Publications by authors named "James J Ley"

Stilbazulenyl nitrone (STAZN) is a potent antioxidant that, in a rat model of transient focal cerebral ischemia, confers significant enduring functional and morphological neuroprotection. This study investigated the influence of dose and time of administration on the neuroprotective effects of STAZN in the intraluminal suture model of middle cerebral artery occlusion (MCAo). Dose response: At 2 and 4 h after the onset of MCAo, animals received intravenously either STAZN (low dose=0.

View Article and Find Full Text PDF

Background: Protecting the myocardium from ischemia-reperfusion injury has significant potential to reduce the complications of myocardial infarction and interventional revascularization procedures. Reperfusion damage is thought to result, in part, from oxidative stress. Here we use a novel method of percutaneous coronary occlusion to show that the potent antioxidant and neuroprotective free-radical scavenger, stilbazulenyl nitrone (STAZN), confers marked cardioprotection when given immediately prior to reperfusion.

View Article and Find Full Text PDF

Stilbazulenyl nitrone (STAZN) is a potent lipophilic second-generation azulenyl nitrone antioxidant, which is highly neuroprotective in rodent models of cerebral ischemia and trauma. This study was conducted to establish whether the neuroprotection induced by STAZN persists with chronic survival and to characterize STAZN's pharmacokinetics. Physiologically regulated rats received a 2-h middle cerebral artery occlusion by intraluminal suture and were treated with either STAZN [four 0.

View Article and Find Full Text PDF

Oxidative stress plays an important role in neuronal death in neurodegenerative disorders such as Parkinson's disease (PD) and Huntington's disease (HD). Animal models of PD or HD, produced by administration of the mitochondrial toxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 3-nitropropionic acid (3NP), respectively, show increased free radical generation. Free radicals generated in biological systems can react with spin-trapping compounds, such as nitrones, to form stable adducts.

View Article and Find Full Text PDF

The rate constants, k(inh), for reaction of stilbazulenyl-bis-nitrone (STAZN, 1) with peroxyl radicals and the number of radicals trapped, n, are compared with those of phenolic antioxidants 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMHC, 4a), 2,5,7,8-tetramethyl-6-hydroxychroman-2-carboxylic acid (Trolox, 4b), and 2,6-di-tert-butyl-4-methoxyphenol (DBHA, 5). The behavior of STAZN depended markedly on the media and type of initiator used, water-soluble or lipid-soluble. In styrene/chlorobenzene and initiation by azo-bis(isobutyronitrile) (AIBN), k(inh) (STAZN) = 0.

View Article and Find Full Text PDF

Azulenyl nitrones are novel chain-breaking antioxidants with low oxidation potentials and high lipophilicity-properties favoring their efficacy as neuroprotectants. We tested the second-generation azulenyl nitrone, stilbazunenlyl nitrone (STAZN), in focal ischemic stroke. Physiologically monitored rats received 2 hours of middle cerebral artery occlusion by intraluminal suture, resulting in substantial cortical and striatal infarcation.

View Article and Find Full Text PDF

Object: Stilbazulenyl nitrone (STAZN) is a second-generation azulenyl nitrone that has markedly enhanced antioxidant properties compared with those of conventional alpha-phenyl nitrones. In this study, the authors assessed the potential efficacy of STAZN in a rodent model of fluid-percussion brain injury, which results in a consistent cortical contusion.

Methods: After anesthesia had been induced in normothermic Sprague-Dawley rats (brain temperature 36-36.

View Article and Find Full Text PDF

Stilbazulenyl nitrone (STAZN), 8, a nitronyl-substituted hydrocarbon, is a novel second-generation azulenyl nitrone with significantly enhanced potency as a chain-breaking antioxidant vs conventional alpha-phenyl nitrones previously investigated as antioxidant therapeutics. A convenient (1)H NMR-based assay for assessing the potency of chain-breaking antioxidants has shown that STAZN is ca. 300 times more potent in inhibiting the free radical-mediated aerobic peroxidation of cumene than is PBN and the experimental stroke drug NXY-059.

View Article and Find Full Text PDF