t  Mitochondrial Release of Cytochrome<i>c</i>Corresponds to the Selective Vulnerability of Hippocampal CA1 Neurons in Rats after Transient Global Cerebral Ischemia

Sugawara, Taku; Fujimura, Miki; Morita-Fujimura, Yuiko; Kawase, Makoto; Chan, Pak H.

doi:10.1523/jneurosci.19-22-j0002.1999

Cited by 210 publications

(218 citation statements)

References 28 publications

(45 reference statements)

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“…Two hours after OGD, the number of cytochrome c-immunopositive cells in area CA1 was significantly increased (Fig. 2), similar to results after cerebral ischemia in vivo (Sugawara et al, 1999). Diazepam, included in the reoxygenation buffer, completely prevented the OGD-induced increase in cytochrome c-immunopositive cells.…”

Section: Resultssupporting

confidence: 80%

Changes in Intracellular Chloride after Oxygen–Glucose Deprivation of the Adult Hippocampal Slice: Effect of Diazepam

Galeffi¹,

Sah²,

Pond³

et al. 2004

J. Neurosci.

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Section: Resultssupporting

confidence: 80%

Changes in Intracellular Chloride after Oxygen–Glucose Deprivation of the Adult Hippocampal Slice: Effect of Diazepam

Galeffi¹,

Sah²,

Pond³

et al. 2004

J. Neurosci.

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“…Three days after tGCI, however, more than 80% of the CA1 neurons were degenerated in the Wt rats, as described previously (Chan et al, 1998;Sugawara et al, 1999).…”

Section: Delayed Hippocampal Ca1 Neuronal Death Occurred 72 H After Tsupporting

confidence: 58%

Activation of the Akt/GSK3β Signaling Pathway Mediates Survival of Vulnerable Hippocampal Neurons after Transient Global Cerebral Ischemia in Rats

Endo

Nito

Kamada

et al. 2006

J Cereb Blood Flow Metab

171

113

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Recent studies have revealed that the phosphatidylinositol 3-kinase (PI3-K) pathway is involved in apoptotic cell death after experimental cerebral ischemia. The serine-threonine kinase, Akt, functions in the PI3-K pathway and prevents apoptosis by phosphorylation at Ser473 after a variety of cell death stimuli. After phosphorylation, activated Akt inactivates other apoptogenic factors, including glycogen synthase kinase-3b (GSK3b), thereby inhibiting cell death. However, the role of Akt/GSK3b signaling in the delayed death of hippocampal neurons in the CA1 subregion after transient global cerebral ischemia (tGCI) has not been clarified. Transient global cerebral ischemia for 5 mins was induced by bilateral common carotid artery occlusion combined with hypotension. Western blot analysis showed a significant increase in phospho-Akt (Ser473) and phospho-GSK3b (Ser9) in the hippocampal CA1 subregion after tGCI. Immunohistochemistry showed that expression of phospho-Akt (Ser473) and phospho-GSK3b (Ser9) was markedly increased in the vulnerable CA1 subregion, but not in the ischemic-tolerant CA3 subregion. Double staining with phospho-GSK3b (Ser9) and terminal deoxynucleotidyl transferase-mediated uridine 5 0 -triphosphate-biotin nick end labeling showed different cellular distributions in the CA1 subregion 3 days after tGCI. Phosphorylation of Akt and GSK3b was prevented by LY294002, a PI3-K inhibitor, which facilitated subsequent DNA fragmentation 3 days after tGCI. Moreover, transgenic rats that overexpress copper/zinc-superoxide dismutase, which is known to be neuroprotective against delayed hippocampal CA1 injury after tGCI, had enhanced and persistent phosphorylation of both Akt and GSK3b after tGCI. These findings suggest that activation of the Akt/GSK3b signaling pathway may mediate survival of vulnerable hippocampal CA1 neurons after tGCI.

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“…One report indicated that it was released as early as 2 h after global ischemia (Sugawara et al, 1999) while another study showed no cytochrome c release until 36 h . A recent study showed no definitive evidence for cytochrome c release or caspase activity after permanent focal ischemia (Gill et al, 2002), and another report revealed no caspase activity despite cytochrome c release after transient focal ischemia (Gill et al, 2002;Yenari et al, 2002).…”

Section: Biphasic Release Of Cytochrome C and Caspase Activity After mentioning

confidence: 99%

Biphasic Cytochrome c Release After Transient Global Ischemia and its Inhibition by Hypothermia

Zhao

Yenari

Cheng

et al. 2005

J Cereb Blood Flow Metab

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Hypothermia is effective in preventing ischemic damage. A caspase-dependent apoptotic pathway is involved in ischemic damage, but how hypothermia inhibits this pathway after global cerebral ischemia has not been well explored. It was determined whether hypothermia protects the brain by altering cytochrome c release and caspase activity. Cerebral ischemia was produced by two-vessel occlusion plus hypotension for 10 mins. Body temperature in hypothermic animals was reduced to 331C before ischemia onset and maintained for 3 h after reperfusion. Western blots of subcellular fractions revealed biphasic cytosolic cytochrome c release, with an initial peak at about 5 h after ischemia, which decreased at 12 to 24 h, and a second, larger peak at 48 h. Caspase-3 and -9 activity increased at 12 and 24 h. A caspase inhibitor, Z-DEVD-FMK, administered 5 and 24 h after ischemia onset, protected hippocampal CA1 neurons from injury and blocked the second cytochrome c peak, suggesting that caspases mediate this second phase. Hypothermia (331C), which prevented CA1 injury, did not inhibit cytochrome c release at 5 h, but reduced cytochrome c release at 48 h. Caspase-3 and -9 activity was markedly attenuated by hypothermia at 12 and 24 h. Thus, biphasic cytochrome c release occurs after transient global ischemia and mild hypothermia protects against ischemic damage by blocking the second phase of cytochrome c release, possibly by blocking caspase activity.

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t Mitochondrial Release of CytochromecCorresponds to the Selective Vulnerability of Hippocampal CA1 Neurons in Rats after Transient Global Cerebral Ischemia

Cited by 210 publications

References 28 publications

Changes in Intracellular Chloride after Oxygen–Glucose Deprivation of the Adult Hippocampal Slice: Effect of Diazepam

Changes in Intracellular Chloride after Oxygen–Glucose Deprivation of the Adult Hippocampal Slice: Effect of Diazepam

Activation of the Akt/GSK3β Signaling Pathway Mediates Survival of Vulnerable Hippocampal Neurons after Transient Global Cerebral Ischemia in Rats

Biphasic Cytochrome c Release After Transient Global Ischemia and its Inhibition by Hypothermia

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