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Molecular, Cellular, and Blood Biomarkers in Acute Ischemic Stroke
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Molecular, Cellular, and Blood Biomarkers in Acute Ischemic Stroke

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 8271

Special Issue Editor

Dr. Sonu M. M. Bhaskar

E-Mail Website
Guest Editor
1. Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan
2. Global Health Neurology Lab, Sydney, NSW 2000, Australia
3. NSW Brain Clot Bank, Sydney, NSW, Australia
Interests: cerebrovascular disorders; stroke; biomarkers; cardiovascular diseases; global health; social inequalities in health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stroke is a leading cause of death and disability in the world. The advent of thrombolysis and endovascular thrombectomy has revolutionized the field of stroke medicine. However, despite these advances, unfortunately, these treatments are accessed by, or available to, only a limited subgroup of patients. Several stroke patients live with lifelong disabilities. In this context, the identification of molecular, cellular, and blood biomarkers could contribute to the diagnosis, prognosis, and management of acute ischemic stroke patients. From transcriptomic signatures based on the detection of differential expression of genes, brain clot composition, and novel imaging biomarkers to the application of machine learning to epigenomic, transcriptomic, proteomic, and metabolomic taxonomy of acute ischemic stroke could assist in stratifying patients into groups and inform prognostic and therapeutic strategies. We invite submissions on a broad range of topics – including but not limited to exploratory or fundamental scientific studies, pre-clinical, cross-sectional studies, clinical trials, position papers/recommendations, hypothesis/perspective, systematic and narrative/comprehensive review on the novel, emerging and existing molecular, cellular and blood biomarkers in acute ischemic stroke.

Dr. Sonu M. M. Bhaskar
Guest Editor

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Keywords

  • stroke
  • cerebrovascular disorders
  • reperfusion
  • biomarkers
  • discovery
  • translational neuroscience
  • blood
  • molecular
  • imaging
  • cerebral ischemia
  • genomics
  • proteomics

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Published Papers (4 papers)

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Research

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19 pages, 2288 KiB  
Article
Astrocyte Dysfunction Reflected in Ischemia-Induced Astrocyte-Derived Extracellular Vesicles: A Pilot Study on Acute Ischemic Stroke Patients
by Timea Forró, Doina Ramona Manu, Lucian Barbu-Tudoran and Rodica Bălașa
Int. J. Mol. Sci. 2024, 25(22), 12471; https://doi.org/10.3390/ijms252212471 - 20 Nov 2024
Viewed by 246
Abstract
Extracellular vesicles (EVs) secreted by astrocytes (ADEVs) mediate numerous biological processes, providing insights into damage, repair, and protection following ischemic stroke (IS). This pilot study aimed to broaden the current knowledge on the astrocyte response to ischemia by dynamically assessing the aquaporin-4 (AQP4) [...] Read more.
Extracellular vesicles (EVs) secreted by astrocytes (ADEVs) mediate numerous biological processes, providing insights into damage, repair, and protection following ischemic stroke (IS). This pilot study aimed to broaden the current knowledge on the astrocyte response to ischemia by dynamically assessing the aquaporin-4 (AQP4) and glial cell line-derived neurotrophic factor (GDNF) as cargo proteins of these vesicles in eighteen acute IS patients and nine controls. EV proteins were detected by Western blotting and followed 24 h (D1), 7 days (D7), and one month (M1) after symptoms onset. The post-ischemic ADEV AQP4 and GDNF levels were higher at D1 compared to the control group (p = 0.006 and p = 0.023). Significant differences were observed in ADEV AQP4 during the three evaluated time points (n = 12, p = 0.013) and between D1 and D7 (z = 2.858, p = 0.012), but not in EV GDNF. There was a positive relationship between the severity of stroke at D1 according to the National Institutes of Health Stroke Scale, and ADEV AQP4 at D1 (r = 0.50, p = 0.031), as well as ADEV GDNF at D1 and D7 (r = 0.49, p = 0.035 and r = 0.53, p = 0.021, respectively). The release of EVs with distinct protein profiles can be an attractive platform for the development of biomarkers in IS. Full article
(This article belongs to the Special Issue Molecular, Cellular, and Blood Biomarkers in Acute Ischemic Stroke)
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11 pages, 424 KiB  
Article
Association between Brain-Derived Neurotrophic Factor and Lipid Profiles in Acute Ischemic Stroke Patients
by Mayuri N. Tuwar, Wei-Hung Chen, Hsu-Ling Yeh and Chyi-Huey Bai
Int. J. Mol. Sci. 2024, 25(4), 2380; https://doi.org/10.3390/ijms25042380 - 17 Feb 2024
Cited by 1 | Viewed by 1159
Abstract
Ischemic stroke, the most prevalent form of stroke, leads to neurological impairment due to cerebral ischemia and affects 55–90% of the population. Brain-derived neurotrophic factor (BDNF) plays a crucial role in the central nervous system and regulates cardiometabolic risk factors, including lipids. This [...] Read more.
Ischemic stroke, the most prevalent form of stroke, leads to neurological impairment due to cerebral ischemia and affects 55–90% of the population. Brain-derived neurotrophic factor (BDNF) plays a crucial role in the central nervous system and regulates cardiometabolic risk factors, including lipids. This single-center study aimed to explore the relationship between lipid profiles and BDNF levels in 90 patients who had experienced AIS for the first time. The results show that the high BDNF group (≥3.227 ng/mL) had significantly higher HbA1C and TG levels; ratios of TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C; and percentage of hyperlipidemia (60%) as well as lower levels of HDL-C, with an OR of 1.903 (95% CI: 1.187–3.051) for TG/HDL-C, 1.975 (95% CI: 1.188–3.284) for TC/HDL-C, and 2.032 (95% CI: 1.113–3.711) for LDL-C/HDL-C. Plasma BDNF levels were found to be significantly positively correlated with TG and negatively with HDL-C, with OR values of 1.017 (95% CI: 1.003–1.030) and 0.926 (95% CI: 0.876–0.978), respectively. TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C ratios are associated with BDNF levels in AIS patients. The results also indicate that, in AIS patients, higher BDNF levels are associated with lower HDL and higher TG concentrations. Full article
(This article belongs to the Special Issue Molecular, Cellular, and Blood Biomarkers in Acute Ischemic Stroke)
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12 pages, 1207 KiB  
Article
The Prognostic Biomarkers of Plasma Trimethylamine N-Oxide and Short-Chain Fatty Acids for Recanalization Therapy in Acute Ischemic Stroke
by Ping-Song Chou, I-Hsiao Yang, Chia-Ming Kuo, Meng-Ni Wu, Tzu-Chao Lin, Yi-On Fong, Chi-Hung Juan and Chiou-Lian Lai
Int. J. Mol. Sci. 2023, 24(13), 10796; https://doi.org/10.3390/ijms241310796 - 28 Jun 2023
Cited by 3 | Viewed by 1738
Abstract
Bidirectional communication of the microbiota–gut–brain axis is crucial in stroke. Recanalization therapy, namely intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), are recommended for eligible patients with acute ischemic stroke (AIS). It remains unclear whether gut microbiota metabolites, namely trimethylamine N-oxide (TMAO) and short-chain [...] Read more.
Bidirectional communication of the microbiota–gut–brain axis is crucial in stroke. Recanalization therapy, namely intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), are recommended for eligible patients with acute ischemic stroke (AIS). It remains unclear whether gut microbiota metabolites, namely trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), can predict the prognosis after recanalization therapy. This prospective study recruited patients with AIS receiving IVT, EVT, or both. The National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores were used to assess the severity and functional outcomes of AIS, respectively. A functional outcome of mild-to-moderate disability was defined as a mRS score of 0–3 at discharge. Plasma TMAO and SCFA levels were measured through liquid chromatography with triple-quadrupole mass spectrometry. Fifty-six adults undergoing recanalization therapy for AIS were enrolled. Results showed that TMAO levels were not associated with stroke severity and functional outcomes, while isovalerate levels (one of the SCFAs) were negatively correlated with NIHSS scores at admission and discharge. In addition, high isovalerate levels were independently associated with a decreased likelihood of severe disability. The study concluded that an elevated plasma isovalerate level was correlated with mild stroke severity and disability after recanalization therapy for AIS. Full article
(This article belongs to the Special Issue Molecular, Cellular, and Blood Biomarkers in Acute Ischemic Stroke)
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Review

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25 pages, 1859 KiB  
Review
Unlocking the Potential of Stroke Blood Biomarkers: Early Diagnosis, Ischemic vs. Haemorrhagic Differentiation and Haemorrhagic Transformation Risk: A Comprehensive Review
by Lazzaro di Biase, Adriano Bonura, Pasquale Maria Pecoraro, Simona Paola Carbone and Vincenzo Di Lazzaro
Int. J. Mol. Sci. 2023, 24(14), 11545; https://doi.org/10.3390/ijms241411545 - 17 Jul 2023
Cited by 8 | Viewed by 4270
Abstract
Stroke, a complex and heterogeneous disease, is a leading cause of morbidity and mortality worldwide. The timely therapeutic intervention significantly impacts patient outcomes, but early stroke diagnosis is challenging due to the lack of specific diagnostic biomarkers. This review critically examines the literature [...] Read more.
Stroke, a complex and heterogeneous disease, is a leading cause of morbidity and mortality worldwide. The timely therapeutic intervention significantly impacts patient outcomes, but early stroke diagnosis is challenging due to the lack of specific diagnostic biomarkers. This review critically examines the literature for potential biomarkers that may aid in early diagnosis, differentiation between ischemic and hemorrhagic stroke, and prediction of hemorrhagic transformation in ischemic stroke. After a thorough analysis, four promising biomarkers were identified: Antithrombin III (ATIII), fibrinogen, and ischemia-modified albumin (IMA) for diagnostic purposes; glial fibrillary acidic protein (GFAP), micro RNA 124-3p, and a panel of 11 metabolites for distinguishing between ischemic and hemorrhagic stroke; and matrix metalloproteinase-9 (MMP-9), s100b, and interleukin 33 for predicting hemorrhagic transformation. We propose a biomarker panel integrating these markers, each reflecting different pathophysiological stages of stroke, that could significantly improve stroke patients’ early detection and treatment. Despite promising results, further research and validation are needed to demonstrate the clinical utility of this proposed panel for routine stroke treatment. Full article
(This article belongs to the Special Issue Molecular, Cellular, and Blood Biomarkers in Acute Ischemic Stroke)
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