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1.
Eur J Radiol ; 144: 109989, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34627105

ABSTRACT

PURPOSE: To evaluate the prognostic value of left ventricular strains by cardiac magnetic resonance feature tracking (CMR-FT) in patients with re-perfused myocardial infarction (MI). METHODS: The study enrolled 58 patients with re-vascularized MI who underwent CMR within a week from acute MI. An 18-month follow-up was carried out for the composite endpoint of major adverse cardiovascular events (MACE). A 3 to 6-month post-MI ejection fraction (EF) was also measured. The predictive value of global longitudinal, circumferential, and radial strains (GLS, GCS, and GRS, respectively) for MACE and the follow-up EF was evaluated. RESULTS: All the global strains showed significant impairment in MACE positive cases (P < 0.05 for all). On univariate regression, MACE was reversely associated with early post-MI EF (OR: 0.90, 95% CI: 0.83-0.98, P: 0.01), and directly associated with GLS (OR: 1.32, 95% CI: 1.03-1.69, P: 0.02), GCS (OR: 1.23, 95% CI: 1.00-1.50, P: 0.04) and EDVI (OR:1.02, 95 %CI: 1.00-1.04, P: 0.01). On multivariate regression model, only the interaction between EF and GLS showed a significant association with MACE (OR[CI95%]: 1.1 [1.06-1.21]). EF < 30% and GLS > -8.9% had the highest sensitivity (78.9% and 89.5%, respectively) and specificity (45.2% and 54.8%, respectively) to predict MACE. The combination of EF < 30% and GLS > -8.9% increased the sensitivity to 94.7%. In addition, the cutoff values of 35.1% for early post-MI EF and -10% for GLS could identify patients with impaired follow-up EF with more than 80% sensitivity and specificity [AUC (CI95%): 0.893(0.76-1.00) for EF and AUC (CI95%):0.836(0.67-1,00) for GLS, P < 0.05 for both)]. CONCLUSIONS: GLS by CMR-FT is a powerful prognosticator of MACE and functional recovery in MI survivors, with incremental value added to early post-MI EF alone.


Subject(s)
Myocardial Infarction , Ventricular Function, Left , Heart , Humans , Magnetic Resonance Imaging, Cine , Magnetic Resonance Spectroscopy , Myocardial Infarction/diagnostic imaging , Myocardium , Predictive Value of Tests , Stroke Volume
2.
Radiol Med ; 126(8): 1074-1084, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33993441

ABSTRACT

Involvement of lymph nodes in patients with head and neck cancers impacts treatment and prognosis. Head and neck lymph nodes are comprised of superficial and deep groups which are interconnected. The deep lymph nodes, predominantly centered along internal jugular veins, are very well-known to radiologists and clinicians. However, superficial lymph nodes that drain lymph from the scalp, face, and neck are much less recognized. Here, we describe the anatomic and imaging features of these superficial lymph nodes on CT, MRI, and PET in oncologic settings.


Subject(s)
Head and Neck Neoplasms/pathology , Lymphatic Metastasis/diagnostic imaging , Multimodal Imaging , Aged , Aged, 80 and over , Face/diagnostic imaging , Female , Humans , Male , Middle Aged , Neck/diagnostic imaging
3.
Phys Med ; 84: 125-131, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33894582

ABSTRACT

PURPOSE: Optimization of CT scan practices can help achieve and maintain optimal radiation protection. The aim was to assess centering, scan length, and positioning of patients undergoing chest CT for suspected or known COVID-19 pneumonia and to investigate their effect on associated radiation doses. METHODS: With respective approvals from institutional review boards, we compiled CT imaging and radiation dose data from four hospitals belonging to four countries (Brazil, Iran, Italy, and USA) on 400 adult patients who underwent chest CT for suspected or known COVID-19 pneumonia between April 2020 and August 2020. We recorded patient demographics and volume CT dose index (CTDIvol) and dose length product (DLP). From thin-section CT images of each patient, we estimated the scan length and recorded the first and last vertebral bodies at the scan start and end locations. Patient mis-centering and arm position were recorded. Data were analyzed with analysis of variance (ANOVA). RESULTS: The extent and frequency of patient mis-centering did not differ across the four CT facilities (>0.09). The frequency of patients scanned with arms by their side (11-40% relative to those with arms up) had greater mis-centering and higher CTDIvol and DLP at 2/4 facilities (p = 0.027-0.05). Despite lack of variations in effective diameters (p = 0.14), there were significantly variations in scan lengths, CTDIvol and DLP across the four facilities (p < 0.001). CONCLUSIONS: Mis-centering, over-scanning, and arms by the side are frequent issues with use of chest CT in COVID-19 pneumonia and are associated with higher radiation doses.


Subject(s)
COVID-19 , Radiation Protection , Adult , Arm , Humans , Iran , Italy/epidemiology , Pandemics , Radiation Dosage , SARS-CoV-2
4.
Eur J Radiol ; 139: 109583, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33846041

ABSTRACT

PURPOSE: As of August 30th, there were in total 25.1 million confirmed cases and 845 thousand deaths caused by coronavirus disease of 2019 (COVID-19) worldwide. With overwhelming demands on medical resources, patient stratification based on their risks is essential. In this multi-center study, we built prognosis models to predict severity outcomes, combining patients' electronic health records (EHR), which included vital signs and laboratory data, with deep learning- and CT-based severity prediction. METHOD: We first developed a CT segmentation network using datasets from multiple institutions worldwide. Two biomarkers were extracted from the CT images: total opacity ratio (TOR) and consolidation ratio (CR). After obtaining TOR and CR, further prognosis analysis was conducted on datasets from INSTITUTE-1, INSTITUTE-2 and INSTITUTE-3. For each data cohort, generalized linear model (GLM) was applied for prognosis prediction. RESULTS: For the deep learning model, the correlation coefficient of the network prediction and manual segmentation was 0.755, 0.919, and 0.824 for the three cohorts, respectively. The AUC (95 % CI) of the final prognosis models was 0.85(0.77,0.92), 0.93(0.87,0.98), and 0.86(0.75,0.94) for INSTITUTE-1, INSTITUTE-2 and INSTITUTE-3 cohorts, respectively. Either TOR or CR exist in all three final prognosis models. Age, white blood cell (WBC), and platelet (PLT) were chosen predictors in two cohorts. Oxygen saturation (SpO2) was a chosen predictor in one cohort. CONCLUSION: The developed deep learning method can segment lung infection regions. Prognosis results indicated that age, SpO2, CT biomarkers, PLT, and WBC were the most important prognostic predictors of COVID-19 in our prognosis model.


Subject(s)
COVID-19 , Deep Learning , Electronic Health Records , Humans , Lung , Prognosis , SARS-CoV-2 , Tomography, X-Ray Computed
5.
NPJ Digit Med ; 4(1): 29, 2021 Feb 18.
Article in English | MEDLINE | ID: mdl-33603193

ABSTRACT

Coronavirus disease 2019 (Covid-19) is highly contagious with limited treatment options. Early and accurate diagnosis of Covid-19 is crucial in reducing the spread of the disease and its accompanied mortality. Currently, detection by reverse transcriptase-polymerase chain reaction (RT-PCR) is the gold standard of outpatient and inpatient detection of Covid-19. RT-PCR is a rapid method; however, its accuracy in detection is only ~70-75%. Another approved strategy is computed tomography (CT) imaging. CT imaging has a much higher sensitivity of ~80-98%, but similar accuracy of 70%. To enhance the accuracy of CT imaging detection, we developed an open-source framework, CovidCTNet, composed of a set of deep learning algorithms that accurately differentiates Covid-19 from community-acquired pneumonia (CAP) and other lung diseases. CovidCTNet increases the accuracy of CT imaging detection to 95% compared to radiologists (70%). CovidCTNet is designed to work with heterogeneous and small sample sizes independent of the CT imaging hardware. To facilitate the detection of Covid-19 globally and assist radiologists and physicians in the screening process, we are releasing all algorithms and model parameter details as open-source. Open-source sharing of CovidCTNet enables developers to rapidly improve and optimize services while preserving user privacy and data ownership.

6.
J Digit Imaging ; 34(2): 320-329, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33634416

ABSTRACT

To perform a multicenter assessment of the CT Pneumonia Analysis prototype for predicting disease severity and patient outcome in COVID-19 pneumonia both without and with integration of clinical information. Our IRB-approved observational study included consecutive 241 adult patients (> 18 years; 105 females; 136 males) with RT-PCR-positive COVID-19 pneumonia who underwent non-contrast chest CT at one of the two tertiary care hospitals (site A: Massachusetts General Hospital, USA; site B: Firoozgar Hospital Iran). We recorded patient age, gender, comorbid conditions, laboratory values, intensive care unit (ICU) admission, mechanical ventilation, and final outcome (recovery or death). Two thoracic radiologists reviewed all chest CTs to record type, extent of pulmonary opacities based on the percentage of lobe involved, and severity of respiratory motion artifacts. Thin-section CT images were processed with the prototype (Siemens Healthineers) to obtain quantitative features including lung volumes, volume and percentage of all-type and high-attenuation opacities (≥ -200 HU), and mean HU and standard deviation of opacities within a given lung region. These values are estimated for the total combined lung volume, and separately for each lung and each lung lobe. Multivariable analyses of variance (MANOVA) and multiple logistic regression were performed for data analyses. About 26% of chest CTs (62/241) had moderate to severe motion artifacts. There were no significant differences in the AUCs of quantitative features for predicting disease severity with and without motion artifacts (AUC 0.94-0.97) as well as for predicting patient outcome (AUC 0.7-0.77) (p > 0.5). Combination of the volume of all-attenuation opacities and the percentage of high-attenuation opacities (AUC 0.76-0.82, 95% confidence interval (CI) 0.73-0.82) had higher AUC for predicting ICU admission than the subjective severity scores (AUC 0.69-0.77, 95% CI 0.69-0.81). Despite a high frequency of motion artifacts, quantitative features of pulmonary opacities from chest CT can help differentiate patients with favorable and adverse outcomes.


Subject(s)
COVID-19 , Adult , Female , Humans , Lung/diagnostic imaging , Male , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Tomography, X-Ray Computed
7.
Med Image Anal ; 67: 101844, 2021 01.
Article in English | MEDLINE | ID: mdl-33091743

ABSTRACT

While image analysis of chest computed tomography (CT) for COVID-19 diagnosis has been intensively studied, little work has been performed for image-based patient outcome prediction. Management of high-risk patients with early intervention is a key to lower the fatality rate of COVID-19 pneumonia, as a majority of patients recover naturally. Therefore, an accurate prediction of disease progression with baseline imaging at the time of the initial presentation can help in patient management. In lieu of only size and volume information of pulmonary abnormalities and features through deep learning based image segmentation, here we combine radiomics of lung opacities and non-imaging features from demographic data, vital signs, and laboratory findings to predict need for intensive care unit (ICU) admission. To our knowledge, this is the first study that uses holistic information of a patient including both imaging and non-imaging data for outcome prediction. The proposed methods were thoroughly evaluated on datasets separately collected from three hospitals, one in the United States, one in Iran, and another in Italy, with a total 295 patients with reverse transcription polymerase chain reaction (RT-PCR) assay positive COVID-19 pneumonia. Our experimental results demonstrate that adding non-imaging features can significantly improve the performance of prediction to achieve AUC up to 0.884 and sensitivity as high as 96.1%, which can be valuable to provide clinical decision support in managing COVID-19 patients. Our methods may also be applied to other lung diseases including but not limited to community acquired pneumonia. The source code of our work is available at https://github.com/DIAL-RPI/COVID19-ICUPrediction.


Subject(s)
COVID-19/diagnostic imaging , Intensive Care Units/statistics & numerical data , Patient Admission/statistics & numerical data , Pneumonia, Viral/diagnostic imaging , Adult , Aged , COVID-19/epidemiology , Datasets as Topic , Disease Progression , Female , Humans , Iran/epidemiology , Italy/epidemiology , Male , Middle Aged , Predictive Value of Tests , Prognosis , SARS-CoV-2 , United States/epidemiology
8.
IEEE J Biomed Health Inform ; 24(12): 3529-3538, 2020 12.
Article in English | MEDLINE | ID: mdl-33044938

ABSTRACT

Early and accurate diagnosis of Coronavirus disease (COVID-19) is essential for patient isolation and contact tracing so that the spread of infection can be limited. Computed tomography (CT) can provide important information in COVID-19, especially for patients with moderate to severe disease as well as those with worsening cardiopulmonary status. As an automatic tool, deep learning methods can be utilized to perform semantic segmentation of affected lung regions, which is important to establish disease severity and prognosis prediction. Both the extent and type of pulmonary opacities help assess disease severity. However, manually pixel-level multi-class labelling is time-consuming, subjective, and non-quantitative. In this article, we proposed a hybrid weak label-based deep learning method that utilize both the manually annotated pulmonary opacities from COVID-19 pneumonia and the patient-level disease-type information available from the clinical report. A UNet was firstly trained with semantic labels to segment the total infected region. It was used to initialize another UNet, which was trained to segment the consolidations with patient-level information using the Expectation-Maximization (EM) algorithm. To demonstrate the performance of the proposed method, multi-institutional CT datasets from Iran, Italy, South Korea, and the United States were utilized. Results show that our proposed method can predict the infected regions as well as the consolidation regions with good correlation to human annotation.


Subject(s)
COVID-19/diagnostic imaging , Deep Learning , Tomography, X-Ray Computed/methods , Algorithms , COVID-19/virology , Female , Humans , Male , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index
9.
PLoS One ; 15(9): e0239519, 2020.
Article in English | MEDLINE | ID: mdl-32970733

ABSTRACT

The new coronavirus disease 2019 (COVID-19) pandemic has challenged many healthcare systems around the world. While most of the current understanding of the clinical features of COVID-19 is derived from Chinese studies, there is a relative paucity of reports from the remaining global health community. In this study, we analyze the clinical and radiologic factors that correlate with mortality odds in COVID-19 positive patients from a tertiary care center in Tehran, Iran. A retrospective cohort study of 90 patients with reverse transcriptase-polymerase chain reaction (RT-PCR) positive COVID-19 infection was conducted, analyzing demographics, co-morbidities, presenting symptoms, vital signs, laboratory values, chest radiograph findings, and chest CT features based on mortality. Chest radiograph was assessed using the Radiographic Assessment of Lung Edema (RALE) scoring system. Chest CTs were assessed according to the opacification pattern, distribution, and standardized severity score. Initial and follow-up Chest CTs were compared if available. Multiple logistic regression was used to generate a prediction model for mortality. The 90 patients included 59 men and 31 women (59.4 ± 16.6 years), including 21 deceased and 69 surviving patients. Among clinical features, advanced age (p = 0.02), low oxygenation saturation (p<0.001), leukocytosis (p = 0.02), low lymphocyte fraction (p = 0.03), and low platelet count (p = 0.048) were associated with increased mortality. High RALE score on initial chest radiograph (p = 0.002), presence of pleural effusions on initial CT chest (p = 0.005), development of pleural effusions on follow-up CT chest (p = 0.04), and worsening lung severity score on follow-up CT Chest (p = 0.03) were associated with mortality. A two-factor logistic model using patient age and oxygen saturation was created, which demonstrates 89% accuracy and area under the ROC curve of 0.86 (p<0.0001). Specific demographic, clinical, and imaging features are associated with increased mortality in COVID-19 infections. Attention to these features can help optimize patient management.


Subject(s)
Coronavirus Infections/diagnostic imaging , Coronavirus Infections/mortality , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/mortality , Adult , Aged , Betacoronavirus , COVID-19 , Comorbidity , Female , Humans , Image Processing, Computer-Assisted , Iran , Logistic Models , Male , Middle Aged , Pandemics , Radiography, Thoracic , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Tertiary Care Centers , Tomography, X-Ray Computed
10.
J Comput Assist Tomogr ; 44(5): 640-646, 2020.
Article in English | MEDLINE | ID: mdl-32842058

ABSTRACT

PURPOSE: This study aimed to assess if computed tomography (CT) radiomics can predict the severity and outcome of patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: This institutional ethical board-approved study included 92 patients (mean age, 59 ± 17 years; 57 men, 35 women) with positive reverse transcription polymerase chain reaction assay for COVID-19 infection who underwent noncontrast chest CT. Two radiologists evaluated all chest CT examinations and recorded opacity type, distribution, and extent of lobar involvement. Information on symptom duration before hospital admission, the period of hospital admission, presence of comorbid conditions, laboratory data, and outcomes (recovery or death) was obtained from the medical records. The entire lung volume was segmented on thin-section Digital Imaging and Communication in Medicine images to derive whole-lung radiomics. Data were analyzed using multiple logistic regression with receiver operator characteristic area under the curve (AUC) as the output. RESULTS: Computed tomography radiomics (AUC, 0.99) outperformed clinical variables (AUC, 0.89) for prediction of the extent of pulmonary opacities related to COVID-19 pneumonia. Type of pulmonary opacities could be predicted with CT radiomics (AUC, 0.77) but not with clinical or laboratory data (AUC, <0.56; P > 0.05). Prediction of patient outcome with radiomics (AUC, 0.85) improved to an AUC of 0.90 with the addition of clinical variables (patient age and duration of presenting symptoms before admission). Among clinical variables, the combination of peripheral capillary oxygen saturation on hospital admission, duration of symptoms, platelet counts, and patient age provided an AUC of 0.81 for predicting patient outcomes. CONCLUSIONS: Radiomics from noncontrast CT reliably predict disease severity (AUC, 0.99) and outcome (AUC, 0.85) in patients with COVID-19 pneumonia.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Lung/diagnostic imaging , Pneumonia, Viral/diagnosis , Tomography, X-Ray Computed/methods , COVID-19 , Disease Progression , Female , Humans , Male , Middle Aged , Pandemics , Predictive Value of Tests , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
11.
ArXiv ; 2020 Sep 16.
Article in English | MEDLINE | ID: mdl-32743020

ABSTRACT

While image analysis of chest computed tomography (CT) for COVID-19 diagnosis has been intensively studied, little work has been performed for image-based patient outcome prediction. Management of high-risk patients with early intervention is a key to lower the fatality rate of COVID-19 pneumonia, as a majority of patients recover naturally. Therefore, an accurate prediction of disease progression with baseline imaging at the time of the initial presentation can help in patient management. In lieu of only size and volume information of pulmonary abnormalities and features through deep learning based image segmentation, here we combine radiomics of lung opacities and non-imaging features from demographic data, vital signs, and laboratory findings to predict need for intensive care unit (ICU) admission. To our knowledge, this is the first study that uses holistic information of a patient including both imaging and non-imaging data for outcome prediction. The proposed methods were thoroughly evaluated on datasets separately collected from three hospitals, one in the United States, one in Iran, and another in Italy, with a total 295 patients with reverse transcription polymerase chain reaction (RT-PCR) assay positive COVID-19 pneumonia. Our experimental results demonstrate that adding non-imaging features can significantly improve the performance of prediction to achieve AUC up to 0.884 and sensitivity as high as 96.1%, which can be valuable to provide clinical decision support in managing COVID-19 patients. Our methods may also be applied to other lung diseases including but not limited to community acquired pneumonia. The source code of our work is available at https://github.com/DIAL-RPI/COVID19-ICUPrediction.

12.
Radiol Cardiothorac Imaging ; 2(4): e200322, 2020 Aug.
Article in English | MEDLINE | ID: mdl-33778612

ABSTRACT

PURPOSE: To compare prediction of disease outcome, severity, and patient triage in coronavirus disease 2019 (COVID-19) pneumonia with whole lung radiomics, radiologists' interpretation, and clinical variables. MATERIALS AND METHODS: This institutional review board-approved retrospective study included 315 adult patients (mean age, 56 years [range, 21-100 years], 190 men, 125 women) with COVID-19 pneumonia who underwent noncontrast chest CT. All patients (inpatients, n = 210; outpatients, n = 105) were followed-up for at least 2 weeks to record disease outcome. Clinical variables, such as presenting symptoms, laboratory data, peripheral oxygen saturation, and comorbid diseases, were recorded. Two radiologists assessed each CT in consensus and graded the extent of pulmonary involvement (by percentage of involved lobe) and type of opacities within each lobe. Radiomics were obtained for the entire lung, and multiple logistic regression analyses with areas under the curve (AUCs) as outputs were performed. RESULTS: Most patients (276/315, 88%) recovered from COVID-19 pneumonia; 36/315 patients (11%) died, and 3/315 patients (1%) remained admitted in the hospital. Radiomics differentiated chest CT in outpatient versus inpatient with an AUC of 0.84 (P < .005), while radiologists' interpretations of disease extent and opacity type had an AUC of 0.69 (P < .0001). Whole lung radiomics were superior to the radiologists' interpretation for predicting patient outcome in terms of intensive care unit (ICU) admission (AUC: 0.75 vs 0.68) and death (AUC: 0.81 vs 0.68) (P < .002). The addition of clinical variables to radiomics improved the AUC to 0.84 for predicting ICU admission. CONCLUSION: Radiomics from noncontrast chest CT were superior to radiologists' assessment of extent and type of pulmonary opacities in predicting COVID-19 pneumonia outcome, disease severity, and patient triage.© RSNA, 2020.

13.
Pharmacol Biochem Behav ; 103(2): 313-21, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22944106

ABSTRACT

INTRODUCTION: Pioglitazone, a PPAR-γ agonist, which is clinically used in treating diabetic patients, has been recently reported to have crucial roles in improving cognition and memory performance. Since the mechanisms involved in the neuroprotective effect of pioglitazone are not entirely understood, the current study was designed to investigate the possible interaction of pioglitazone with morphine in memory-impaired mice and the probable role of nitric oxide (NO) in this effect. MATERIALS AND METHODS: All the experiments were performed in passive avoidance and Y-maze paradigms. To induce memory impairment, mice were administered morphine (1, 3 and 10mg/kg, s.c.) immediately before the training trial. Pioglitazone (20, 40 and 80mg/kg, p.o.) was gavaged 2h prior to the training trial. Further, an NO synthase inhibitor, L-NAME (10mg/kg, i.p.), or an inducible NO synthase inhibitor, aminoguanidine (100mg/kg, i.p.) was administered 30 min before the training trial to determine the possible involvement of NO in the restorative effect of pioglitazone. RESULTS: 1) Morphine dose dependently impaired the acquisition of spatial memory and passive avoidance task. 2) Treatment with pioglitazone significantly improved the memory performance in morphine-treated mice in both tests. 3) In the passive avoidance task, L-NAME, but not aminoguanidine, altered the effect of pioglitazone on morphine-induced memory impairment. 4) In Y-maze discrimination, the memory improving effect of pioglitazone was reversed by both NO synthase inhibitors, L-NAME and aminoguanidine. DISCUSSION: Our results demonstrate that the pioglitazone improving effect on the morphine-induced impairment of memory acquisition is at least in part through the NO pathway. It is suggested that in short term spatial recognition memory, both inducible and constitutive NO synthases are involved, but in the long term fear memory, only the constitutive NO synthases indicated a prominent role in the anti-amnestic effect of pioglitazone on morphine-induced memory impairment.


Subject(s)
Memory Disorders/drug therapy , Morphine/adverse effects , Nitric Oxide/physiology , Thiazolidinediones/therapeutic use , Animals , Avoidance Learning , Dose-Response Relationship, Drug , Fear , Male , Maze Learning , Memory Disorders/chemically induced , Mice , NG-Nitroarginine Methyl Ester/pharmacology , Pioglitazone
14.
Behav Brain Res ; 231(1): 138-45, 2012 May 16.
Article in English | MEDLINE | ID: mdl-22440233

ABSTRACT

INTRODUCTION: Pioglitazone, a peroxisome proliferator activated receptor γ (PPARγ) agonist, is widely used in clinical medicine as a treatment for type 2 diabetes and is recently proved to have beneficial effects on improving cognition in early stages of Alzheimer's disease (AD). Moreover, it has been shown that pioglitazone reduces N-methyl-D-aspartate (NMDA, a glutamate agonist) mediated calcium currents and transients. Since enhanced calcium transients are present in AD models, we tested the hypothesis whether pioglitazone manifests its acquisition memory enhancement role through glutamatergic pathway. MATERIAL AND METHODS: Memory performance was evaluated in a two-trial recognition Y-maze test and passive avoidance in mice. Pioglitazone (20 or 40 mg/kg, p.o.) was administered 2h before each trial, NMDA (75 mg/kg i.p.), 15 min before pioglitazone, and scopolamine, an M1 (muscarinic) receptor antagonist (0.3 or 1.0 mg/kg i.p.) and MK-801 (dizocilpine) (0.01, 0.03 or 0.1 mg/kg, i.p.), the highly selective, non-competitive NMDA antagonist--30 min beforehand. RESULTS: (1) We induced the memory impairment by scopolamine or MK-801 before trials. (2) Pioglitazone did not improve the memory impairment induced by MK-801. (3) Pioglitazone significantly improved the memory impairment induced by scopolamine. (4) Subeffective dose of MK-801 nullified the beneficial effects of pioglitazone in scopolamine induced memory impaired mice. (5) NMDA promoted the effects of subeffective dose of pioglitazone on memory impaired by scopolamine. DISCUSSION: In conclusion, the present study suggests that glutamatergic pathway is involved in the pioglitazone induced memory performance.


Subject(s)
Hypoglycemic Agents/therapeutic use , Memory Disorders/drug therapy , Memory/drug effects , Receptors, N-Methyl-D-Aspartate/metabolism , Scopolamine/pharmacology , Thiazolidinediones/therapeutic use , Animals , Avoidance Learning/drug effects , Dizocilpine Maleate/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Hypoglycemic Agents/pharmacology , Maze Learning/drug effects , Memory Disorders/chemically induced , Memory Disorders/metabolism , Mice , Muscarinic Antagonists/pharmacology , Pioglitazone , Thiazolidinediones/pharmacology
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