{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:16:54Z","timestamp":1785763014547,"version":"3.56.0"},"reference-count":90,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Florida Heart Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Postoperative cognitive dysfunction (POCD) is a common disorder after general anesthesia in elderly patients, the precise mechanisms of which remain unclear. Methods: We investigated the effect of isoflurane with or without dantrolene pretreatment on intracellular calcium concentration ([Ca2+]i), reactive oxygen species (ROS) production, cellular lactate dehydrogenase (LDH) leak, calpain activity, and cognitive function using the Morris water maze test of young (3 months), middle-aged (12\u201313 months), and aged (24\u201325 months) C57BL6\/J mice. Results: Aged cortical and hippocampal neurons showed chronically elevated [Ca2+]i compared to young neurons. Furthermore, aged hippocampal neurons exhibited higher ROS production, increased LDH leak, and elevated calpain activity. Exposure to isoflurane exacerbated these markers in aged neurons, contributing to increased cognitive deficits in aged mice. Dantrolene pretreatment reduced [Ca2+]i for all age groups and prevented or significantly mitigated the effects of isoflurane on [Ca2+]i, ROS production, LDH leak, and calpain activity in aged neurons. Dantrolene also normalized or improved age-associated cognitive deficits and mitigated the cognitive deficits caused by isoflurane. Conclusions: These findings suggest that isoflurane-induced cytotoxicity and cognitive decline in aging are linked to disruptions in neuronal intracellular processes, highlighting the reduction of [Ca2+]i as a potential therapeutic intervention.<\/jats:p>","DOI":"10.3390\/cells13030264","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T09:41:59Z","timestamp":1706694119000},"page":"264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Post-Anesthesia Cognitive Dysfunction in Mice Is Associated with an Age-Related Increase in Neuronal Intracellular [Ca2+]\u2014Neuroprotective Effect of Reducing Intracellular [Ca2+]: In Vivo and In Vitro Studies"],"prefix":"10.3390","volume":"13","author":[{"given":"Arkady","family":"Uryash","sequence":"first","affiliation":[{"name":"Division of Neonatology, Mount Sinai Medical Center, Miami, FL 33140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Mijares","sequence":"additional","affiliation":[{"name":"Centro de Biof\u00edsica y Bioqu\u00edmica, Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos E.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy, Wellmax, Miami, FL 33314, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9401-2226","authenticated-orcid":false,"given":"Jose A.","family":"Adams","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Mount Sinai Medical Center, Miami, FL 33140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Allen","sequence":"additional","affiliation":[{"name":"Leeds Institute of Biomedical & Clinical Sciences, University of Leeds, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1211-2432","authenticated-orcid":false,"given":"Jose R.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0140-6736(55)92689-1","article-title":"Adverse cerebral effects of anaesthesia on old people","volume":"269","author":"Bedford","year":"1955","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s00540-009-0744-5","article-title":"Postoperative cognitive decline","volume":"23","author":"Sauer","year":"2009","journal-title":"J. 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