Ethanol-Induced Suppression of G Protein-Gated Inwardly Rectifying K-Dependent Signaling in the Basal Amygdala.

Background: The basolateral amygdala (BLA) regulates mood and associative learning and has been linked to the development and persistence of alcohol use disorder. The GABAR (gamma-aminobutyric acid B receptor) is a promising therapeutic target for alcohol use disorder, and previous work suggests that exposure to ethanol and other drugs can alter neuronal GABAR-dependent signaling. The effect of ethanol on GABAR-dependent signaling in the BLA is unknown.

Pipeline embolization of MCA aneurysms in the M2-M4 segment: Dual center study and meta-analysis.

Objective: Flow diversion of distal MCA aneurysms in the M2-M4 segments with Pipeline embolization device is promising, but further study is needed. Here, we seek to quantify the safety and efficacy of Pipeline embolization in the M2-M4 region in a dual-center cohort and comprehensive meta-analysis.

Methods: Clinical and angiographic data of eligible patients was obtained from participating centers.

Effect of Intensive Glucose Control on Outcomes of Hyperglycemic Stroke Patients Receiving Mechanical Thrombectomy: Secondary Analysis of the SHINE Trial.

Background: Hyperglycemia is common among patients presenting with acute ischemic stroke (AIS) and is associated with poor clinical outcomes. We studied the effects of intensive blood glucose control among AIS patients presenting with hyperglycemia treated with mechanical thrombectomy (MT).

Methods: We analyzed publicly available data from the Stroke Hyperglycemia Insulin Network Effort trial.

Outcomes of Homeless Ischemic Stroke Patients Receiving Intravenous Thrombolysis in the United States.

Background: Morbidity and mortality among homeless people with cardiovascular diseases and stroke in the United States is high. Adverse outcomes within the homeless population may be the result of seeking care too late to receive time-sensitive interventions. We sought to investigate the impact of homelessness on ischemic stroke patients who received intravenous thrombolysis (IVT).

Pipeline embolization of proximal middle cerebral artery aneurysms: A multicenter cohort study.

Background And Purpose: Flow diversion of aneurysms located in the M1 segment and middle cerebral artery bifurcation with Pipeline embolization device is sometimes performed, but further study is needed to support its regular use in aneurysm treatment. Here, we report measures of safety and efficacy for Pipeline embolization in the proximal middle cerebral artery in a multi-center cohort.

Materials And Methods: Clinical and angiographic data of eligible patients were retrospectively obtained from participating centers and assessed for key clinical and angiographic outcomes.

Pipeline embolization of distal posterior inferior cerebellar artery aneurysms.

Background And Purpose: Flow diversion is commonly used to treat intracranial aneurysms in various regions of the cerebral vasculature, but is only approved for use in the internal carotid arteries. Treatment of distal PICA aneurysms with PED is sometimes performed but has not been well studied. Here, we report our experience with flow diversion of distal PICA aneurysms with PED.

Impact of Acute and Persistent Excitation of Prelimbic Pyramidal Neurons on Motor Activity and Trace Fear Learning.

Drug-induced neuroadaptations in the mPFC have been implicated in addictive behaviors. Repeated cocaine exposure has been shown to increase pyramidal neuron excitability in the prelimbic (PL) region of the mouse mPFC, an adaptation attributable to a suppression of G protein-gated inwardly rectifying K (GIRK) channel activity. After establishing that this neuroadaptation is not seen in adjacent GABA neurons, we used viral GIRK channel ablation and complementary chemogenetic approaches to selectively enhance PL pyramidal neuron excitability in adult mice, to evaluate the impact of this form of plasticity on PL-dependent behaviors.

Quality of life among ischemic stroke patients eligible for endovascular treatment: analysis of the DEFUSE 3 trial.

Background: The endovascular treatment (ET) for acute ischemic stroke is increasing among eligible patients. Assessing patients' perspectives on quality of life (QOL) can supplement the use of formal outcome scales and enable the assessment of outcomes across multiple domains affected by stroke.

Methods: We analyzed publicly available data from the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE 3) trial.

Predictive value of discharge destination for 90-day outcomes among ischemic stroke patients eligible for endovascular treatment: Post-hoc analysis of DEFUSE 3.

Background: The endovascular treatment (ET) for acute ischemic stroke (AIS) is increasing among eligible patients. To help address care quality, administrative data sets are utilized but do not usually include formal outcome scales. We explore the predictive ability of discharge destination from acute hospitalizations for long-term disability among AIS patients eligible for ET within a clinical trial.

Dual antiplatelet therapy does not improve outcomes after aneurysmal subarachnoid hemorrhage compared with aspirin monotherapy.

Background: The pathophysiology of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) may include platelet activation and microthrombi formation. Antiplatelet therapy may reduce the incidence of DCI and improve clinical outcomes after aSAH. This study compared outcomes among aSAH patients receiving aspirin monotherapy versus dual antiplatelet therapy (DAPT).

Weekday Versus Weekend Presentation in the Acute Management of Ischemic Stroke Through Telemedicine.

A "weekend effect" resulting in higher mortality rates for patients with stroke admitted on weekends has been reported. We examine this phenomenon for patients with acute ischemic stroke (AIS) presenting to telestroke (TS) sites to determine its effect on stroke alert process times and outcomes. From October 2015 to June 2017, we reviewed patients with AIS receiving intravenous alteplase within our TS network.

Conivaptan for the Reduction of Cerebral Edema in Intracerebral Hemorrhage: A Safety and Tolerability Study.

Background: Perihematomal edema (PHE) growth in intracranial hemorrhage (ICH) is a biomarker for worse outcomes. Although the management of PHE is potentially beneficial for ICH patients, there is currently no proven clinical therapy that both reduces PHE and improves outcomes in this population.

Objective: To examine the safety and tolerability of conivaptan, a non-peptide vasopressin (AVP) receptor antagonist, for the management of PHE in ICH patients.

Utility of procalcitonin for diagnosis of bacterial infection-related systemic inflammatory response in the acute neurologic injury population.

Objective: Inflammation and bacterial infection are common complicating factors in the treatment of patients with stroke. Inflammatory responses can manifest as systemic inflammatory response syndrome (SIRS), a condition with both infectious and non-infectious etiologies. Accurately identifying patients with infection-related SIRS is important for determining the correct treatment plan.

Identification and characterization of heptapeptide modulators of the glycine receptor.

The glycine receptor is a member of the Cys-loop receptor superfamily of ligand-gated ion channels and is implicated as a possible therapeutic target for the treatment of diseases such as alcoholism and inflammatory pain. In humans, four glycine receptor subtypes (α1, α2, α3, and β) co-assemble to form pentameric channel proteins as either α homomers or αβ heteromers. To date, few agents have been identified that can selectively modulate the glycine receptor, especially those possessing subtype specificity.

G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 Knock-Out Mice Show Enhanced Ethanol Reward.

Background: G protein-gated inwardly rectifying potassium (GIRK) channels contribute to the effects of a number of drugs of abuse, including ethanol. However, the roles of individual subunits in the rewarding effects of ethanol are poorly understood.

Methods: We compare conditioned place preference (CPP) in GIRK3 subunit knock-out (GIRK3(-/-)), heterozygote (GIRK3(+/-)), and wild-type (WT) mice.

GIRK Channels: A Potential Link Between Learning and Addiction.

The ability of drug-associated cues to reinitiate drug craving and seeking, even after long periods of abstinence, has led to the hypothesis that addiction represents a form of pathological learning, in which drugs of abuse hijack normal learning and memory processes to support long-term addictive behaviors. In this chapter, we review evidence suggesting that G protein-gated inwardly rectifying potassium (GIRK/Kir3) channels are one mechanism through which numerous drugs of abuse can modulate learning and memory processes. We will examine the role of GIRK channels in two forms of experience-dependent long-term changes in neuronal function: homeostatic plasticity and synaptic plasticity.

Acute ethanol withdrawal impairs contextual learning and enhances cued learning.

Background: Alcohol affects many of the brain regions and neural processes that support learning and memory, and these effects are thought to underlie, at least in part, the development of addiction. Although much work has been done regarding the effects of alcohol intoxication on learning and memory, little is known about the effects of acute withdrawal from a single alcohol exposure.

Methods: We assess the effects of acute ethanol withdrawal (6 hours postinjection with 4 g/kg ethanol) on 2 forms of fear conditioning (delay and trace fear conditioning) in C57BL/6J and DBA/2J mice.

Delay and trace fear conditioning in C57BL/6 and DBA/2 mice: issues of measurement and performance.

Strain comparison studies have been critical to the identification of novel genetic and molecular mechanisms in learning and memory. However, even within a single learning paradigm, the behavioral data for the same strain can vary greatly, making it difficult to form meaningful conclusions at both the behavioral and cellular level. In fear conditioning, there is a high level of variability across reports, especially regarding responses to the conditioned stimulus (CS).

Behavioral disinhibition in mice bred for high drinking in the dark (HDID) and HS controls increases following ethanol.

Background: Alcohol consumption and behavioral inhibition share some common underlying genetic mechanisms. The current study examined whether lines of mice selected for high blood ethanol concentrations, attained by heavy drinking in the dark period (DID) of the light-dark cycle that models binge drinking, also exhibit higher levels of drug-naïve inhibition. It also examined whether the administration of ethanol would result in higher levels of disinhibition in these selected lines compared to the founder stock (HS).

Substance abuse, memory, and post-traumatic stress disorder.

A large body of literature demonstrates the effects of abused substances on memory. These effects differ depending on the drug, the pattern of delivery (acute or chronic), and the drug state at the time of learning or assessment. Substance use disorders involving these drugs are often comorbid with anxiety disorders, such as post-traumatic stress disorder (PTSD).

Trifluoroacetate is an allosteric modulator with selective actions at the glycine receptor.

Trifluoroacetic acid is a metabolite of the inhaled anesthetics halothane, desflurane and isoflurane as well as a major contaminant in HPLC-purified peptides. Ligand-gated ion channels, including cys-loop receptors such as the glycine receptor, have been the targets of peptide-based drug design and are considered to be likely candidates for mediating the effects of anesthetics in vivo, but the possible secondary contributions of contaminants and metabolites to these effects have not been studied. We used two-electrode voltage-clamp electrophysiology to test glycine, GABA(A) and 5-HT3 receptors expressed in Xenopus oocytes for their sensitivities to sodium trifluoroacetate.

Identification of novel specific allosteric modulators of the glycine receptor using phage display.

The glycine receptor (GlyR) is a member of the Cys-loop superfamily of ligand-gated ion channels and the major mediator of inhibitory neurotransmission in the spinal cord and brainstem. Many allosteric modulators affect the functioning of members of this superfamily, with some such as benzodiazepines showing great specificity and others such as zinc, alcohols, and volatile anesthetics acting on multiple members. To date, no potent and efficacious allosteric modulator acting specifically at the GlyR has been identified, hindering both experimental characterization of the receptor and development of GlyR-related therapeutics.