Role of Nrf2 in protection against intracerebral hemorrhage injury in mice.

Nrf2 is a key transcriptional factor for antioxidant response element (ARE)-regulated genes. While its beneficial role has been described for stroke, its contribution to intracerebral hemorrhage (ICH)-induced early brain injury remains to be determined. Using wild-type (WT) and Nrf2 knockout (Nrf2(-/-)) mice, the role of Nrf2 in ICH induced by intracerebral injection of collagenase was investigated.

Effects of EP1 receptor on cerebral blood flow in the middle cerebral artery occlusion model of stroke in mice.

The lipid mediator prostaglandin E2 (PGE2) exhibits diverse biologic activity in a variety of tissues. Four PGE2 receptor subtypes (EP1-4) are involved in various physiologic and pathophysiologic conditions, but differ in tissue distribution, ligand-binding affinity, and coupling to intracellular signaling pathways. To characterize the role of the EP1 receptor, physiologic parameters (mean arterial blood pressure, pH, blood gases PaO2 and PaCO2, and body temperature), cerebral blood flow (CBF), and neuronal cell death were studied in a middle cerebral artery occlusion model of ischemic stroke in wild-type (WT) and EP1 knockout (EP1-/-) mice.

PGD(2) DP1 receptor protects brain from ischemia-reperfusion injury.

Prostaglandin D(2) is the most abundant prostaglandin in the brain. It has long been described as a modulator of the neuroinflammatory process, but little is known regarding the role of its Galpha(s)-coupled receptor, DP1. Therefore, in this study, the effect of the DP1 receptor on the outcome of cerebral ischemia in wildtype (WT) and DP1 knockout (DP1(-/-)) C57Bl/6 mice was investigated.

Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage.

Because heme oxygenase (HO) is the rate limiting enzyme in the degradation of the pro-oxidant hemin/heme from blood, here we investigated the contribution of the inducible HO-1 to early brain injury produced by intracerebral haemorrhage (ICH). We found that after induction of ICH, HO-1 proteins were highly detectable in the peri-ICH region predominantly in microglia/macrophages and endothelial cells. Remarkably, the injury volume was significantly smaller in HO-1 knockout (HO-1-/-) mice than in wild-type controls 24 and 72 h after ICH.

Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury.

The transcriptional factor Nrf2 has a unique role in various physiological stress conditions, but its contribution to ischemia/reperfusion injury has not been fully explored. Therefore, wildtype (WT) and Nrf2 knockout (Nrf2(-/-)) mice were subjected to 90-min occlusion of the middle cerebral artery (MCA) followed by 24-h reperfusion to elucidate Nrf2 contribution in protecting against ischemia/reperfusion injury. Infarct volume, represented as percent of hemispheric volume, was significantly (P<0.

Stimulation of prostaglandin E2-EP3 receptors exacerbates stroke and excitotoxic injury.

The effect of PGE(2) EP3 receptors on injury size was investigated following cerebral ischemia and induced excitotoxicity in mice. Treatment with the selective EP3 agonist ONO-AE-248 significantly and dose-dependently increased infarct size in the middle cerebral artery occlusion model. In a separate experiment, pretreatment with ONO-AE-248 exacerbated the lesion caused by N-methyl-d-aspartic acid-induced acute excitotoxicity.

Stimulation of prostaglandin EP2 receptors prevents NMDA-induced excitotoxicity.

Prostaglandin E(2) (PGE(2)) plays an important role in inflammation and neurologic disorders. The neuromodulatory effects of PGE(2) are mediated through regulation of four G-protein-coupled receptors known as EP1, EP2, EP3, and EP4. The goal of the current study was to determine whether EP2 receptor activation protects neurons from acute NMDA-mediated excitotoxicity.

Inflammation after intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a devastating clinical event without effective therapies. Increasing evidence suggests that inflammatory mechanisms are involved in the progression of ICH-induced brain injury. Inflammation is mediated by cellular components, such as leukocytes and microglia, and molecular components, including prostaglandins, chemokines, cytokines, extracellular proteases, and reactive oxygen species.

Plasma homocysteine and cysteine levels in retinal vein occlusion.

Purpose: To determine plasma homocysteine and cysteine levels in patients with retinal vein occlusion (RVO) and in healthy subjects and to ascertain whether there are statistically significant differences between patients and control subjects.

Methods: In this case-control study, the study group consisted of 75 consecutive patients with RVO: 33 had central retinal vein occlusion (CRVO), and 42 had branch retinal vein occlusion (BRVO). Seventy-two apparently healthy age- and sex-matched subjects served as control subjects.

GPCR antagonists as an alternative to COX-2 inhibitors: a case for the PGE2 EP1 receptor.

A recent article supports the concept that prostaglandin (PG)E(2) EP(1)-receptor antagonists reduce stroke severity and cell damage; could these agents become a substitute for cyclooxygenase (COX)-2 inhibitors? The total activity of COXs--rate-limiting enzymes of PGE(2) synthesis--increases following acute neurological insult. Drugs that offer the beneficial anti-inflammatory and neuroprotective effects of PGs but that limit the negative effects of COX-2 inhibition could provide the next generation of treatment for acute neuronal damage.

Heme oxygenase-1 protects brain from acute excitotoxicity.

Heme oxygenase is a rate-limiting enzyme that degrades heme, a pro-oxidant, into carbon monoxide, iron, and bilirubin. Heme oxygenase has two active isoforms: heme oxygenase-1 and heme oxygenase-2. Heme oxygenase-1 can be induced by various insults.

Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage.

Recent studies suggest a neuroprotective function for heme oxygenase 2 (HO2) in acute brain injury and ischemia. HO2, the main enzyme to degrade the pro-oxidant heme, was tested for its neuroprotective ability in postnatal neuronal cell cultures and in a model of collagenase-induced intracerebral hemorrhage. Genetic deletion of HO2 rendered cultured neurons 32% (P < 0.

Gesture standardization increases the reproducibility of 3D kinematic measurements of the knee joint.

Background: The literature on the 3D kinematics of the knee suggests that the gesture accomplished during kinematic assessment might play a significant role in the values measured. The purpose of this study is to demonstrate that a standardized gesture leads to an increased reproducibility in 3D kinematic measurements of the knee.

Methods: Seventeen healthy male subjects performed series of knee-bends in standardized and unconstrained conditions while their left knee's 3D kinematics were recorded using an optical motion-recording system.

1-hydroxyPGE reduces infarction volume in mouse transient cerebral ischemia.

Differential neurological outcomes due to prostaglandin E2 activating G-protein-coupled prostaglandin E (EP) receptors have been observed. Here, we investigated the action of the EP4/EP3 agonist 1-hydroxyPGE1 (1-OHPGE1) in modulating transient ischemic brain damage. C57BL/6 mice were pretreated 50 min before transient occlusion of the middle cerebral artery with an intraventricular injection of 1-OHPGE1 (0.

The use of an ultrasound bladder scanning device in women undergoing urogynaecologic surgery.

Objective: To compare the accuracy of using a bladder scanner to measure post-voiding residual urine volume with measurement by intermittent catheterization in a postoperative urogynaecology population.

Methods: Prior to implementation of the study, nurses were trained in the use of a bladder ultrasound scanner. Post-void residual urine volume in postoperative patients was assessed by a nurse with the scanner; a second nurse, blinded to the scanner result, then catheterized the patient's bladder.

Prostaglandin EP4 receptor agonist protects against acute neurotoxicity.

Under various abnormal physiologic conditions, overactivation of glutamate-gated ion channel receptor family members, including NMDA receptors, causes increase in COX-2 expression and generation of prostaglandins. PGE(2) exerts its physiologic actions mainly through its PGE(2) prostanoid (EP) receptors. In the present study, the role of the EP4 receptor against NMDA-induced excitotoxicity was investigated.

Stimulation of PGE receptors EP2 and EP4 protects cultured neurons against oxidative stress and cell death following beta-amyloid exposure.

Alzheimer's disease (AD) is associated with gliosis, neuroinflammation and higher levels of prostaglandins. Conflicting roles for cyclooxygenases and prostaglandins in the etiopathology of AD have been reported. We hypothesized that PGE2 signaling through EP2 and EP4 G-protein-coupled receptors could protect against amyloid beta-peptide (Abeta) neurotoxicity by increasing the cAMP signaling cascade.

Prostaglandin EP1 receptor contributes to excitotoxicity and focal ischemic brain damage.

The clinical side effects associated with the inhibition of cyclooxygenase enzymes under pathologic conditions have recently raised concerns. A better understanding of neuroinflammatory mechanisms and neuronal survival requires knowledge of cyclooxygenase downstream pathways, especially PGE2 and its G-protein-coupled receptors. In this study, we postulate that EP1 receptor is one of the mechanisms that propagate neurotoxicity and could be a therapeutic target in brain injury.

Dependence of acetylcholine and ADP dilation of pial arterioles on heme oxygenase after transfusion of cell-free polymeric hemoglobin.

Polymers of cell-free hemoglobin have been designed for clinical use as oxygen carriers, but limited information is available regarding their effects on vascular regulation. We tested the hypothesis that the contribution of heme oxygenase (HO) to acetylcholine-evoked dilation of pial arterioles is upregulated 2 days after polymeric hemoglobin transfusion. Dilator responses to acetylcholine measured by intravital microscopy in anesthetized cats were blocked by superfusion of the HO inhibitor tin protoporphyrin-IX (SnPPIX) in a group that had undergone exchange transfusion with hemoglobin 2 days earlier but not in surgical sham and albumin-transfused groups.

Characterization of heme oxygenase in adult rodent platelets.

Thromboembolism--and its involvement with tissue infarction and ischemic necrosis--continues to be of major importance in the area of vascular biology that affects all areas of clinical medicine. Activated platelets and their aggregations are key initiators in the formation of the thrombus. Several mechanisms have been described to modulate thrombus formation in the circulation, such as prostacyclins and endothelium-derived relaxing factors (the most studied being nitric oxide).

Stroke outcomes in mice lacking the genes for neuronal heme oxygenase-2 and nitric oxide synthase.

Heme oxygenase-2 (HO-2) has been suggested to be a cytoprotective enzyme in a variety of in vivo experimental models. HO-2, the constitutive isozyme, is enriched in neurons and, under normal conditions, accounts for nearly all of brain HO activity. HO-2 deletion (HO-2-/-) leads to increased neurotoxicity in cultured brain cells and increased damage following transient cerebral ischemia in mice.

Expression of prostaglandin E2 synthases in mouse postnatal cortical neurons.

Eicosanoids and the enzymes associated with their metabolism play an active role in the neuroinflammatory process that is often a hallmark of neurodegenerative disorders. Cerebral cortical neurons constitute a highly affected cell population in neurologic disorders. To obtain a cellular model to analyze prostaglandin action and metabolism in cortical neurons, we developed postnatal neuronal cultures from mouse cortex in a serum-free medium.