{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:02:41Z","timestamp":1777914161859,"version":"3.51.4"},"reference-count":43,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>Nonclinical studies of test articles (TAs) in nonhuman primates are often designed to assess both biodistribution and toxicity. For this purpose, studies commonly use intravenous perfusion of ice-cold (2\u00b0C-8\u00b0C) saline to facilitate measurements of TA-associated nucleic acids and proteins, after which tissues undergo later fixation by immersion for histological processing and microscopic evaluation. Intriguingly, minimal apoptosis\/single cell necrosis (A\/SCN) of randomly distributed neural cells is evident in the cerebral cortex and less often the hippocampus in animals from all groups, including vehicle-treated controls. Affected cells exhibit end-stage features such as cytoplasmic hypereosinophilia, nuclear condensation or fragmentation, and shape distortions, so their lineage(s) generally cannot be defined; classical apoptotic bodies are exceedingly rare. In addition, A\/SCN is not accompanied by glial reactions, leukocyte infiltration\/inflammation, or other parenchymal changes. The severity is minimal in controls but may be slightly exacerbated (to mild) by TA that accumulate in neural cells. One plausible hypothesis explaining this A\/SCN exacerbation is that cold shock (perhaps complicated by concurrent tissue acidity and hypoxia) drives still-viable but TA-stressed cells to launch a self-directed death program. Taken together, these observations indicate that A\/SCN in brain processed by cold saline perfusion with delayed immersion fixation represents a procedural artifact and not a TA-related lesion.<\/jats:p>","DOI":"10.1177\/01926233241247044","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T07:28:20Z","timestamp":1714030100000},"page":"343-349","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Toxicologic Pathology Forum: Apoptosis\/Single Cell Necrosis as a Possible Procedural Effect in Primate Brain Following Ice-Cold Saline Perfusion"],"prefix":"10.1177","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-1492","authenticated-orcid":false,"given":"Brad","family":"Bolon","sequence":"first","affiliation":[{"name":"GEMpath Inc., Longmont, CO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8653-9167","authenticated-orcid":false,"given":"Joy M.","family":"Gary","sequence":"additional","affiliation":[{"name":"StageBio, Frederick, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"key":"bibr1-01926233241247044","doi-asserted-by":"publisher","DOI":"10.1177\/01926233221101314"},{"key":"bibr2-01926233241247044","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-165X.1992.tb00576.x"},{"key":"bibr3-01926233241247044","doi-asserted-by":"publisher","DOI":"10.1177\/0192623317749453"},{"key":"bibr4-01926233241247044","doi-asserted-by":"publisher","DOI":"10.1177\/0192623317720120"},{"key":"bibr5-01926233241247044","doi-asserted-by":"publisher","DOI":"10.1177\/0192623310385145"},{"key":"bibr6-01926233241247044","doi-asserted-by":"publisher","DOI":"10.1177\/0192623319861364"},{"key":"bibr7-01926233241247044","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385157-4.00589-3"},{"key":"bibr8-01926233241247044","doi-asserted-by":"publisher","DOI":"10.1177\/0192623312474865"},{"key":"bibr9-01926233241247044","doi-asserted-by":"publisher","DOI":"10.1177\/0192623318772484"},{"key":"bibr10-01926233241247044","doi-asserted-by":"publisher","DOI":"10.1177\/0192623320951154"},{"key":"bibr11-01926233241247044","doi-asserted-by":"publisher","DOI":"10.1293\/tox.34.183S"},{"key":"bibr12-01926233241247044","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.672526"},{"key":"bibr13-01926233241247044","volume":"34","author":"Colman K","year":"2021","journal-title":"(M. fascicularis). 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