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Microsurgical decompression effectively stabilizes primary anatomy. However, it often fails to stop the complex biochemical cascades of secondary neurodegeneration. There is a critical need to bridge the gap between anatomical preservation and functional recovery. Strong preclinical evidence indicates that delayed bioenergetic failure within the injury microenvironment heavily dictates long-term outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Advances:<\/jats:title>\n                    <jats:p>We synthesize the ARFE (autophagy-reactive oxygen species-ferroptosis-edema) axis as a mechanistic framework delineating the pathological continuum from subcellular failure to macroscopic tissue edema. In this irreversible cascade, adenosine triphosphate depletion blocks autophagic flux, forcing ferritinophagy-driven iron release and lipid peroxidation, while succinate accumulation locks microglia in metabolic collapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Critical Issues:<\/jats:title>\n                    <jats:p>A translational gap persists because mechanical hematoma evacuation does not inherently reverse the metabolic cascades driving secondary injury. Current single-target modalities fail because they do not account for the evolving metabolic microenvironment, leading to unchecked inflammation and cell death despite successful surgical intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Future Directions:<\/jats:title>\n                    <jats:p>\n                      We propose a paradigm shift from single-target modalities to \u201cspatiotemporal metabolic engineering.\u201d This strategy synchronizes interventions with metabolic logic. Hyperacute treatments focus on redox containment to neutralize iron. Acute phases prioritize immune-metabolic reprogramming for inflammation. Finally, subacute stages aim for bioenergetic reconstruction to support axonal regrowth.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      45, 397\u2013412.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261455615","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T09:08:41Z","timestamp":1780909721000},"page":"397-412","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Collapse in Acute CNS Injury: A Spatiotemporal Framework Linking Redox Failure, Ferroptosis, and Neurovascular Dysfunction"],"prefix":"10.1177","volume":"45","author":[{"given":"Liang","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China."},{"name":"Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury, Zhengzhou, Henan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China."},{"name":"Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury, Zhengzhou, Henan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China."},{"name":"Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury, Zhengzhou, Henan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiluo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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