CPP impairs contextual learning at concentrations below those that block pyramidal neuron NMDARs and LTP in the CA1 region of the hippocampus.

Drugs that block N-methyl-d-aspartate receptors (NMDARs) suppress hippocampus-dependent memory formation; they also block long-term potentiation (LTP), a cellular model of learning and memory. However, the fractional block that is required to achieve these effects is unknown. Here, we measured the dose-dependent suppression of contextual memory in vivo by systemic administration of the competitive antagonist (R,S)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP); in parallel, we measured the concentration-dependent block by CPP of NMDAR-mediated synapses and LTP of excitatory synapses in hippocampal brain slices in vitro.

Impact of renal function in high bleeding risk patients undergoing percutaneous coronary intervention: a patient-level stratified analysis from four post-approval studies.

Data on ischemic and bleeding outcomes after percutaneous coronary intervention (PCI) in high bleeding risk (HBR) patients with chronic kidney disease (CKD) are scarce. We aimed to evaluate the association between CKD and ischemic and bleeding outcomes in HBR patients who underwent PCI. Among 10,502 patients in the four post-approval registries evaluating patients undergoing PCI, 2,300 patients presented with at least one major or two minor ARC-HBR criteria.

Long-Term Safety and Efficacy of Durable Polymer Cobalt-Chromium Everolimus-Eluting Stents in Patients at High Bleeding Risk: A Patient-Level Stratified Analysis From Four Postapproval Studies.

Background: Long-term outcomes in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention with a drug-eluting stent are unclear. Therefore, we aimed to evaluate long-term adverse events in HBR patients undergoing percutaneous coronary intervention with cobalt-chromium everolimus-eluting stent implantation.

Methods: We analyzed stratified data from 4 all-comers postapproval registries.

Induction and Expression of Fear Sensitization Caused by Acute Traumatic Stress.

Fear promotes adaptive responses to threats. However, when the level of fear is not proportional to the level of threat, maladaptive fear-related behaviors characteristic of anxiety disorders result. Post-traumatic stress disorder develops in response to a traumatic event, and patients often show sensitized reactions to mild stressors associated with the trauma.

Delayed environmental enrichment reverses sevoflurane-induced memory impairment in rats.

Background: Anesthesia given to immature rodents causes cognitive decline, raising the possibility that the same might be true for millions of children undergoing surgical procedures under general anesthesia each year. We tested the hypothesis that anesthesia-induced cognitive decline in rats is treatable. We also tested if anesthesia-induced cognitive decline is aggravated by tissue injury.

Gamma-aminobutyric acid type A receptor β3 subunit forebrain-specific knockout mice are resistant to the amnestic effect of isoflurane.

Background: β3 containing γ-aminobutyric acid type A receptors (GABA(A)-Rs) mediate behavioral end points of IV anesthetics such as immobility and hypnosis. A knockout mouse with targeted forebrain deletion of the β3 subunit of the GABA(A)-R shows reduced sensitivity to the hypnotic effect of etomidate, as measured by the loss of righting reflex. The end points of amnesia and immobility produced by an inhaled anesthetic have yet to be evaluated in this conditional knockout.

Slowing of the hippocampal θ rhythm correlates with anesthetic-induced amnesia.

Background: Temporary, antegrade amnesia is one of the core desirable endpoints of general anesthesia. Multiple lines of evidence support a role for the hippocampal θ rhythm, a synchronized rhythmic oscillation of field potentials at 4-12 Hz, in memory formation. Previous studies have revealed a disruption of the θ rhythm at surgical levels of anesthesia.

Amygdala transcriptome and cellular mechanisms underlying stress-enhanced fear learning in a rat model of posttraumatic stress disorder.

Severe stress or trauma can cause permanent changes in brain circuitry, leading to dysregulation of fear responses and the development of posttraumatic stress disorder (PTSD). To date, little is known about the molecular mechanisms underlying stress-induced long-term plasticity in fear circuits. We addressed this question by using global gene expression profiling in an animal model of PTSD, stress-enhanced fear learning (SEFL).

Gamma-aminobutyric acid type A receptor alpha 4 subunit knockout mice are resistant to the amnestic effect of isoflurane.

Background: General anesthesia produces multiple end points including immobility, hypnosis, sedation, and amnesia. Tonic inhibition via gamma-aminobutyric acid type A receptors (GABA(A)-Rs) may play a role in mediating behavioral end points that are suppressed by low concentrations of anesthetics (e.g.

Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats.

Background: Anesthetic agents cause cell death in the developing rodent brain and long-term, mostly hippocampal-dependent, neurocognitive dysfunction. However, a causal link between these findings has not been shown. Postnatal hippocampal neurogenesis affects hippocampal function into adulthood; therefore, the authors tested the hypothesis that isoflurane affects long-term neurocognitive function via an effect on dentate gyrus neurogenesis.

Effect of hypercarbia and isoflurane on brain cell death and neurocognitive dysfunction in 7-day-old rats.

Background: Millions of neonates undergo anesthesia each year. Certain anesthetic agents cause brain cell death and long-term neurocognitive dysfunction in postnatal day (P)7 rats. Despite its intuitive appeal, a causal link between cell death and neurocognitive decline after anesthesia has not been established.

Isoflurane suppresses stress-enhanced fear learning in a rodent model of post-traumatic stress disorder.

Background: A minority of patients who experience awareness and/or pain during surgery subsequently develop post-traumatic stress disorder. In a rodent model of post-traumatic stress disorder, stress-enhanced fear learning (SEFL), rats are preexposed to a stressor of 15 foot shocks. Subsequent exposure to a single foot shock produces an enhanced fear response.

Exposure to a stressor produces a long lasting enhancement of fear learning in rats.

In contextual fear conditioning, footshock is given in a context, and re-exposure to this context elicits the conditional defensive response of freezing, a reliable behavioral index of conditional fear. Normally, the amount of contextual freezing is directly proportional to the number of shocks an animal receives in the context. However, pre-exposure to a stressor can produce an enhancement in conditional freezing.

Stress-induced enhancement of fear learning: an animal model of posttraumatic stress disorder.

Fear is an adaptive response that initiates defensive behavior to protect animals and humans from danger. However, anxiety disorders, such as Posttraumatic Stress Disorder (PTSD), can occur when fear is inappropriately regulated. Fear conditioning can be used to study aspects of PTSD, and we have developed a model in which pre-exposure to a stressor of repeated footshock enhances conditional fear responding to a single context-shock pairing.

Indomethacin attenuates hyperthermia produced by anterior coronal lateral hypothalamic knife cuts.

Electrolytic lesions of the lateral hypothalamus (LH) and coronal knife cuts of fibers anterior to the LH produce an elevation in core body temperature, or hyperthermia. Prostaglandin has been shown to mediate hyperthermia produced by electrolytic LH lesions. The present study characterizes the time course and the role of prostaglandin in mediating knife-cut-induced hyperthermia.