{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:39:02Z","timestamp":1783075142978,"version":"3.54.6"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Ischemic strokes contribute significantly to cardiovascular-related deaths in the U.S., with current interventions limited to thrombolytic agents. However, these agents present challenges such as a limited therapeutic window, incomplete reperfusion rates, risk of transformation, reperfusion-induced inflammation, and a lack of promoting neuroprotection. We investigated an additional strategy in which prior studies indicated a neuroprotective role. Using a murine transient middle cerebral artery occlusion (tMCAO) model, we sought to evaluate the neurotherapeutic efficacy of a positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor (\u03b17-nAChR), PNU-120596 (PNU), specifically examining whether PNU would modulate stroke-induced neurological dysfunction and neuropathology, with modulation of neuroinflammation as a possible mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Young male C57BL\/6J mice received a subcutaneous injection of 20mg\/kg of vehicle (DMSO) or PNU-120596 immediately after reperfusion, and infarct area and Bederson score were analyzed 24 hours post-stroke. In the 72-hour post-stroke study, the animals were injected with 20mg\/kg of PNU or vehicle subcutaneously immediately after reperfusion, followed by two additional doses of 10mg\/kg of PNU or vehicle at 24 and 48 hours post-tMCAO. Seventy-two hours later, behavior function and infarct area were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In contrast to previous rat studies that demonstrated improvements in clinical outcomes, a single administration of PNU following stroke induction led to a reduction in acute neuropathology but did not produce a significant improvement in motor outcomes. Prolonged treatment showed no significant changes in acute neuropathology or sensorimotor function. Additionally, an assessment of neuroinflammation revealed no changes in CD4 T-cell cellularity or phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings, alongside prior studies, suggest that the therapeutic efficacy of PNU may be contingent upon the timing of administration, dosage, and pharmacokinetics.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2025.1525975","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T07:26:30Z","timestamp":1739345190000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The efficacy of an allosteric modulator of the alpha 7 nicotinic acetylcholine receptor in a murine model of stroke"],"prefix":"10.3389","volume":"19","author":[{"given":"Katherine","family":"Hernandez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling B.","family":"Ortega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1161\/circresaha.116.309278","article-title":"Acute ischemic stroke therapy overview.","volume":"120","author":"Catanese","year":"2017","journal-title":"Circ. 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