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Although the classical core\u2013penumbra framework captures general relationships between perfusion severity and tissue viability, it fails to explain this marked inter-individual heterogeneity under comparable ischemic stress. We recently established the nitric oxide synthase inhibitor-mediated large artery ischemic stroke model (NAIM), which converts unilateral carotid occlusion from a typically benign oligemic state into a high-incidence yet non-deterministic infarction paradigm. In this review, we present NAIM as a mechanistically defined platform for investigating infarction occurrence as a threshold-driven process spanning vascular, metabolic, and microcirculatory scales. Using a large-scale NAIM dataset (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u2009900 mice) from our recent study, we reappraise the original findings and extend the analysis to post-hoc observations not addressed in the initial report. Finally, integrating these experimental insights with clinical and basic investigations from our group and the broader literature, we outline how ischemic outcome (tissue survival vs infarction) emerges from a threshold-sensitive nonlinear system defined by collateral anatomy; macro-\/micro-vascular integrity; and systemic, metabolic, and genetic modifiers.\n                  <\/jats:p>","DOI":"10.1177\/0271678x261447117","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T06:09:37Z","timestamp":1779170977000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Occurrence of cerebral infarction, a threshold-sensitive nonlinear process: Lessons from a new stroke model, NAIM"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9473-5152","authenticated-orcid":false,"given":"Jinyong","family":"Chung","sequence":"first","affiliation":[{"name":"Medical Science Research Center, Dongguk University, Goyang, South Korea"},{"name":"National Priority Research Center for Stroke, Goyang, South Korea"},{"name":"Department of Medical Engineering, Dongguk University College of Medicine, Goyang, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7850-0804","authenticated-orcid":false,"given":"Dong-Seok","family":"Gwak","sequence":"additional","affiliation":[{"name":"National Priority Research Center for Stroke, Goyang, South Korea"},{"name":"Department of Neurology, Dongguk University Ilsan Hospital, Goyang, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2719-3012","authenticated-orcid":false,"given":"Beom Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Eog","family":"Kim","sequence":"additional","affiliation":[{"name":"Medical Science Research Center, Dongguk University, Goyang, South Korea"},{"name":"National Priority Research Center for Stroke, Goyang, South Korea"},{"name":"Department of Neurology, Dongguk University Ilsan Hospital, Goyang, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.124.049496"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000578"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70291-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30506-2"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0058-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2015.17.3.320"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.124.049013"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2022.02936"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000086465.41263.06"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2007.132100"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.038085"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2011.93"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14916"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00027.2014"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-022-01090-9"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2333"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2399"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06440-3"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.104132"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.10"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-018-0626-y"},{"key":"e_1_3_2_23_2","article-title":"Genetic determinants of insufficiency of the collateral circulation","volume":"2025","author":"Faber JE.","year":"2025","unstructured":"Faber JE. 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