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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

Reinventing the Penumbra — the Emerging Clockwork of a Multi-modal Mechanistic Paradigm
AbstractThe concept of the ischemic penumbra was originally defined as the area around a necrotic stroke core and seen as the tissue at imminent risk of further damage. Today, the penumbra is generally considered as time-sensitive hypoperfused brain tissue with decreased oxygen and glucose availability, salvageable tissue as treated by intervention, and the potential target for neuroprotection in focal stroke. The original concept entailed electrical failure and potassium release but one short of neuronal cell death and was based on experimental stroke models, later confirmed in clinical imaging studies. However, even thou...
Source: Translational Stroke Research - October 11, 2022 Category: Neurology Source Type: research