Purinergic signaling: a potential therapeutic target for ischemic stroke

Wang, Lu; Li, Yingjie; Xu, Yang; Yang, Bo; Zhang, Xin; Zhang, Jing; Zhang, Qi; Cheng, Xu-Dong; Wang, Jianhong; Yu, Neng-Wei

doi:10.1007/s11302-022-09905-y

Cited by 7 publications

(6 citation statements)

References 79 publications

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“…Thrombus formation is a complex interplay of various immuno-inflammatory molecules and signaling pathways [ 30 – 35 ]. As a result, certain immunoinflammatory mediators show promise for identifying the source of thrombus.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of Semaphorin-7A /CD163-positive macrophages in large artery and cardiogenic stroke

Jiang,

Sun,

et al. 2024

BMC Neurol

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Background Identification of the causes of stroke of undetermined etiology, specifically cardioembolism (CE) and non-CE causes, can inform treatment planning and prognosis prediction. The objective of this study was to analyze the disparities in thrombus composition, particularly Semaphorin-7A (Sema7A) and CD163, between patients diagnosed with large-artery atherosclerosis (LAA) and those with CE, and to investigate their potential association with prognosis. Methods Thrombi were collected from patients who underwent mechanical thrombectomy at two hospitals. The patients were categorized into two groups: LAA and CE. We compared the levels of Sema7A and CD163 between these groups and analyzed their relationships with stroke severity, hemorrhagic transformation and prognosis. Results The study involved a total of 67 patients. Sema7A expression was found to be significantly higher in the CE group compared to LAA (p < 0.001). Conversely, no statistically significant differences were observed for CD163 between the groups. The presence of Sema7A/CD163 did not show any associations with stroke severity or hemorrhagic transformation (all p > 0.05). However, both Sema7A (OR, 2.017; 95% CI, 1.301–3.518; p = 0.005) and CD163 (OR, 2.283; 95% CI, 1.252–5.724; p = 0.03) were associated with the poor prognosis for stroke, after adjusting for stroke severity. Conclusion This study highlights that CE thrombi exhibited higher levels of Sema7A expression compared to LAA thrombi. Moreover, we found a positive correlation between Sema7A/CD163 levels and the poor prognosis of patients with acute ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Differential expression of Semaphorin-7A /CD163-positive macrophages in large artery and cardiogenic stroke

Jiang,

Sun,

et al. 2024

BMC Neurol

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“…Cell surface expression of anticoagulant molecules including heparan sulfate proteoglycan and thrombomodulin also limit the thrombotic process [45] by interfering with thrombin generation and fibrin formation. Antiplatelet ectonucleotidases are associated with endothelial cells, including CD39 and CD73, and prevent nucleotide induced activation of platelets [49]. When the continuity of the endothelial layer is disrupted by injury (Figure 2, top), the underlining extracellular matrix is exposed to flowing blood leading to platelet recruitment, adhesion, and aggregation resulting in formation of the primary hemostatic plug [50].…”

Section: Thrombosis Is a Multifaceted Processmentioning

confidence: 99%

“…Antioxidants 2024, 13, x FOR PEER REVIEW 5 o induced activation of platelets [49]. When the continuity of the endothelial layer is rupted by injury (Figure 2, top), the underlining extracellular matrix is exposed to flow blood leading to platelet recruitment, adhesion, and aggregation resulting in formatio the primary hemostatic plug [50].…”

Section: Thrombosis Is a Multifaceted Processmentioning

confidence: 99%

Targeting Cysteine Oxidation in Thrombotic Disorders

Yang,

Silverstein

2024

Antioxidants

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Oxidative stress increases the risk for clinically significant thrombotic events, yet the mechanisms by which oxidants become prothrombotic are unclear. In this review, we provide an overview of cysteine reactivity and oxidation. We then highlight recent findings on cysteine oxidation events in oxidative stress-related thrombosis. Special emphasis is on the signaling pathway induced by a platelet membrane protein, CD36, in dyslipidemia, and by protein disulfide isomerase (PDI), a member of the thiol oxidoreductase family of proteins. Antioxidative and chemical biology approaches to target cysteine are discussed. Lastly, the knowledge gaps in the field are highlighted as they relate to understanding how oxidative cysteine modification might be targeted to limit thrombosis.

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“…Purines have emerged as a leading class of neuromodulatory signaling molecules involved in a host of protective and regenerative functions both during and following ischemic attack. − Both ATP and GTP are well known for their roles in neurotransmission and intercellular communication, − but their nucleoside counterparts have emerged as increasingly important regulatory molecules active at the point of assault. Adenosine’s role, as both a rapid and a chronic protective agent, has been well characterized in recent years. − However, its sister molecule guanosine remains far less understood but increasingly appears to play a central role in neuroprotection during ischemic attack.…”

Section: Introductionmentioning

confidence: 99%

Dynamic and Rapid Detection of Guanosine during Ischemia

Weese-Myers

Cryan

Witt

et al. 2023

ACS Chem. Neurosci.

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Guanosine acts in both neuroprotective and neurosignaling pathways in the central nervous system; in this paper, we present the first fast voltammetric measurements of endogenous guanosine release during pre-and post-ischemic conditions. We discuss the metric of our measurements via analysis of event concentration, duration, and interevent time of rapid guanosine release. We observe changes across all three metrics from our normoxic to ischemic conditions. Pharmacological studies were performed to confirm that guanosine release is a calcium-dependent process and that the signaling observed is purinergic. Finally, we show the validity of our ischemic model via staining and fluorescent imaging. Overall, this paper sets the tone for rapid monitoring of guanosine and provides a platform to investigate the extent to which guanosine accumulates at the site of brain injury, i.e., ischemia.

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Purinergic signaling: a potential therapeutic target for ischemic stroke

Cited by 7 publications

References 79 publications

Differential expression of Semaphorin-7A /CD163-positive macrophages in large artery and cardiogenic stroke

Differential expression of Semaphorin-7A /CD163-positive macrophages in large artery and cardiogenic stroke

Targeting Cysteine Oxidation in Thrombotic Disorders

Dynamic and Rapid Detection of Guanosine during Ischemia

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