Abstract:
OBJECTIVES:Cognitive deficits after traumatic brain injury are a leading cause of disability worldwide, yet no effective pharmacologic treatments exist to improve cognition. Traumatic brain injury increases proinflammatory cytokines, which trigger excess function of α5 subunit-containing γ-aminobutyric acid type A receptors. In several models of brain injury, drugs that inhibit α5 subunit-containing γ-aminobutyric acid type A receptor function improve cognitive performance. Thus, we postulated that inhibiting α5 subunit-containing γ-aminobutyric acid type A receptors would improve cognitive performance after traumatic brain injury. In addition, because traumatic brain injury reduces long-term potentiation in the hippocampus, a cellular correlate of memory, we studied whether inhibition of α5 subunit-containing γ-aminobutyric acid type A receptors attenuated deficits in long-term potentiation after traumatic brain injury. DESIGN:Experimental animal study. SETTING:Research laboratory. SUBJECTS:Adult male mice and hippocampal brain slices. INTERVENTIONS:Anesthetized mice were subjected to traumatic brain injury with a closed-head, free-weight drop method. One week later, the mice were treated with L-655,708 (0.5 mg/kg), an inhibitor that is selective for α5 subunit-containing γ-aminobutyric acid type A receptors, 30 minutes before undergoing behavioral testing. Problem-solving abilities were assessed using the puzzle box assay, and memory performance was studied with novel object recognition and object place recognition assays. In addition, hippocampal slices were prepared 1 week after traumatic brain injury, and long-term potentiation was studied using field recordings in the cornu Ammonis 1 region of slices that were perfused with L-655,708 (100 nM). MEASUREMENTS AND MAIN RESULTS:Traumatic brain injury increased the time required to solve difficult but not simple tasks in the puzzle box assay and impaired memory in the novel object recognition and object place recognition assays. L-655,708 improved both problem solving and memory in the traumatic brain injury mice. Traumatic brain injury reduced long-term potentiation in the hippocampal slices, and L-655,708 attenuated this reduction. CONCLUSIONS:Pharmacologic inhibition of α5 subunit-containing γ-aminobutyric acid type A receptors attenuated cognitive deficits after traumatic brain injury and enhanced synaptic plasticity in hippocampal slices. Collectively, these results suggest that α5 subunit-containing γ-aminobutyric acid type A receptors are novel targets for pharmacologic treatment of traumatic brain injury-induced persistent cognitive deficits.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
Khodaei S,Avramescu S,Wang DS,Sheng H,Chan NK,Lecker I,Fernandez-Escobar A,Lei G,Dewar MB,Whissell PD,Baker AJ,Orser BAdoi
10.1097/CCM.0000000000004161subject
Has Abstractpub_date
2020-04-01 00:00:00pages
533-544issue
4eissn
0090-3493issn
1530-0293pii
00003246-202004000-00012journal_volume
48pub_type
杂志文章abstract::Clinically, asystole or a bradyarrhythmia may follow countershock of ventricular fibrillation (VF) in up to 40% of attempts. This study evaluated the effects of artificial cardiac pacing, calcium chloride (CaCl2), and epinephrine in postcountershock asystole/bradycardia. Micromanometer catheters were positioned in the...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198509000-00001
更新日期:1985-09-01 00:00:00
abstract:OBJECTIVE:To describe the effects of inhaled prostacyclin administered after cardiopulmonary bypass (CPB) to a patient with severe pulmonary hypertension. DESIGN:Case report and literature review. SETTING:Cardiac surgical operating rooms and postoperative recovery unit. PATIENTS:A 63-yr-old female who had undergone ...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/00003246-200212000-00023
更新日期:2002-12-01 00:00:00
abstract:OBJECTIVE:Peripheral perfusion in critically ill patients frequently is assessed by use of clinical signs. Recently, the pulse oximetry signal has been suggested to reflect changes in peripheral perfusion. A peripheral perfusion index based on analysis of the pulse oximetry signal has been implemented in monitoring sys...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200206000-00006
更新日期:2002-06-01 00:00:00
abstract:OBJECTIVE:The administration of vasopressin during cardiopulmonary resuscitation (CPR) provides significantly more vital organ blood flow when compared with epinephrine during cardiac arrest in pigs. The effects of this potent vasoconstrictor on postresuscitation cardiovascular function remain unknown. The purpose of t...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199612000-00014
更新日期:1996-12-01 00:00:00
abstract::An 8-yr-old child suffered traumatic bilateral pneumothoraces and a ruptured right main bronchus. Surgical repair of the bronchus was postponed for 18 h after a definite diagnosis was established due to severe hypoxemia and hypercarbia. Only left endobronchial high-frequency ventilation with muscle relaxation correcte...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198712000-00019
更新日期:1987-12-01 00:00:00
abstract:OBJECTIVE:To determine the effects of stimulation of vascular dopaminergic receptor subtype 1 (dopamine-1) receptors in the renal and mesenteric vascular beds of a neonatal model. DESIGN:Prospective, unblinded, dose-response evaluation in an awake animal. SETTING:University research laboratory. SUBJECTS:Thirty newbo...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199610000-00018
更新日期:1996-10-01 00:00:00
abstract:OBJECTIVE:To evaluate the frequency and clinical correlates of ultrafilterable hypomagnesemia in neonates admitted to the neonatal intensive care unit (ICU). DESIGN:Prospective, observational study. SETTING:Massachusetts General Hospital and Mount Auburn Hospital. PATIENTS:A total of 117 patients (84 neonatal ICU pa...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199405000-00017
更新日期:1994-05-01 00:00:00
abstract:BACKGROUND:Hypertonic saline is the recommended therapy to shrink swollen brain cells in patients with acute hyponatremia accompanied by seizures. OBJECTIVES:In the absence of hypertonic saline, hypertonic mannitol will shrink the cell volume. Because mannitol is excreted rapidly, our aim was to ensure that it would b...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200006000-00037
更新日期:2000-06-01 00:00:00
abstract:OBJECTIVES:Preclinical studies reveal the neuroprotective properties of xenon, especially when combined with hypothermia. The purpose of this study was to investigate the feasibility and cardiac safety of inhaled xenon treatment combined with therapeutic hypothermia in out-of-hospital cardiac arrest patients. DESIGN:A...
journal_title:Critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1097/CCM.0b013e31828a4337
更新日期:2013-09-01 00:00:00
abstract:OBJECTIVES:Over-utilization of tests, treatments, and procedures is common for hospitalized patients in ICU settings. American Board of Internal Medicine Foundation's Choosing Wisely campaign tasked professional societies to identify sources of overuse in specialty care practice. The purpose of this study was to assess...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000003496
更新日期:2019-03-01 00:00:00
abstract::To understand better the incidence and meaning of hyperamylasemia in the intensive care setting, cellulose acetate membrane electrophoresis was used to measure the isoenzymes of serum amylase in 192 patients with a variety of critical illnesses. Seventy of these patients had elevated serum amylase levels, but none had...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198507000-00003
更新日期:1985-07-01 00:00:00
abstract::Hemodynamic effects of controlled mechanical ventilation (CMV), intermittent mandatory ventilation (IMV), and intermittent mandatory ventilation with 5 cm H20 PEEP (IMV 5 peep) were studied in 20 patients after aortocoronary bypass surgery. Significant increases in cardiac index (CI) and stroke volume index (SI) (p le...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198207000-00001
更新日期:1982-07-01 00:00:00
abstract:OBJECTIVE:To evaluate partial occlusion in patients with pulmonary hypertension with regard to a) the degree to which it leads to overestimation of pulmonary artery occlusion pressure (Ppao) and b) identification of factors that could enhance its recognition. DESIGN:Observational descriptive study. SETTING:Medical in...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200301000-00015
更新日期:2003-01-01 00:00:00
abstract::The effects of the Trendelenburg (TREND) position and passive straight leg raising (PLR) on cardiopulmonary performance in 18 anesthetized patients undergoing myocardial revascularization were studied with a two-dimensional transesophageal echocardiography probe and a thermodilution right ventricular ejection fraction...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00003246-198904000-00003
更新日期:1989-04-01 00:00:00
abstract:OBJECTIVE:Failure to detect clinical deterioration in the hospital is common and associated with poor patient outcomes and increased healthcare costs. Our objective was to evaluate the feasibility and accuracy of real-time risk stratification using the electronic Cardiac Arrest Risk Triage score, an electronic health r...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001716
更新日期:2016-08-01 00:00:00
abstract:OBJECTIVES:To determine the point prevalence of medication errors at the time of transition of care from an ICU to non-ICU location and assess error types and risk factors for medication errors during transition of care. DESIGN:This was a multicenter, retrospective, 7-day point prevalence study. SETTING:Fifty-eight I...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1097/CCM.0000000000003633
更新日期:2019-04-01 00:00:00
abstract:OBJECTIVES:To measure pulmonary capillary pressure and pulmonary artery occlusion pressures both during control conditions and during acute lung injury and to evaluate the effects of inotropic therapy and volume loading on these measurements after lung injury. DESIGN:Prospective, randomized, controlled laboratory tria...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200202000-00023
更新日期:2002-02-01 00:00:00
abstract:OBJECTIVES:Existing handheld glucose meters are glucose oxidase (GO)-based. Oxygen side reactions can introduce oxygen dependency, increase potential error, and limit clinical use. Our primary objectives were to: a) introduce a new glucose dehydrogenase (GD)-based electrochemical biosensor for point-of-care testing; b)...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1097/00003246-199803000-00036
更新日期:1998-03-01 00:00:00
abstract:BACKGROUND AND METHODS:The development of a multifactorial coagulopathy after massive transfusion is a well-recognized clinical problem that is almost always accompanied by hypothermia. The purpose of this study was to investigate the isolated effect of alterations of temperature on the integrity of the coagulation cas...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199210000-00007
更新日期:1992-10-01 00:00:00
abstract:OBJECTIVE:To assess the feasibility and safety of delivering early goal-directed sedation compared with standard sedation. DESIGN:Pilot prospective, multicenter, randomized, controlled trial. SETTING:Six ICUs. PATIENTS:Critically ill adults mechanically ventilated for greater than 24 hours. INTERVENTIONS:Patients r...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/CCM.0b013e31828a437d
更新日期:2013-08-01 00:00:00
abstract::Critical decreases in oxygen delivery (DO2) and mixed venous oxygen saturation (SvO2) are associated with anaerobic metabolism and, therefore, lactic acidosis. We studied 50 consecutive patients with sepsis and 50 consecutive patients with acute myocardial infarction (AMI) in whom the arterial blood lactate was greate...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198807000-00001
更新日期:1988-07-01 00:00:00
abstract:OBJECTIVE:To evaluate the accuracies of the respiratory rate/tidal volume ratio (rate/volume ratio), minute volume, and negative inspired force in predicting weaning outcome in postoperative mechanically ventilated patients. DESIGN:A prospective, observational study. SETTING:Surgical intensive care unit of a 270-bed ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199702000-00010
更新日期:1997-02-01 00:00:00
abstract:OBJECTIVE:To compare intraosseous with central venous blood samples for biochemical analyses and hemoglobin levels during cardiopulmonary resuscitation (CPR) and during cardiopulmonary resuscitation with infusion of sodium bicarbonate, epinephrine, and saline boluses through the intraosseous site. DESIGN:Prospective, ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199906000-00039
更新日期:1999-06-01 00:00:00
abstract:OBJECTIVE:To determine whether polymorphisms of the surfactant protein B gene may be associated with increased mortality in patients with the acute respiratory distress syndrome. DESIGN:A prospective cohort study. SETTING:Four adult intensive care units at a tertiary academic medical center. PATIENTS:Two hundred fou...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e318183f608
更新日期:2008-09-01 00:00:00
abstract::Subcutaneous, transcutaneous, and conjunctival oxygen tensions (PscO2, PtcO2, and PcjO2, respectively) were measured in anesthetized dogs subjected sequentially to normoxia, hyperoxia, and hypoxia. Intravascular pressure, hemodynamic and oxygen transport variables were measured simultaneously. PtcO2 and PcjO2 closely ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198812000-00011
更新日期:1988-12-01 00:00:00
abstract:OBJECTIVE:Heatstroke requires active body cooling and organ failure supportive care. Although heat waves are expected to recur over the next decades, little is known about the risk factors for mortality in heatstroke patients. We examined the prognosis and risk factors for hospital mortality in patients with heatstroke...
journal_title:Critical care medicine
pub_type: 评论,杂志文章,多中心研究
doi:10.1097/01.CCM.0000206469.33615.02
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVE:Pulmonary edema is a serious condition following brain injury of diverse etiologies, including large hemispheric infarctions. We have previously shown that treatment with hypertonic saline attenuates cerebral edema associated with experimental ischemic stroke. In a well-characterized animal model of large isc...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.ccm.0000150659.15558.23
更新日期:2005-01-01 00:00:00
abstract:OBJECTIVE:Leucine-rich repeat and immunoglobulin domain-containing protein (LINGO)-1 is expressed in neural stem cells, and its neutralization results in sustained neuronal immaturity. Thus, targeted inhibition of LINGO-1 via RNA interference may enhance transplanted neural stem cell survival and neuronal differentiati...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001351
更新日期:2016-03-01 00:00:00
abstract:OBJECTIVE:Cardiac surgery is frequently followed by postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. Currently, there are no recommendations for pharmacologic prevention of postoperative delirium. Impaired cholinergic transmission is believed to pla...
journal_title:Critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1097/CCM.0b013e31819da780
更新日期:2009-05-01 00:00:00
abstract:OBJECTIVE:Initial success with chimeric antigen receptor-modified T cell therapy for relapsed/refractory acute lymphoblastic leukemia is leading to expanded use through multicenter trials. Cytokine release syndrome, the most severe toxicity, presents a novel critical illness syndrome with limited data regarding diagnos...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002053
更新日期:2017-02-01 00:00:00