates of size of unadjusted association between CT features and cognition. Of 9536 citations, twenty-eight studies (41 papers) were eligible (N=7078, mean age 59.8-78.6 years). Cognitive outcomes were PSD (10 studies), PSCI (17 studies), and one study analysed both. Fifteen studies (N=2952) reported data suitable for meta-analyses. White matter lesions (WML) (6 studies, N=1054, OR=2.46, 95% CI=1.25-4.84), cerebral atrophy (4 studies, N=558, OR=2.80, 95% CI=1.21-6.51), and pre-existing stroke lesions (3 studies, N=352, OR=2.38, 95% CI=1.06-5.32) were associated with PSD. WML (4 studies, N=473, OR=3.46, 95% CI=2.17-5.52) were associated with PSCI. Other CT features were either not associated with cognitive outcome, or there were insufficient data. Conclusions: Cognitive impairment following stroke is of great concern to patients and carers. Features seen on visual assessment of acute stroke CT brain scans are strongly associated with cognitive outcomes. Clinicians should consider when and how this information should be discussed with stroke survivors.

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Section: Acute Stroke Featuresmentioning

confidence: 99%

Predicting post-stroke cognitive impairment using acute CT neuroimaging: A systematic review and meta-analysis

Ball

Sutherland

Squires

et al. 2021

International Journal of Stroke

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“…The possible explanation could be associated with the early VEGF concentration and the severity of stroke. The correlation between higher level of VEGF and the augmented infarct volume [ 29 ] could confirm this hypothesis, indicating that the release of higher amount of VEGF is essential for reducing the consequences of an increased-damage zone in the brain tissue, thus not leading to deleterious effects. However, to confirm that hypothesis, further investigations are required.…”

Section: Angiogenic Biomarker Of Stroke Recoverymentioning

confidence: 89%

“…Pordjohardjono et al showed that a higher VEGF level was linked with an almost 5-fold higher incidence of cognitive impairment. Interestingly, cognitive impairment was positively associated with larger infarct volume [ 29 ]. On the other hand, the impact of rehabilitation on VEGF concentration was determined in a study conducted by Ma et al Results showed that running significantly elevated the level of VEGF and MMP2, and augmented the absolute regional cerebral blood flow in the ischemic area 16 days after stroke in animal models, thus having beneficial effects on long-term recovery [ 30 ].…”

Section: Angiogenic Biomarker Of Stroke Recoverymentioning

confidence: 99%

Biomarkers of Angiogenesis and Neuroplasticity as Promising Clinical Tools for Stroke Recovery Evaluation

Włodarczyk

Szelenberger

Cichoń

et al. 2021

IJMS

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Several key issues impact the clinical practice of stroke rehabilitation including a patient’s medical history, stroke experience, the potential for recovery, and the selection of the most effective type of therapy. Until clinicians have answers to these concerns, the treatment and rehabilitation are rather intuitive, with standard procedures carried out based on subjective estimations using clinical scales. Therefore, there is a need to find biomarkers that could predict brain recovery potential in stroke patients. This review aims to present the current state-of-the-art stroke recovery biomarkers that could be used in clinical practice. The revision of biochemical biomarkers has been developed based on stroke recovery processes: angiogenesis and neuroplasticity. This paper provides an overview of the biomarkers that are considered to be ready-to-use in clinical practice and others, considered as future tools. Furthermore, this review shows the utility of biomarkers in the development of the concept of personalized medicine. Enhancing brain neuroplasticity and rehabilitation facilitation are crucial concerns not only after stroke, but in all central nervous system diseases.

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“…The vascular endothelial growth factor (VEGF) family proteins, as well as other angiogenic factors, are also known to induce endothelial and neuronal remodeling after stroke ( Hayakawa et al, 2017 ). Levels of these proteins are elevated after ischemic insult in brain tissue and serum in rodent models and in humans ( Issa et al, 1999 ; Zhang et al, 2000 ; Prodjohardjono et al, 2020 ). However, few previous studies have evaluated whether changes in circulating angiogenic cells and proteins also occur in response to progressive and insidious cerebral SVD changes which commonly occur with advancing age.…”

Section: Introductionmentioning

confidence: 99%

Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease

Kapoor

Gaubert

Marshall

et al. 2021

Front. Aging Neurosci.

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Background: Cerebral small vessel disease (SVD) is associated with increased risk of stroke and dementia. Progressive damage to the cerebral microvasculature may also trigger angiogenic processes to promote vessel repair. Elevated levels of circulating endothelial progenitor cells (EPCs) and pro-angiogenic signaling proteins are observed in response to vascular injury. We aimed to examine circulating levels of EPCs and proangiogenic proteins in older adults with evidence of SVD.Methods: Older adults (ages 55–90) free of dementia or stroke underwent venipuncture and brain magnetic resonance imaging (MRI). Flow cytometry quantified circulating EPCs as the number of cells in the lymphocyte gate positively expressing EPC surface markers (CD34+CD133+CD309+). Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, and Flt-1). Total SVD burden score was determined based on MRI markers, including white matter hyperintensities, cerebral microbleeds and lacunes.Results: Sixty-four older adults were included. Linear regression revealed that older adults with higher circulating EPC levels exhibited greater total SVD burden [β = 1.0 × 105, 95% CI (0.2, 1.9), p = 0.019], after accounting for age and sex. Similarly, a positive relationship between circulating VEGF-D and total SVD score was observed, controlling for age and sex [β = 0.001, 95% CI (0.000, 0.001), p = 0.048].Conclusion: These findings suggest that elevated levels of circulating EPCs and VEGF-D correspond with greater cerebral SVD burden in older adults. Additional studies are warranted to determine whether activation of systemic angiogenic growth factors and EPCs represents an early attempt to rescue the vascular endothelium and repair damage in SVD.

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Higher level of acute serum VEGF and larger infarct volume are more frequently associated with post-stroke cognitive impairment

Cited by 28 publications

References 58 publications

Predicting post-stroke cognitive impairment using acute CT neuroimaging: A systematic review and meta-analysis

Predicting post-stroke cognitive impairment using acute CT neuroimaging: A systematic review and meta-analysis

Biomarkers of Angiogenesis and Neuroplasticity as Promising Clinical Tools for Stroke Recovery Evaluation

Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease

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