Dual role of nitric oxide in focal cerebral ischemia

Dalkara, Turgay; Yoshida, Tomoo; Irikura, Katsumi; Moskowitz, Michael A.

doi:10.1016/0028-3908(94)90048-5

Cited by 136 publications

(58 citation statements)

References 20 publications

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“…CaN is also an enzyme involved in dephosphorylation of nNOS processes and increase of its activity. The experimental data indicate that NO production by nNOS (also functioning in glial cells) and consequently, free radicals produced from NO exacerbate ischemic brain cells injury (10,11,47).…”

Section: +mentioning

confidence: 97%

“…However, many authors postulated that neuroprotective effects of FK506 and CsA could be functionally separated from their immunosuppressive properties (8,9). One hypothesis concerning cellular mechanisms of FK506 and CsA protective action is that these compounds act as neuroprotectants, presumably through CaN inhibition, which prevent dephosphorylation / activation of nNOS and subsequent NO mediated toxicity (10,11). A link to inhibition of phospholipase A 2 (PLA 2 ) was also suggested since attenuation of free fatty acids liberation was supposed to prevent the assembly of a mitochondrial permeability transition pore (MPTP).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro

Gabryel¹,

Chalimoniuk²,

Stolecka³

et al. 2006

J Pharmacol Sci

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Section: +mentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro

Gabryel¹,

Chalimoniuk²,

Stolecka³

et al. 2006

J Pharmacol Sci

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“…Therefore, endothelial NO appears to act as a neuroprotective signal against hypoxic-ischemia. This has been supported by recent findings that show that the inhibition of eNOS worsens neuronal death after hypoxic-ischemia (Dalkara et al, 1994;Shapira et al, 1994;Stagliano et al, 1997). Finally, the expression of iNOS increased in glial cells and neutrophils several days after reperfusion, which provided a substantial amount of NO in the ischemic area (Iadecola et al, 1995a).…”

Section: Production Of Reactive Oxygen Species In Mitochondriamentioning

confidence: 54%

Cellular and Molecular Pathways of Ischemic Neuronal Death

Won¹,

Kim²,

Gwag³

2002

BMB Reports

201

172

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Three routes have been identified triggering neuronal death under physiological and pathological conditions. Excess activation of ionotropic glutamate receptors cause influx and accumulation of Ca 2+ and Na + that result in rapid swelling and subsequent neuronal death within a few hours. The second route is caused by oxidative stress due to accumulation of reactive oxygen and nitrogen species. Apoptosis or programmed cell death that often occurs during developmental process has been coined as additional route to pathological neuronal death in the mature nervous system. Evidence is being accumulated that excitotoxicity, oxidative stress, and apoptosis propagate through distinctive and mutually exclusive signal transduction pathway and contribute to neuronal loss following hypoxic-ischemic brain injury. Thus, the therapeutic intervention of hypoxic-ischemic neuronal injury should be aimed to prevent excitotoxicity, oxidative stress, and apoptosis in a concerted way.

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“…Some of these beneficial effects may relate to the effects of statins on endothelial and platelet function. Cerebrovascular tone and blood flow are regulated by endothelium-derived NO (157). Mutant mice lacking eNOS (eNOS −/− ) are relatively hypertensive and develop greater proliferative and inflammatory response to vascular injury (158).…”

Section: Statins and Ischemic Strokementioning

confidence: 99%

Pleiotropic Effects of Statins

Liao

Laufs

2005

Annu. Rev. Pharmacol. Toxicol.

1,595

1,198

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Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. Indeed, recent studies indicate that some of the cholesterol-independent or "pleiotropic" effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Furthermore, statins have beneficial extrahepatic effects on the immune system, CNS, and bone. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in mediating the pleiotropic effects of statins.

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Dual role of nitric oxide in focal cerebral ischemia

Cited by 136 publications

References 20 publications

Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro

Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro

Cellular and Molecular Pathways of Ischemic Neuronal Death

Pleiotropic Effects of Statins

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