{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:41:02Z","timestamp":1773308462092,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,5,13]],"date-time":"2003-05-13T00:00:00Z","timestamp":1052784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Blockade of mitochondrial permeability transition protects against hypoglycemic brain damage. To study the mechanisms downstream from mitochondria that may cause neuronal death, we investigated the effects of cyclosporin A on subcellular localization of apoptosis\u2010inducing factor and cytochrome\u2003<jats:italic>c<\/jats:italic>, activation of the cysteine proteases calpain and caspase\u20103, as well as its effect on brain extracellular calcium concentrations. Redistribution of cytochrome\u2003<jats:italic>c<\/jats:italic> occurred at 30\u2003min of iso\u2010electricity, whereas translocation of apoptosis\u2010inducing factor to nuclei occurred at 30\u2003min of recovery following 30\u2003min of iso\u2010electricity. Active caspase\u20103 and calpain\u2010induced fodrin breakdown products were barely detectable in the dentate gyrus and CA1 region of the hippocampus of rat brain exposed to 30 or 60\u2003min of insulin\u2010induced hypoglycemia. However, 30\u2003min or 3\u2003h after recovery of blood glucose levels, fodrin breakdown products and active caspase\u20103 markedly increased, concomitant with a twofold increase in caspase\u20103\u2010like enzymatic activity. When rats were treated with neuroprotective doses of cyclosporin A, but not with FK 506, the redistribution of apoptosis\u2010inducing factor and cytochrome\u2003<jats:italic>c<\/jats:italic> was reduced and fodrin breakdown products and active caspase\u20103 immuno\u2010reactivity was diminished whereas the extracellular calcium concentration was unaffected. We conclude that hypoglycemia leads to mitochondrial permeability transition which, upon recovery of energy metabolism, mediates the activation of caspase\u20103 and calpains, promoting cell death.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2003.01794.x","type":"journal-article","created":{"date-parts":[[2003,6,3]],"date-time":"2003-06-03T10:18:04Z","timestamp":1054635484000},"page":"1431-1442","source":"Crossref","is-referenced-by-count":72,"title":["Cyclosporin A prevents calpain activation despite increased intracellular calcium concentrations, as well as translocation of apoptosis\u2010inducing factor, cytochrome\u2003<i>c<\/i> and caspase\u20103 activation in neurons exposed to transient hypoglycemia"],"prefix":"10.1111","volume":"85","author":[{"given":"Michel","family":"Ferrand\u2010Drake","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changlian","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunilla","family":"Gid\u00f6","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anker J.","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan\u2010Olof","family":"Karlsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"A. 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