Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown

Warden, Antony R.; Ahmad, Khalil; Liu, Yanlei; He, Xijun; Zheng, Min-qiao; Huo, Xinlong; Zhi, Xiao; Ke, Yuqing; Li, Hongxia; Yan, Sijia; Su, Wenqiong; Cai, David; Li, Yiyang

doi:10.34133/2021/9873545

Cited by 6 publications

(5 citation statements)

References 78 publications

(88 reference statements)

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“…The number of circulating neural cells (CNCs) may also serve as a severity/progression real‐time indicator. In a 1‐h tMCAO mice model and in the peripheral blood of ischemic patients, the CNCs levels were significantly higher, specifically the NeuN + /CD45 − /DAPI + cells 66 …”

Section: Resultsmentioning

confidence: 95%

“…In a 1-h tMCAO mice model and in the peripheral blood of ischemic patients, the CNCs levels were significantly higher, specifically the NeuN + /CD45 − /DAPI + cells. 66 Overall, these were exploratory studies with limited translation to the human setting. Taking these results and observations in animals, together with the translational studies with positive results in human patients, it seems that there are already biomarker candidates with the potential to be applied in the clinical setting.…”

Section: Othersmentioning

confidence: 99%

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Fluid biomarkers in stroke: From animal models to clinical care

Dias

Silva

Moura

et al. 2022

Acta Neuro Scandinavica

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Stroke is a leading cause of death and disability worldwide. Stroke prevention, early diagnosis, and efficient acute treatment are priorities to successfully impact stroke death and disability. Fluid biomarkers may improve stroke differential diagnostic, patient stratification for acute treatment, and post‐stroke individualized rehabilitation. In the present work, we characterized the use of stroke animal models in fluid biomarker research through a systematic review of PubMed and Scopus databases, followed by a literature review on the translation to the human stroke care setting and future perspectives in the field. We found increasing numbers of publications but with limited translation to the clinic. Animal studies are very heterogeneous, do not account for several human features present in stroke, and, importantly, only a minority of such studies used human cohorts to validate biomarker findings. Clinical studies have found appealing candidates, both protein and circulating nucleic acids, to contribute to a more personalized stroke care pathway. Still, brain tissue complexity and the fact that different brain pathologies share lesion biomarkers make this task challenging due to biomarker low specificity. Moreover, the study design and lack of validation cohorts may have precluded a formal integration of biomarkers in different steps of stroke diagnosis and treatment. To overcome such issues, recent pivotal studies on biomarker dynamics in individual patients are providing added value to diagnosis and anticipating patients' early prognosis. Presently, the most consistent protein biomarkers for stroke diagnosis and short‐ and long‐term prognosis are associated with tissue damage at neuronal (TAU), axonal (NFL), or astroglial (GFAP and S100β) levels. Most promising nucleic acids are microRNAs (miR), due to their stability in plasma and ease of access. Still, clinical validation and standardized quantitation place them a step behind compared protein as stroke biomarkers. Ultimately, the definition of clinically relevant biomarker panels and optimization of fast and sensitive biomarker measurements in the blood, together with their combination with clinical and neuroimaging data, will pave the way toward personalized stroke care.

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Section: Resultsmentioning

confidence: 95%

Section: Othersmentioning

confidence: 99%

Fluid biomarkers in stroke: From animal models to clinical care

Dias

Silva

Moura

et al. 2022

Acta Neuro Scandinavica

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“…NR2B is an essential subunit of NMDARs, plays a crucial role in neuronal excitability, and is associated with the learning and memory function of the nervous system. Increased expression or activation of NR2B could revert the learning and memory abilities of mice with impaired cognitive function [ 22 , 23 ]. To confirm the details of THz photon absorption, we calculated from molecular dynamics simulations that the absorption spectrum of the glutamate-binding pocket of NR2B shows a clear fingerprint peak near 34.5 ± 1 THz, while this main absorption peak was located for glutamate molecules (Fig.…”

Section: Resultsmentioning

confidence: 99%

Terahertz Photons Improve Cognitive Functions in Posttraumatic Stress Disorder

Yu,

Wu,

Yang

et al. 2023

Research

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Posttraumatic stress disorder (PTSD) is a serious psychosis leading to cognitive impairment. To restore cognitive functions for patients, the main treatments are based on medication or rehabilitation training but with limited effectiveness and strong side effects. Here, we demonstrate a new treatment approach for PTSD by using terahertz (THz) photons stimulating the hippocampal CA3 subregion. We verified that this method can nonthermally restore cognitive function in PTSD rats in vivo. After THz photon irradiation, the PTSD rats’ recognitive index improved by about 10% in a novel object recognition test, the PTSD rats’ accuracy improved by about 100% in a shuttler box test, the PTSD rats’ numbers to identify target box was about 5 times lower in a Barnes maze test, and the rate of staying in new arm increased by approximately 40% in a Y-maze test. Further experimental studies found that THz photon (34.5 THz) irradiation could improve the expression of NR2B (increased by nearly 40%) and phosphorylated NR2B (increased by about 50%). In addition, molecular dynamics simulations showed that THz photons at a frequency of 34.5 THz are mainly absorbed by the pocket of glutamate receptors rather than by glutamate molecules. Moreover, the binding between glutamate receptors and glutamate molecules was increased by THz photons. This study offers a nondrug, nonthermal approach to regulate the binding between the excitatory neurotransmitter (glutamate) and NR2B. By increasing synaptic plasticity, it effectively improves the cognitive function of animals with PTSD, providing a promising treatment strategy for NR2B-related cognitive disorders.

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“…Transient middle cerebral artery occlusion (MCAO) model was induced based on previous literature as described [ 74 , 75 ]. Briefly, mice were deeply anesthetized with 1% pentobarbital and then secured onto a plastic board while they were unresponsive to tail pinch tests.…”

Section: Methodsmentioning

confidence: 99%

Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain

Lu,

Li,

Zhang

et al. 2023

Research

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Immunosenescence refers to the multifaceted and profound alterations in the immune system brought about by aging, exerting complex influences on the pathophysiological processes of diseases that manifest upon it. Using a combination of single-cell RNA sequencing, cytometry by time of flight, and various immunological assays, we investigated the characteristics of immunosenescence in the peripheral blood of aged mice and its impact on the cerebral immune environment after ischemic stroke. Our results revealed some features of immunosenescence. We observed an increase in neutrophil counts, concurrent with accelerated neutrophil aging, characterized by altered expression of aging-associated markers like CD62L and consequential changes in neutrophil-mediated immune functions. Monocytes/macrophages in aged mice exhibited enhanced antigen-presentation capabilities. T cell profiles shifted from naive to effector or memory states, with a specific rise in T helper 1 cells and T helper 17 cells subpopulations and increased regulatory T cell activation in CD4 T cells. Furthermore, regulatory CD8 T cells marked by Klra decreased with aging, while a subpopulation of exhausted-like CD8 T cells expanded, retaining potent immunostimulatory and proinflammatory functions. Critically, these inherent disparities not only persisted but were further amplified within the ischemic hemispheres following stroke. In summary, our comprehensive insights into the key attributes of peripheral immunosenescence provide a vital theoretical foundation for understanding not only ischemic strokes but also other age-associated diseases.

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Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown

Cited by 6 publications

References 78 publications

Fluid biomarkers in stroke: From animal models to clinical care

Fluid biomarkers in stroke: From animal models to clinical care

Terahertz Photons Improve Cognitive Functions in Posttraumatic Stress Disorder

Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain

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