Abstract | BACKGROUND AND PURPOSE: The identification of a neuroprotective drug for stroke remains elusive. Given that mitochondria play a key role both in maintaining cellular energetic homeostasis and in triggering the activation of cell death pathways, we evaluated the efficacy of newly identified inhibitors of cytochrome c release in hypoxia/ ischemia induced cell death. We demonstrate that methazolamide and melatonin are protective in cellular and in vivo models of neuronal hypoxia. METHODS: RESULTS:
Methazolamide and melatonin inhibit oxygen/ glucose deprivation-induced cell death, loss of mitochondrial membrane potential, release of mitochondrial factors, pro-IL-1beta processing, and activation of caspase-1 and -3 in primary cerebrocortical neurons. Furthermore, they decrease infarct size and improve neurological scores after middle cerebral artery occlusion in mice. CONCLUSIONS:
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Authors | Xin Wang, Bryan E Figueroa, Irina G Stavrovskaya, Yi Zhang, Ana C Sirianni, Shan Zhu, Arthur L Day, Bruce S Kristal, Robert M Friedlander |
Journal | Stroke
(Stroke)
Vol. 40
Issue 5
Pg. 1877-85
(May 2009)
ISSN: 1524-4628 [Electronic] United States |
PMID | 19299628
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antioxidants
- Carbonic Anhydrase Inhibitors
- Interleukin-1beta
- Neuroprotective Agents
- Cytochromes c
- L-Lactate Dehydrogenase
- Caspase 3
- Caspase 1
- Melatonin
- Methazolamide
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Topics |
- Animals
- Antioxidants
(pharmacology)
- Blotting, Western
- Brain Ischemia
(pathology, prevention & control)
- Carbonic Anhydrase Inhibitors
(pharmacology)
- Caspase 1
(metabolism)
- Caspase 3
(metabolism)
- Cell Death
(drug effects)
- Cytochromes c
(metabolism)
- Enzyme Activation
(drug effects)
- In Situ Nick-End Labeling
- Interleukin-1beta
(metabolism)
- L-Lactate Dehydrogenase
(metabolism)
- Melatonin
(pharmacology)
- Membrane Potentials
(drug effects)
- Methazolamide
(pharmacology)
- Mice
- Mice, Inbred C57BL
- Mitochondria
(drug effects, enzymology)
- Mitochondrial Membranes
(drug effects)
- Neurodegenerative Diseases
(pathology)
- Neurons
(pathology)
- Neuroprotective Agents
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