α7 nicotinic acetylcholine receptor agonist improved brain injury and impaired glucose metabolism in a rat model of ischemic stroke

Wang, Yayu; Lin, Shih‐Yi; Chang, Chieh-Ming J.; Wu, Chih-Cheng; Chen, Wenying; Huang, Wei-Chi; Liao, Su‐Lan; Wang, Wenyi; Chen, Chun-Jung

doi:10.1007/s11011-023-01167-w

Cited by 6 publications

(2 citation statements)

References 47 publications

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“…Since angiogenesis can be detrimental in atherosclerosis, it is not yet clear how 7nAChR imaging in this context should be interpreted [5,29]. Several preclinical studies have demonstrated the therapeutic potential of 7nAChR stimulation following stroke [30][31][32]. While 7nAChR imaging has not yet been included, one study utilised radiotracers for in ammation ([ 18 F]DPA-714) and matrix metalloprotease (MMP) [32].…”

Section: Discussionmentioning

confidence: 99%

Assessment of the alpha 7 nicotinic acetylcholine receptor as an imaging marker of cardiac repair-associated processes using NS14490

Reid,

McLoughlin,

Stott

et al. 2023

Preprint

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Background Cardiac repair and remodeling following myocardial infarction (MI) is a multifactorial process involving pro-reparative inflammation, angiogenesis and fibrosis. Non-invasive imaging using a radiotracer targeting these processes could provide a key research tool to understand the underlying mechanisms in cardiac wound healing. Activation of the alpha7 nicotinic acetylcholine receptor (ɑ7nAChR) stimulates pro-reparative macrophage activity and angiogenesis. We investigated whether this target could serve as an imaging biomarker for these interlinked wound healing responses by assessing in vitro cellular expression and by using a tritiated-version of the PET radiotracer [18F]NS14490 in tissue autoradiography studies. Results ɑ7nAChR expression in monocyte-derived macrophages and vascular cells showed the highest relative expression was within macrophages, but only endothelial cells exhibited a proliferation and hypoxia driven increase in expression. Using a mouse model of inflammatory angiogenesis following sponge implantation, specific binding of [3H]NS14490 increased from 3.6 ± 0.2 µCi/g at day 3 post-implantation to 4.9 ± 0.2 µCi/g at day 7 (n = 4, p < 0.01), followed by a reduction in specific binding at days 14 and 21. This peak matched the onset of vessel formation and macrophage infiltration. In a rat MI model, specific binding of [3H]NS14490 was low within the myocardium of the sham cohort and the remote myocardium of the MI cohort. Specific binding within the infarcted myocardium increased from day 14 post-MI (33.8 ± 14.1 µCi/g, P ≤ 0.01 versus sham), peaking at day 28 (48.9 ± 5.1 µCi/g, P ≤ 0.0001 versus sham). Histological and proteomic profiling of ɑ7nAChR positive MI tissue revealed strong associations between the ɑ7nAChR signal and extracellular matrix deposition. Conclusion ɑ7nAChR is highly expressed in macrophages and showed proliferation and hypoxia driven expression in endothelial cells. While NS14490 imaging displays a pattern that coincides with vessel formation and macrophage infiltration in the sponge model, this is not the case in the MI model where the ɑ7nAChR signal strongly associated with extracellular matrix deposition. Overall, these findings support the involvement of ɑ7nAChR across several processes central to cardiac repair and warrant further investigation to assess the role of ɑ7nAChR in fibrosis and establish the relationship with cardiac function during adverse remodelling.

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Section: Discussionmentioning

confidence: 99%

Assessment of the alpha 7 nicotinic acetylcholine receptor as an imaging marker of cardiac repair-associated processes using NS14490

Reid,

McLoughlin,

Stott

et al. 2023

Preprint

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“…Glucose serves as the primary energy source for neurons and astrocytes, while lactate provides supplementary energy for neurons. Disruptions in energy metabolism, along with oxidative stress and mitochondrial dysfunction, worsen brain injury after ischemia [ 118 ]. Abnormal glucose metabolism is a well-established pathological mechanism of IS.…”

Section: Research On the Mechanism Of Metabolic Damage To Ismentioning

confidence: 99%

Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke

Wei,

Chen,

Deng

et al. 2024

Biomark Res

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Ischemic stroke (IS), a devastating cerebrovascular accident, presents with high mortality and morbidity. Following IS onset, a cascade of pathological changes, including excitotoxicity, inflammatory damage, and blood-brain barrier disruption, significantly impacts prognosis. However, current clinical practices struggle with early diagnosis and identifying these alterations. Metabolomics, a powerful tool in systems biology, offers a promising avenue for uncovering early diagnostic biomarkers for IS. By analyzing dynamic metabolic profiles, metabolomics can not only aid in identifying early IS biomarkers but also evaluate Traditional Chinese Medicine (TCM) efficacy and explore its mechanisms of action in IS treatment. Animal studies demonstrate that TCM interventions modulate specific metabolite levels, potentially reflecting their therapeutic effects. Identifying relevant metabolites in cerebral ischemia patients holds immense potential for early diagnosis and improved outcomes. This review focuses on recent metabolomic discoveries of potential early diagnostic biomarkers for IS. We explore variations in metabolites observed across different ages, genders, disease severity, and stages. Additionally, the review examines how specific TCM extracts influence IS development through metabolic changes, potentially revealing their mechanisms of action. Finally, we emphasize the importance of integrating metabolomics with other omics approaches for a comprehensive understanding of IS pathophysiology and TCM efficacy, paving the way for precision medicine in IS management.

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Aronia Melanocarpa Elliot Anthocyanins Inhibits Alcoholic Liver Disease by Activation of α7nAChR

Wei,

Tang,

et al. 2024

Plant Foods Hum Nutr

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α7 nicotinic acetylcholine receptor agonist improved brain injury and impaired glucose metabolism in a rat model of ischemic stroke

Cited by 6 publications

References 47 publications

Assessment of the alpha 7 nicotinic acetylcholine receptor as an imaging marker of cardiac repair-associated processes using NS14490

Assessment of the alpha 7 nicotinic acetylcholine receptor as an imaging marker of cardiac repair-associated processes using NS14490

Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke

Aronia Melanocarpa Elliot Anthocyanins Inhibits Alcoholic Liver Disease by Activation of α7nAChR

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