{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:46:24Z","timestamp":1791996384333,"version":"4.4.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>JOURNAL\/nrgr\/04.03\/01300535-202502000-00027\/figure1\/v\/2026-05-04T143158Z\/r\/image-tiff<\/jats:p>\n                  <jats:p>Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia\/reperfusion injury. Low-density lipoprotein receptor, a classic cholesterol regulatory receptor, has been found to inhibit NLR family pyrin domain containing protein 3 (NLRP3) inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer\u2019s disease. However, little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke. To address this issue in the present study, we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models. First, we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis. We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen\u2013glucose deprivation\/reoxygenation. Second, we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus. Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype. Finally, we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen\u2013glucose deprivation\/reoxygenation injured astrocytes and that the addition of nigericin, an NLRP3 agonist, restored the neurotoxic astrocyte phenotype. These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.<\/jats:p>","DOI":"10.4103\/nrr.nrr-d-23-01263","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T03:00:11Z","timestamp":1717642811000},"page":"491-502","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke"],"prefix":"10.4103","volume":"20","author":[{"given":"Shuai","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, 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Nanjing, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junshan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8630-2586","authenticated-orcid":false,"given":"Hongdong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, 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