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Iodine and the Body

Iodide and Brain (CNS)

• Adams
• Ahmed
• Andrasi
• Becker
• Bernal
• Bito
• Cao, DeLong, Jiang
• Cserr
• Cunnane
• Cutler, Hammerstad
• Escobar
• Fayen
• Gabrichidze
• Hetzel
• Mastorakos
• McCarrison
• Mitchell
• Peeters
• Rao
• Sethi
• Thiel
• Unal-Cevik
• Visser
• Woodbury
• Yin

Unal-Cevik

Apoptotic and necrotic death mechanisms are concomitantly activated in the same cell after cerebral ischemia.

Unal-Cevik I, Kilinc M, Can A, Gursoy-Ozdemir Y, Dalkara T.

Stroke. 2004 Sep;35(9):2189-94. Epub 2004 Jul 15.

"BACKGROUND AND PURPOSE: Both necrotic and apoptotic cell death mechanisms are activated after cerebral ischemia. However, whether they are concomitantly active in the same cell or in discrete cell populations is not known.

METHODS: We investigated activation of both pathways at the cellular level in mice brains subjected to transient or permanent focal ischemia.

RESULTS: Four hours after ischemia, diffuse cathepsin-B spillage into cytoplasm, suggesting lysosomal leakage, was observed within neurons immunoreactive for the active form of caspase-3 (p20). Ischemic neurons with a leaky plasma membrane (positive for propidium iodide) were colabeled with caspase-cleaved actin fragment and exhibited TUNEL-positive nuclei having apoptotic morphology. At 72 hours, up to 27% of cells with caspase activity displayed morphological features suggestive of secondary necrosis.

CONCLUSIONS: These data, demonstrating an early and concurrent increase in caspase-3 and cathepsin-B activities followed by appearance of caspase-cleavage products, DNA fragmentation, and membrane disintegration, suggest that subroutines of necrotic and apoptotic cell death are concomitantly activated in ischemic neurons and that the dominant cell death phenotype is determined by the relative speed of each process."

Intravenously administered propidium iodide labels necrotic cells in the intact mouse brain after injury.

Unal-Cevik I, Dalkara T.

Cell Death Differ. 2003 Aug;10(8):928-9.

"Apoptosis and necrosis have been identified as two morphologically distinct types of cell death. However, under some conditions, the same cell may display both apoptotic and necrotic features. Although several markers of both pathways are available to study the complex nature of cell death in vitro, the markers that can be used in vivo (especially in the brain) are limited. Since loss of membrane integrity is a pathognomonic feature of necrotic cell death, adapting techniques using membrane-impermeant dyes such as propidium iodide (PI) to in vivo conditions may help investigating mechanisms of cell death in vivo."

"In conclusion, PI can safely be used as a marker of disrupted plasma membrane integrity of necrotic cells under in vivo conditions after i.v. as well as i.c.v. administration. The i.v. administration is technically simple and gives acceptably intense fluorescent signals to detect the necrotic cells in brain. However, it requires the presence of a leaky BBB and prolonged postinjection survival times to reach sufficiently high levels in the injured cells."

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