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Brain Res. 2003 Jan 17;960(1-2):62-70.

Calcium-induced mitochondrial swelling and cytochrome c release in the brain: its biochemical characteristics and implication in ischemic neuronal injury.

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Department of Neurosurgery, University of Hokkaido Graduate School of Medicine, North 15 West 7, Kita-ku, , Sapporo 060-8638, Japan.


The objective of the present study was to determine the biochemical characteristics of Ca(2+)-induced mitochondrial swelling (mitochondrial permeability transition; mPT) and cytochrome c release in the brain, and to clarify its role in neuronal injury following transient forebrain ischemia. Mitochondria were isolated from rat brain and liver. Changes in mitochondrial volume were measured via light absorbance at 540 nm. Using Western blot analysis, we examined the in vitro release of mitochondrial cytochrome c under these conditions. Transient forebrain ischemia was induced by 5 min occlusion of the common carotid arteries in the gerbil. Cyclosporin A (CsA), a specific mPT blocker, and/or trifluoperazine, a blocker of phospholipase A(2), were given before and 24 h after ischemia. The number of surviving neurons in the hippocampal CA1 sector was counted 7 days after ischemia. Calcium induced a moderate decrease of light absorbance in brain mitochondria, which was inhibited by CsA. However, calcium induced a much larger decrease of light absorbance in liver mitochondria. Calcium induced a moderate release of cytochrome c from brain mitochondria, which was not inhibited by CsA. However, calcium induced the release of a larger amount of cytochrome c from liver mitochondria. Selective neuronal injury due to transient forebrain ischemia was significantly ameliorated by treatment with high-dose CsA. The biochemical properties of Ca(2+)-induced mitochondrial swelling in the brain are different from those in the liver. Cytochrome c is released from brain mitochondria through an mPT-independent mechanism. CsA potentially ameliorates delayed neuronal injury in the hippocampus due to transient forebrain ischemia.

[Indexed for MEDLINE]

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