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1.
Front Neurol ; 14: 1217796, 2023.
Article de Anglais | MEDLINE | ID: mdl-37941573

RÉSUMÉ

Background: Rapid and accurate triage of acute ischemic stroke (AIS) is essential for early revascularization and improved patient outcomes. Response to acute reperfusion therapies varies significantly based on patient-specific cerebrovascular anatomy that governs cerebral blood flow. We present an end-to-end machine learning approach for automatic stroke triage. Methods: Employing a validated convolutional neural network (CNN) segmentation model for image processing, we extract each patient's cerebrovasculature and its morphological features from baseline non-invasive angiography scans. These features are used to detect occlusion's presence and the site automatically, and for the first time, to estimate collateral circulation without manual intervention. We then use the extracted cerebrovascular features along with commonly used clinical and imaging parameters to predict the 90 days functional outcome for each patient. Results: The CNN model achieved a segmentation accuracy of 94% based on the Dice similarity coefficient (DSC). The automatic stroke detection algorithm had a sensitivity and specificity of 92% and 94%, respectively. The models for occlusion site detection and automatic collateral grading reached 96% and 87.2% accuracy, respectively. Incorporating the automatically extracted cerebrovascular features significantly improved the 90 days outcome prediction accuracy from 0.63 to 0.83. Conclusion: The fast, automatic, and comprehensive model presented here can improve stroke diagnosis, aid collateral assessment, and enhance prognostication for treatment decisions, using cerebrovascular morphology.

3.
ASAIO J ; 68(12): 1419-1427, 2022 12 01.
Article de Anglais | MEDLINE | ID: mdl-35593878

RÉSUMÉ

Extracorporeal membrane oxygenation (ECMO) is an increasingly utilized intervention for cardiopulmonary failure. Analgosedation during ECMO support is essential to ensure adequate pain and agitation control and ventilator synchrony, optimize ECMO support, facilitate patient assessment, and minimize adverse events. Although the principles of analgosedation are likely similar for all critically ill patients, ECMO circuitry alters medication pharmacodynamics and pharmacokinetics. The lack of clinical guidelines for analgosedation during ECMO, especially at times of medication shortage, can affect patient management. Here, we review pharmacological considerations, protocols, and special considerations for analgosedation in critically ill adults receiving ECMO support.


Sujet(s)
Oxygénation extracorporelle sur oxygénateur à membrane , Adulte , Humains , Oxygénation extracorporelle sur oxygénateur à membrane/effets indésirables , Oxygénation extracorporelle sur oxygénateur à membrane/méthodes , Maladie grave/thérapie
4.
J Stroke Cerebrovasc Dis ; 30(11): 106059, 2021 Nov.
Article de Anglais | MEDLINE | ID: mdl-34464927

RÉSUMÉ

Several clinical trials have demonstrated that advanced neuroimaging can select patients for recanalization therapy in an extended time window. The favorable functional outcomes and safety profile of these studies have led to the incorporation of neuroimaging in endovascular treatment guidelines, and most recently, also extended to decision making on thrombolysis. Two randomized clinical trials have demonstrated that patients who are not amenable to endovascular thrombectomy within 4.5 hours from symptoms discovery or beyond 4.5 hours from the last-known-well time may also be safely treated with intravenous thrombolysis and have a clinical benefit above the risk of safety concerns. With the growing aging population, increased stroke incidence in the young, and the impact of evolving medical practice, healthcare and stroke systems of care need to adapt continuously to provide evidence-based care efficiently. Therefore, understanding and incorporating appropriate screening strategies is critical for the prompt recognition of potentially eligible patients for extended-window intravenous thrombolysis. Here we review the clinical trial evidence for thrombolysis for acute ischemic stroke in the extended time window and provide a review of new enrolling clinical trials that include thrombolysis intervention beyond the 4.5 hour window.


Sujet(s)
Accident vasculaire cérébral ischémique , Traitement thrombolytique , Délai jusqu'au traitement , Fibrinolytiques/administration et posologie , Humains , Accident vasculaire cérébral ischémique/traitement médicamenteux , Essais contrôlés randomisés comme sujet , Délai jusqu'au traitement/statistiques et données numériques , Résultat thérapeutique
5.
Semin Neurol ; 41(4): 411-421, 2021 08.
Article de Anglais | MEDLINE | ID: mdl-33851393

RÉSUMÉ

The use of left ventricular assist devices (LVADs) has been increasing in the last decade, along with the number of patients with advanced heart failure refractory to medical therapy. Ischemic stroke and intracranial hemorrhage remain the leading causes of morbidity and mortality in LVAD patients. Despite the common occurrence and the significant outcome impact, underlying mechanisms and management strategies of stroke in LVAD patients are controversial. In this article, we review our current knowledge on pathophysiology and risk factors of LVAD-associated stroke, outline the diagnostic approach, and discuss treatment strategies.


Sujet(s)
Défaillance cardiaque , Dispositifs d'assistance circulatoire , Accident vasculaire cérébral , Défaillance cardiaque/étiologie , Défaillance cardiaque/thérapie , Dispositifs d'assistance circulatoire/effets indésirables , Humains , Facteurs de risque , Accident vasculaire cérébral/étiologie , Accident vasculaire cérébral/thérapie
7.
J Stroke Cerebrovasc Dis ; 29(12): 105344, 2020 Dec.
Article de Anglais | MEDLINE | ID: mdl-33049464

RÉSUMÉ

BACKGROUND/OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on hospital admissions and outcomes in patients admitted with acute ischemic stroke. METHODS: Single-center retrospective analysis of patients admitted to the hospital with acute ischemic stroke, between December 1st, 2019 and June 30th, 2020. Outcomes were classified as none-to-minimal disability, moderate-to-severe disability, and death based on discharge disposition, and compared between two time periods: pre-COVID-19 era (December 1st, 2019 to March 11th, 2020) and COVID-19 era (March 12th to June 30th, 2020). We also performed a comparative trend analysis for the equivalent period between 2019 and 2020. RESULTS: Five hundred and seventy-five patients with a mean age (years±SD) of 68±16 were admitted from December 1st, 2019 to June 30th, 2020, with a clinical diagnosis of acute ischemic stroke. Of these, 255 (44.3%) patients were admitted during the COVID-19 era. We observed a 22.1% and 39.5% decline in admission for acute ischemic stroke in April and May 2020, respectively. A significantly higher percentage of patients with acute ischemic stroke received intravenous thrombolysis during the COVID-19 era (p = 0.020). In patients with confirmed COVID-19, we found a higher percentage of older men with preexisting comorbidities such as hyperlipidemia, coronary artery disease, and diabetes mellitus but a lower rate of atrial fibrillation. In addition, we found a treatment delay in both intravenous thrombolysis (median 94.5 min versus 38 min) and mechanical thrombectomy (median 244 min versus 86 min) in patients with confirmed COVID-19 infection. There were no differences in patients' disposition including home, short-term, and long-term facility (p = 0.60). CONCLUSIONS: We observed a reduction of hospital admissions in acute ischemic strokes and some delay in reperfusion therapy during the COVID-19 pandemic. Prospective studies and a larger dataset analysis are warranted.


Sujet(s)
Encéphalopathie ischémique/thérapie , COVID-19 , Hospitalisation/tendances , Évaluation des résultats et des processus en soins de santé/tendances , Accident vasculaire cérébral/thérapie , Thrombectomie/tendances , Traitement thrombolytique/tendances , Délai jusqu'au traitement/tendances , Sujet âgé , Sujet âgé de 80 ans ou plus , Encéphalopathie ischémique/diagnostic , Encéphalopathie ischémique/mortalité , Services de santé communautaires/tendances , Femelle , Mortalité hospitalière , Humains , Mâle , Adulte d'âge moyen , Récupération fonctionnelle , Études rétrospectives , Accident vasculaire cérébral/diagnostic , Accident vasculaire cérébral/mortalité , Centres de soins tertiaires/tendances , Facteurs temps , Résultat thérapeutique , Virginie
8.
Stroke ; 50(7): 1688-1695, 2019 07.
Article de Anglais | MEDLINE | ID: mdl-31177984

RÉSUMÉ

Background and Purpose- We investigated the prognostic significance of spontaneous intracerebral hemorrhage location in presence of severe intraventricular hemorrhage. Methods- We analyzed diagnostic computed tomography scans from 467/500 (excluding primary intraventricular hemorrhage) subjects from the CLEAR (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) III trial. We measured intracerebral hemorrhage engagement with specific anatomic regions, and estimated association of each region with blinded assessment of dichotomized poor stroke outcomes: mortality, modified Rankin Scale score of 4 to 6, National Institutes of Health Stroke Scale score of >4, stroke impact scale score of <60, Barthel Index <86, and EuroQol visual analogue scale score of <50 and <70 at days 30 and 180, respectively, using logistic regression models. Results- Frequency of anatomic region involvement consisted of thalamus (332 lesions, 71.1% of subjects), caudate (219, 46.9%), posterior limb internal capsule (188, 40.3%), globus pallidus/putamen (127, 27.2%), anterior limb internal capsule (108, 23.1%), and lobar (29, 6.2%). Thalamic location was independently associated with mortality (days 30 and 180) and with poor outcomes on most stroke scales at day 180 on adjusted analysis. Posterior limb internal capsule and globus pallidus/putamen involvement was associated with increased odds of worse disability at days 30 and 180. Anterior limb internal capsule and caudate locations were associated with decreased mortality on days 30 and 180. Anterior limb internal capsule lesions were associated with decreased long-term morbidity. Conclusions- Acute intracerebral hemorrhage lesion topography provides important insights into anatomic correlates of mortality and functional outcomes even in severe intraventricular hemorrhage causing obstructive hydrocephalus. Models accounting for intracerebral hemorrhage location in addition to volumes may improve outcome prediction and permit stratification of benefit from aggressive acute interventions. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00784134.


Sujet(s)
Hémorragie cérébrale/imagerie diagnostique , Ventricules cérébraux/imagerie diagnostique , Sujet âgé , Noyaux gris centraux/imagerie diagnostique , Hémorragie cérébrale/mortalité , Hémorragie cérébrale/thérapie , Études de cohortes , Femelle , Échelle de coma de Glasgow , Globus pallidus/imagerie diagnostique , Humains , Hydrocéphalie/étiologie , Mâle , Adulte d'âge moyen , Pronostic , Études prospectives , Thalamus/imagerie diagnostique , Tomodensitométrie , Résultat thérapeutique
9.
Neurocrit Care ; 30(2): 380-386, 2019 04.
Article de Anglais | MEDLINE | ID: mdl-30251074

RÉSUMÉ

INTRODUCTION: The Clot Lysis: Evaluating Accelerated Resolution of IVH trial examined whether irrigating the ventricular system with alteplase improved functional outcomes in patients with small intracerebral hemorrhage (ICH) and large intraventricular hemorrhage (IVH). Thalamic ICH location was common and was associated with poor outcome. One possible explanation is thalamic ICH-associated mass effect obstructing the third ventricle. We hypothesized that patients with thalamic ICH obstructing the third ventricle would have worse functional outcomes compared to patients without obstructing lesions. METHODS: ICH obstruction of third ventricle was defined as third ventricle compression on 1 or more axial computed tomography slices visually impeding cerebral spinal fluid flow. If the third ventricle was casted with IVH, it was scored as such. Multivariable logistic regression analyses were used to determine whether obstruction of the third ventricle predicts poor functional outcomes defined as modified Rankin score (mRS) 4-6, higher mRS, and mortality at 180 days. Models were adjusted for thalamic ICH location, ICH volume, IVH volume, age, hydrocephalus, baseline Glasgow coma scale, and percentage of low cerebral perfusion pressures during treatment. RESULTS: Among saline-treated patients, obstruction of the third ventricle by IVH was a significant predictor of higher mRS at 180 days (OR 1.87, CI 1.01-3.47) and mortality at 180 days (OR 2.73, CI 1.27-5.87) while obstruction by ICH was not. In contrast, among alteplase-treated patients, obstruction by ICH was a significant predictor of mRS 4-6 (OR 3.20, CI 1.30-7.88) and higher mRS at 180 days (OR 2.33, CI 1.24-4.35), while obstruction by IVH was not. CONCLUSIONS: Poor outcomes were associated with mass-related obstruction of the third ventricle from thalamic ICH in alteplase-treated patients and from IVH in saline-treated patients. Once the ventricular system is cleared with alteplase, obstruction of cerebral spinal fluid flow from thalamic ICH might become important in functional recovery.


Sujet(s)
Hémorragie cérébrale/traitement médicamenteux , Fibrinolytiques/administration et posologie , , Thalamus/anatomopathologie , Troisième ventricule/anatomopathologie , Activateur tissulaire du plasminogène/administration et posologie , Adulte , Sujet âgé , Hémorragie cérébrale/imagerie diagnostique , Hémorragie cérébrale intraventriculaire/traitement médicamenteux , Femelle , Humains , Mâle , Adulte d'âge moyen , Thalamus/imagerie diagnostique , Troisième ventricule/imagerie diagnostique
10.
Neurocrit Care ; 30(2): 364-371, 2019 04.
Article de Anglais | MEDLINE | ID: mdl-30397844

RÉSUMÉ

BACKGROUND/OBJECTIVE: Prompt treatment of acute intracranial hypertension is vital to preserving neurological function and frequently includes administration of 23.4% NaCl. However, 23.4% NaCl administration requires central venous catheterization that can delay treatment. Intraosseous catheterization is an alternative route of venous access that may result in more rapid administration of 23.4% NaCl. METHODS: Single-center retrospective analysis of 76 consecutive patients, between January 2015 and January 2018, with clinical signs of intracranial hypertension received 23.4% NaCl through either central venous catheter or intraosseous access. RESULTS: Intraosseous cannulation was successful on the first attempt in 97% of patients. No immediate untoward effects were seen with intraosseous cannulation. Time to treatment with 23.4% NaCl was significantly shorter in patients with intraosseous access compared to central venous catheter (p < 0.0001). CONCLUSIONS: Intraosseous cannulation resulted in more rapid administration of 23.4% NaCl with no immediate serious complications. Further investigations to identify the clinical benefits and safety of hypertonic medication administration via intraosseous cannulation are warranted.


Sujet(s)
Voies veineuses centrales , Perfusions intraosseuses , Hypertension intracrânienne/thérapie , , Solution saline hypertonique/administration et posologie , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Études rétrospectives
11.
Brain Circ ; 4(1): 1-13, 2018.
Article de Anglais | MEDLINE | ID: mdl-30276330

RÉSUMÉ

The cessation (ischemia) and restoration (reperfusion) of cerebral blood flow after cardiac arrest (CA) induce inflammatory processes that can result in additional brain injury. Therapeutic hypothermia (TH) has been proven as a brain protective strategy after CA. In this article, the underlying pathophysiology of ischemia-reperfusion brain injury with emphasis on the role of inflammatory mechanisms is reviewed. Potential targets for immunomodulatory treatments and relevant effects of TH are also discussed. Further studies are needed to delineate the complex pathophysiology and interactions among different components of immune response after CA and identify appropriate targets for clinical investigations.

12.
Crit Care ; 22(1): 153, 2018 Jun 07.
Article de Anglais | MEDLINE | ID: mdl-29880020

RÉSUMÉ

BACKGROUND: The incidence of seizures in intensive care units ranges from 3.3% to 34%. It is therefore often necessary to initiate or continue anticonvulsant drugs in this setting. When a new anticonvulsant is initiated, drug factors, such as onset of action and side effects, and patient factors, such as age, renal, and hepatic function, should be taken into account. It is important to note that the altered physiology of critically ill patients as well as pharmacological and nonpharmacological interventions such as renal replacement therapy, extracorporeal membrane oxygenation, and target temperature management may lead to therapeutic failure or toxicity. This may be even more challenging with the availability of newer antiepileptics where the evidence for their use in critically ill patients is limited. MAIN BODY: This article reviews the pharmacokinetics and pharmacodynamics of antiepileptics as well as application of these principles when dosing antiepileptics and monitoring serum levels in critically ill patients. The selection of the most appropriate anticonvulsant to treat seizure and status epileptics as well as the prophylactic use of these agents in this setting are also discussed. Drug-drug interactions and the effect of nonpharmacological interventions such as renal replacement therapy, plasma exchange, and extracorporeal membrane oxygenation on anticonvulsant removal are also included. CONCLUSION: Optimal management of antiepileptic drugs in the intensive care unit is challenging given altered physiology, polypharmacy, and nonpharmacological interventions, and requires a multidisciplinary approach where appropriate and timely assessment, diagnosis, treatment, and monitoring plans are in place.


Sujet(s)
Anticonvulsivants/usage thérapeutique , Maladie grave/thérapie , Biodisponibilité , Période , Humains , Unités de soins intensifs/organisation et administration , Unités de soins intensifs/tendances , Métabolisme/physiologie , Liaison aux protéines
13.
Neurocrit Care ; 29(2): 225-232, 2018 10.
Article de Anglais | MEDLINE | ID: mdl-29637518

RÉSUMÉ

BACKGROUND: Cerebrovascular events (CVE) are among the most common and serious complications after implantation of continuous-flow left ventricular assist devices (CF-LVAD). We studied the incidence, subtypes, anatomical distribution, and pre- and post-implantation risk factors of CVEs as well as the effect of CVEs on outcomes after CF-LVAD implantation at our institution. METHODS: Retrospective analysis of clinical and neuroimaging data of 372 patients with CF-LVAD between May 2005 and December 2013 using standard statistical methods. RESULTS: CVEs occurred in 71 patients (19%), consisting of 35 ischemic (49%), 26 hemorrhagic (37%), and 10 ischemic+hemorrhagic (14%) events. History of coronary artery disease and female gender was associated with higher odds of ischemic CVE (OR 2.84 and 2.5, respectively), and diabetes mellitus was associated with higher odds of hemorrhagic CVE (OR 3.12). While we found a higher rate of ischemic CVEs in patients not taking any antithrombotic medications, no difference was found between patients with ischemic and hemorrhagic CVEs. Occurrence of CVEs was associated with increased mortality (HR 1.62). Heart transplantation was associated with improved survival (HR 0.02). In patients without heart transplantation, occurrence of CVE was associated with decreased survival. CONCLUSIONS: LVADs are associated with high rates of CVE, increased mortality, and lower rates of heart transplantation. Further investigations to identify the optimal primary and secondary stroke prevention measures in post-LVAD patients are warranted.


Sujet(s)
Encéphalopathie ischémique , Défaillance cardiaque , Transplantation cardiaque , Dispositifs d'assistance circulatoire , Hémorragies intracrâniennes , Accident vasculaire cérébral , Sujet âgé , Encéphalopathie ischémique/étiologie , Encéphalopathie ischémique/mortalité , Femelle , Défaillance cardiaque/mortalité , Défaillance cardiaque/thérapie , Transplantation cardiaque/statistiques et données numériques , Dispositifs d'assistance circulatoire/effets indésirables , Dispositifs d'assistance circulatoire/statistiques et données numériques , Humains , Hémorragies intracrâniennes/étiologie , Hémorragies intracrâniennes/mortalité , Mâle , Adulte d'âge moyen , Facteurs de risque , Accident vasculaire cérébral/étiologie , Accident vasculaire cérébral/mortalité
14.
Circ Res ; 120(3): 559-572, 2017 Feb 03.
Article de Anglais | MEDLINE | ID: mdl-28154104

RÉSUMÉ

A complex interaction exists between the nervous and cardiovascular systems. A large network of cortical and subcortical brain regions control cardiovascular function via the sympathetic and parasympathetic outflow. A dysfunction in one system may lead to changes in the function of the other. The effects of cardiovascular disease on the nervous system have been widely studied; however, our understanding of the effects of neurological disorders on the cardiovascular system has only expanded in the past 2 decades. Various pathologies of the nervous system can lead to a wide range of alterations in function and structure of the cardiovascular system ranging from transient and benign electrographic changes to myocardial injury, cardiomyopathy, and even cardiac death. In this article, we first review the anatomy and physiology of the central and autonomic nervous systems in regard to control of the cardiovascular function. The effects of neurological injury on cardiac function and structure will be summarized, and finally, we review neurological disorders commonly associated with cardiovascular manifestations.


Sujet(s)
Encéphale/physiologie , Maladies cardiovasculaires/physiopathologie , Phénomènes physiologiques cardiovasculaires , Angiopathies intracrâniennes/physiopathologie , Maladies du système nerveux/physiopathologie , Encéphale/physiopathologie , Maladies cardiovasculaires/épidémiologie , Maladies cardiovasculaires/thérapie , Angiopathies intracrâniennes/épidémiologie , Angiopathies intracrâniennes/thérapie , Humains , Maladies du système nerveux/épidémiologie , Maladies du système nerveux/thérapie
16.
Neurol Clin Pract ; 6(1): 55-60, 2016 Feb.
Article de Anglais | MEDLINE | ID: mdl-26918203

RÉSUMÉ

PURPOSE OF REVIEW: Intravascular large B-cell lymphoma is a rare subtype of large B-cell lymphoma that affects various organs including the nervous system. The diagnosis is challenging and frequently made at autopsy. RECENT FINDINGS: We report 5 cases with an array of neurologic manifestations. All patients were initially evaluated for alternative diagnoses. Three patients were diagnosed at autopsy, one with brain biopsy, and another with muscle biopsy. Muscle was involved in all 3 patients who had muscle tissue available for analysis. SUMMARY: Our observations suggest that random open muscle biopsy may present a high-yield, less invasive option for the diagnosis of this disorder.

18.
Addict Biol ; 19(1): 49-60, 2014 Jan.
Article de Anglais | MEDLINE | ID: mdl-23017017

RÉSUMÉ

Modafinil may be useful for treating stimulant abuse, but the mechanisms by which it acts to do so are unknown. Indeed, a primary effect of modafinil is to inhibit dopamine transport, which typically promotes rather than inhibits motivated behavior. Therefore, we examined the role of nucleus accumbens extracellular glutamate and the group II metabotropic glutamate receptor (mGluR2/3) in modafinil effects. One group of rats was trained to self-administer cocaine for 10 days and extinguished, then given priming injections of cocaine to elicit reinstatement. Modafinil (300 mg/kg, intraperitoneal) inhibited reinstated cocaine seeking (but did not alter extinction responding by itself), and this effect was prevented by pre-treatment with bilateral microinjections of the mGluR2/3 antagonist LY-341495 (LY) into nucleus accumbens core. No reversal of modafinil effects was seen after unilateral accumbens core LY, or bilateral LY in the rostral pole of accumbens. Next, we sought to explore effects of modafinil on extracellular glutamate levels in accumbens after chronic cocaine. Separate rats were administered non-contingent cocaine, and after 3 weeks of withdrawal underwent accumbens microdialysis. Modafinil increased extracellular accumbens glutamate in chronic cocaine, but not chronic saline-pre-treated animals. This increase was prevented by reverse dialysis of cystine-glutamate exchange or voltage-dependent calcium channel antagonists. Voltage-dependent sodium channel blockade partly attenuated the increase in glutamate, but mGluR1 blockade did not. We conclude that modafinil increases extracellular glutamate in nucleus accumbens from glial and neuronal sources in cocaine-exposed rats, which may be important for its mGluR2/3-mediated antirelapse properties.


Sujet(s)
Composés benzhydryliques/pharmacologie , Troubles liés à la cocaïne/métabolisme , Comportement de recherche de substances/effets des médicaments et des substances chimiques , Glutamates/effets des médicaments et des substances chimiques , Noyau accumbens/effets des médicaments et des substances chimiques , Agents promoteurs de l'éveil/pharmacologie , Système y+ de transport d'acides aminés/antagonistes et inhibiteurs , Acides aminés/administration et posologie , Acides aminés/pharmacologie , Analyse de variance , Animaux , Composés benzhydryliques/administration et posologie , Cocaïne/administration et posologie , Modèles animaux de maladie humaine , Inhibiteurs de la capture de la dopamine/administration et posologie , Antagonistes des acides aminés excitateurs/administration et posologie , Antagonistes des acides aminés excitateurs/pharmacologie , Extinction (psychologie)/effets des médicaments et des substances chimiques , Glutamates/métabolisme , Mâle , Microdialyse/méthodes , Microinjections , Modafinil , Noyau accumbens/métabolisme , Rats , Rat Sprague-Dawley , Récepteurs métabotropes au glutamate/antagonistes et inhibiteurs , Récepteurs métabotropes au glutamate/métabolisme , Prévention secondaire , Autoadministration/statistiques et données numériques , Agents promoteurs de l'éveil/administration et posologie , Xanthènes/administration et posologie , Xanthènes/pharmacologie
19.
Behav Brain Res ; 237: 41-8, 2013 Jan 15.
Article de Anglais | MEDLINE | ID: mdl-22995645

RÉSUMÉ

Conditioned place preference (CPP) has been associated with orexinergic (hypocrtinergic) system activation in naïve mice; however, the distinct role of different receptors of orexin in this paradigm has not been characterized yet. Moreover, the relationship between orexins and morphine in dependent mice may not be equal to naïve mice and seems noteworthy to investigate. We investigated the effects of systemic administration of orexin-1-receptor antagonist, SB 334867, and orexin-2 receptor antagonist, TCS-OX2-29 on the acquisition and expression of morphine conditioned place preference (CPP) in both naïve and morphine-dependent mice. We tested SB 334867 in three doses (10, 20 and 30 mg/kg), TCS-OX2-29 in two doses (5 and 10 mg/kg) and morphine with highest effective dose based on our dose-response experiment (5 mg/kg). Our results revealed that while SB 334867 suppressed CPP acquisition and expression in naïve mice, it failed to block CPP acquisition and expression in morphine dependent animals. In contrast, TCS-OX2-29 suppressed CPP acquisition and expression in both naïve and dependent mice significantly. The rewarding effect of morphine has stronger correlation with orexin-2 receptors in morphine-dependent mice while it depends on both kinds of receptors in naïve mice. This finding, if confirmed in other studies, persuades us to further investigate the role of orexin-2 receptor antagonists as potent drugs in addiction treatment.


Sujet(s)
Analgésiques morphiniques/pharmacologie , Benzoxazoles/pharmacologie , Conditionnement opérant/effets des médicaments et des substances chimiques , Isoquinoléines/pharmacologie , Dépendance à la morphine/traitement médicamenteux , Morphine/pharmacologie , Pyridines/pharmacologie , Urée/analogues et dérivés , Analyse de variance , Animaux , Antigènes de surface/métabolisme , Modèles animaux de maladie humaine , Relation dose-effet des médicaments , Interactions médicamenteuses , Mâle , Souris , Dépendance à la morphine/physiopathologie , Naphtyridines , Récepteurs des orexines , Récepteurs de surface cellulaire/antagonistes et inhibiteurs , Récepteurs de surface cellulaire/métabolisme , Récepteur aux neuropeptides/antagonistes et inhibiteurs , Récepteur aux neuropeptides/métabolisme , Urée/pharmacologie
20.
Science ; 333(6040): 353-7, 2011 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-21764750

RÉSUMÉ

Reward-motivated behavior is strongly influenced by the learned significance of contextual stimuli in the environment. However, the neural pathways that mediate context-reward relations are not well understood. We have identified a circuit from area CA3 of dorsal hippocampus to ventral tegmental area (VTA) that uses lateral septum (LS) as a relay. Theta frequency stimulation of CA3 excited VTA dopamine (DA) neurons and inhibited non-DA neurons. DA neuron excitation was likely mediated by disinhibition because local antagonism of γ-aminobutyric acid receptors blocked responses to CA3 stimulation. Inactivating components of the CA3-LS-VTA pathway blocked evoked responses in VTA and also reinstatement of cocaine-seeking by contextual stimuli. This transsynaptic link between hippocampus and VTA appears to be an important substrate by which environmental context regulates goal-directed behavior.


Sujet(s)
Région CA3 de l'hippocampe/physiologie , Neurones/physiologie , Récompense , Noyaux du septum/physiologie , Aire tegmentale ventrale/physiologie , Potentiels d'action , Animaux , Comportement animal , Cartographie cérébrale , Cocaïne/administration et posologie , Dopamine/physiologie , Comportement de recherche de substances , Stimulation électrique , Agonistes GABA/pharmacologie , Antagonistes GABA/pharmacologie , Hippocampe/physiologie , Mâle , Modèles neurologiques , Inhibition nerveuse , Voies nerveuses , Rats , Rat Sprague-Dawley , Autoadministration , Rythme thêta , Acide gamma-amino-butyrique/administration et posologie , Acide gamma-amino-butyrique/physiologie
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