Cytosolic phospholipase A2 alpha amplifies early cyclooxygenase-2 expression, oxidative stress and MAP kinase phosphorylation after cerebral ischemia in mice.

Background: The enzyme cytosolic phospholipase A2 alpha (cPLA2alpha) has been implicated in the progression of cerebral injury following ischemia and reperfusion. Previous studies in rodents suggest that cPLA2alpha enhances delayed injury extension and disruption of the blood brain barrier many hours after reperfusion. In this study we investigated the role of cPLA2alpha in early ischemic cerebral injury.

Early treatment of transient focal cerebral ischemia with bovine PEGylated carboxy hemoglobin transfusion.

The effect of transfusion of PEGylated hemoglobin (PEG-Hb) was evaluated in anesthetized rats subjected to 2 hours of focal cerebral ischemia and 1 day of reperfusion. PEG-Hb was stored in the carboxy state (PEG-COHb) to reduce autooxidation and increase the shelf life. Transfusion of 10 ml/kg of PEG-COHb at 20 minutes of ischemia did not alter arterial blood pressure or increase red cell flux in the ischemic core.

Contributions of poly(ADP-ribose) polymerase-1 and -2 to nuclear translocation of apoptosis-inducing factor and injury from focal cerebral ischemia.

Excessive oxidative damage to DNA leads to activation of poly(ADP-ribose) polymerase-1 (PARP-1), accumulation of PAR polymers, translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus, and cell death. In this study, we compared the effect of gene deletion of PARP-1 and PARP-2, enzymes activated by DNA oxidative damage, in male mice subjected to 2 h of focal cerebral ischemia. Infarct volume at 3 days of reperfusion was markedly decreased to a similar extent in PARP-1- and PARP-2-null mice.

Effect of 20-HETE inhibition on infarct volume and cerebral blood flow after transient middle cerebral artery occlusion.

This study examined the effects of an inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis, N-(3-chloro-4-morpholin-4-yl)phenyl-N'-hydroxyimido formamide (TS-011), on infarct volume, volume at risk, cerebral blood flow (CBF), and levels of cytochrome P450 (CYP450) eicosanoids in the brain after transient occlusion of the middle cerebral artery (t-MCAO) in rats. TS-011 (0.1 mg/kg, iv) reduced cortical infarct volume by approximately 70% and total infarct volume by 55%.

Delayed tolerance with repetitive transient focal ischemic preconditioning in the mouse.

Background And Purpose: Transient ischemic attacks have long been regarded as a risk factor for the incidence of stroke but may reduce the severity of stroke by inducing ischemic tolerance. The present objective was to develop an ischemic preconditioning (IPC) model of delayed tolerance in the mouse based on repetitive, transient middle cerebral artery occlusion (MCAO).

Methods: Mice anesthetized with halothane or isoflurane underwent IPC, which consisted of repetitive MCAO at 45-minute intervals by the intraluminal filament technique.

Poly(ADP-ribose) (PAR) polymer is a death signal.

Excessive activation of the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) plays a prominent role in various of models of cellular injury. Here, we identify poly(ADP-ribose) (PAR) polymer, a product of PARP-1 activity, as a previously uncharacterized cell death signal. PAR polymer is directly toxic to neurons, and degradation of PAR polymer by poly(ADP-ribose) glycohydrolase (PARG) or phosphodiesterase 1 prevents PAR polymer-induced cell death.

Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection.

Estrogen reduces brain injury after experimental cerebral ischemia in part through a genomic mechanism of action. Using DNA microarrays, we analyzed the genomic response of the brain to estradiol, and we identified a transcript, cocaine- and amphetamine-regulated transcript (CART), that is highly induced in the cerebral cortex by estradiol under ischemic conditions. Using in vitro and in vivo models of neural injury, we confirmed and characterized CART mRNA and protein up-regulation by estradiol in surviving neurons, and we demonstrated that i.

Quantitative description of proton exchange processes between water and endogenous and exogenous agents for WEX, CEST, and APT experiments.

The proton exchange processes between water and solutes containing exchangeable protons have recently become of interest for monitoring pH effects, detecting cellular mobile proteins and peptides, and enhancing the detection sensitivity of various low-concentration endogenous and exogenous species. In this work, the analytic expressions for water exchange (WEX) filter spectroscopy, chemical exchange-dependent saturation transfer (CEST), and amide proton transfer (APT) experiments are derived by the use of Bloch equations with exchange terms. The effects of the initial states for the system, the difference between a steady state and a saturation state, and the relative contributions of the forward and backward exchange processes are discussed.

Pain evaluation and response to buprenorphine in rats subjected to sham middle cerebral artery occlusion.

Appropriate and efficacious use of analgesics in rodents must be balanced judiciously between animal needs and research objectives. A concern in many studies is that analgesia will confound experimental outcome or interpretation. Accordingly, determining whether rats subjected to surgical protocols show evidence of pain is important if we are to provide rational postoperative analgesia without compromising experimental objectives.

Neuroprotection and P450 2C11 upregulation after experimental transient ischemic attack.

Background And Purpose: Transient ischemic attack (TIA) is a risk factor for stroke. However, TIA may also serve as a preconditioning stimulus, reducing damage from subsequent stroke. We tested the hypothesis that experimental TIA induces expression of P450 2C11, an arachidonic acid epoxygenase that produces vasodilator epoxyeicosatrienoic acids, leading to increased tissue perfusion and reduced stroke damage.