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Recent advances in the structure and activation mechanisms of metabolite-releasing Pannexin 1 channels
Biochem Soc Trans. 2023 Aug 25:BST20230038. doi: 10.1042/BST20230038. Online ahead of print.ABSTRACTPannexin 1 (PANX1) is a widely expressed large-pore ion channel located in the plasma membrane of almost all vertebrate cells. It possesses a unique ability to act as a conduit for both inorganic ions (e.g. potassium or chloride) and bioactive metabolites (e.g. ATP or glutamate), thereby activating varying signaling pathways in an autocrine or paracrine manner. Given its crucial role in cell-cell interactions, the activity of PANX1 has been implicated in maintaining homeostasis of cardiovascular, immune, and nervous systems....
Source: Biochemical Society Transactions - August 25, 2023 Category: Biochemistry Authors: Yi-Ling Wu Ai-Hsing Yang Yu-Hsin Chiu Source Type: research

Differential effect of gold nanoparticles on cerebrovascular function and biomechanical properties
This study provides the first evidence that GNPs affect the structure and function of the cerebrovasculature, which may be important for their development and use in biomedical applications.
Source: Physiological Reports - August 22, 2023 Category: Physiology Authors: Ryan D. Hunt, Omid Sedighi, Wayne M. Clark, Amber L. Doiron, Marilyn  J. Cipolla Tags: ORIGINAL ARTICLE Source Type: research

Exosomal circCNOT6L Regulates Astrocyte Apoptotic Signals Induced by Hypoxia Exposure Through miR99a-5p/SERPINE1 and Alleviates Ischemic Stroke Injury
In conclusion, CircCNOT6L attenuated the cell apopt otic signal of astrocytes via the miR99a-5p/SERPINE1 axis and then alleviated injury after hypoxia induced by ischemic stroke.
Source: Molecular Neurobiology - August 2, 2023 Category: Neurology Source Type: research

Distinct Alterations in Oxygenation, Ion Composition and Acid-Base Balance in Cerebral Collaterals During Large-Vessel Occlusion Stroke
ConclusionThese findings suggest that stroke-induced changes in oxygen supply, ion composition and acid-base balance occur and dynamically progress within penumbral areas during human cerebral ischemia and are related to acute tissue damage.
Source: Klinische Neuroradiologie - June 7, 2023 Category: Radiology Source Type: research

Repurposing the K < sub > Ca < /sub > 3.1 Blocker Senicapoc for Ischemic Stroke
Transl Stroke Res. 2023 Apr 24. doi: 10.1007/s12975-023-01152-6. Online ahead of print.ABSTRACTSenicapoc, a small molecule inhibitor of the calcium-activated potassium channel KCa3.1, was safe and well-tolerated in clinical trials for sickle cell anemia. We previously reported proof-of-concept data suggesting that both pharmacological inhibition and genetic deletion of KCa3.1 reduces infarction and improves neurologic recovery in rodents by attenuating neuroinflammation. Here we evaluated the potential of repurposing senicapoc for ischemic stroke. In cultured microglia, senicapoc inhibited KCa3.1 currents with an IC50 of 7...
Source: Cell Research - April 24, 2023 Category: Cytology Authors: Ruth D Lee Yi-Je Chen Hai M Nguyen Latika Singh Connor J Dietrich Benjamin R Pyles Yanjun Cui Jonathan R Weinstein Heike Wulff Source Type: research

Repurposing the KCa3.1 Blocker Senicapoc for Ischemic Stroke
AbstractSenicapoc, a small molecule inhibitor of the calcium-activated potassium channel KCa3.1, was safe and well-tolerated in clinical trials for sickle cell anemia. We previously reported proof-of-concept data suggesting that both pharmacological inhibition and genetic deletion of KCa3.1 reduces infarction and improves neurologic recovery in rodents by attenuating neuroinflammation. Here we evaluated the potential of repurposing senicapoc for ischemic stroke. In cultured microglia, senicapoc inhibited KCa3.1 currents with an IC50 of 7  nM, reduced Ca2+ signaling induced by the purinergic agonist ATP, suppressed express...
Source: Translational Stroke Research - April 24, 2023 Category: Neurology Source Type: research

Discovery of a brain-sparing GIRK1/4 inhibitor for pharmacological cardioversion of atrial fibrillation
Bioorg Med Chem Lett. 2023 Mar 15;85:129237. doi: 10.1016/j.bmcl.2023.129237. Online ahead of print.ABSTRACTAtrial fibrillation (AF) is the most common cardiac arrhythmia, and a significant risk factor for ischemic stroke and heart failure. Marketed anti-arrhythmic drugs can restore sinus rhythm, but with limited efficacy and significant toxicities, including potential to induce ventricular arrhythmia. Atrial-selective ion channel drugs are expected to restore and maintain sinus rhythm without risk of ventricular arrhythmia. One such atrial-selective channel target is GIRK1/4 (G-protein regulated inwardly rectifying potass...
Source: Bioorganic and Medicinal Chemistry Letters - March 16, 2023 Category: Chemistry Authors: Stefan Peukert Hatice Belgin Gulgeze Efthymiou Ruowei Mo Yunshan Peng Fupeng Ma Guillaume Barbe Gregory Bebernitz Cary Fridrich Chiara Buono Eric T Williams Thomas Daniels Lisha Li Xia Zhang Yuichiro Adachi Mie Abe Andrew K P Taggart Source Type: research

Electrolyte Imbalance and Neurologic Injury
CNS Neurol Disord Drug Targets. 2023 Feb 15. doi: 10.2174/1871527322666230215144649. Online ahead of print.ABSTRACTNeurologic injury continues to be a debilitating worldwide disease with high morbidity and mortality. The systemic sequelae of a neural insult often lead to prolonged hospital stays and challenging nutritional demands that contribute to poorer prognoses. Clinical management of a given condition should prioritize preserving the homeostatic parameters disrupted by inflammatory response cascades following the primary insult. This focused review examines the reciprocal relationship between electrolyte disturbance ...
Source: CNS and Neurological Disorders Drug Targets - February 15, 2023 Category: Drugs & Pharmacology Authors: Jordan Poe Sai Sriram Yusuf Mehkri Brandon Lucke-Wold Source Type: research

Novel predictors and a predictive model of cerebrovascular atherosclerotic ischemic stroke based on clinical databases
CONCLUSION: The efficacy of the predictive model was acceptable as an aid in predicting cerebrovascular atherosclerotic ischemic stroke.PMID:36413433 | DOI:10.1080/01616412.2022.2149185
Source: Atherosclerosis - November 22, 2022 Category: Cardiology Authors: He Li Pei Liu Hong-Yu Ma Wei-Long Hua Yong-Xin Zhang Lei Zhang Yong-Wei Zhang Bo Hong Peng-Fei Yang Jian-Min Liu Source Type: research

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