Thioredoxin (TRX) is induced by a variety of oxidative stimuli and shows cytoprotective roles against oxidative stress. To clarify the possibility of clinical application, we examined the effects of intravenously administered TRX in a model of transient focal cerebral ischemia in this study. Mature male C57BL/6j mice received either continuous intravenous infusion of recombinant human TRX (rhTR...

Activation of poly(ADP-ribose) polymerase (PARP) and subsequent translocation of apoptosis-inducing factor contribute to caspase-independent neuronal injury from N-methyl-d-aspartate, oxygen-glucose deprivation, and ischemic stroke. Some studies have implicated endonuclease G in the DNA fragmentation associated with caspase-independent cell death. Here, we compared wild-type and endonuclease G ...

We describe a series of experiments in which a subhuman primate model was used to create temporary and permanent cerebral ischemia by three separate mechanisms. In the first group of five baboons, a hemodynamic model was produced by creating unilateral and bilateral carotid stenotic lesions of varying degrees with and without associated reduction in systemic perfusion pressure. Only global isch...

We describe a series of experiments in which a subhuman primate model was used to create temporary and permanent cerebral ischemia by three separate mechanisms. In the first group of five baboons, a hemodynamic model was produced by creating unilateral and bilateral carotid stenotic lesions of varying degrees with and without associated reduction in systemic perfusion pressure. Only global isch...

We investigated dextromethorphan, both a dextrorotatory opioid derivative and a clinically tested N-methyl-D-aspartate (NMDA) receptor antagonist, in a rabbit model of transient focal cerebral ischemia. Fourteen rabbits were randomly assigned to treatment with a 20 mg/kg i.v. loading dose followed by a 10 mg/kg/hr infusion of 0.4% dextromethorphan in normal saline or with an equivalent volume o...

We describe a series of experiments in which a subhuman primate model was used to create temporary and permanent cerebral ischemia by three separate mechanisms. In the first group of five baboons, a hemodynamic model was produced by creating unilateral and bilateral carotid stenotic lesions of varying degrees with and without associated reduction in systemic perfusion pressure. Only global isch...

OBJECTIVE Rho-associated kinase (ROCK) is a key regulator of numerous processes in multiple cell types relevant in stroke pathophysiology. ROCK inhibitors have improved outcome in experimental models of acute ischemic or hemorrhagic stroke. However, the relevant ROCK isoform (ROCK1 or ROCK2) in acute stroke is not known. METHODS We characterized the pharmacodynamic and pharmacokinetic profile...

We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in rats at 7 and 30 days after transient middle cerebral artery occlusion (tMCAO), indicating ischemic diaschisis. Here, we focused on effects of subacute and chronic focal cerebral ischemia on the blood-spinal cord barrier (BSCB). We observed BSCB damage on both sides of the cervical spinal cord in ra...

Despite immunophilins being abundant in the brain,their functional role there remains unclear. Using rat models of transient focal cerebral ischemia,I investigated the effect of ischemic stress on the rotamase activity of immunophilins in the brain and examined the possible role of immunophilins in postischemic neuroprotection. I found that the rotamase activity of the FK506 binding protein cla...

BACKGROUND AND PURPOSE The purpose of this study was to test the hypothesis that nitric oxide is required for preconditioning in an intact animal model of focal ischemia using neuronal and endothelial nitric oxide synthase (nNOS and eNOS) knockout mice. METHODS Cerebral blood flow was measured in wild-type, nNOS knockout, and eNOS knockout mice by hydrogen clearance (absolute) and laser Doppl...