Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
JBJS Case Connect ; 13(4)2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38096338

RESUMO

CASE: A 50-year-old man presented with chronic refractory symptoms of radiating leg pain with muscle cramps because of a retained bullet in the calf after being shot in 1990. Radiographs confirmed the bullet lodged in posterolateral aspect of calf abutting proximal fibula. An intraoperative point-of-care ultrasound aided in accurate localization of bullet, thereby facilitating precise planning of surgical incision and subsequent removal. CONCLUSIONS: Ultrasound can be used as an alternative tool for safe surgical extraction of deep-seated metallic object with minimal tissue dissection, obviating the need for C-arm.


Assuntos
Corpos Estranhos , Perna (Membro) , Ultrassonografia , Ferimentos por Arma de Fogo , Humanos , Masculino , Pessoa de Meia-Idade , Fíbula , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Perna (Membro)/diagnóstico por imagem , Perna (Membro)/cirurgia , Dor/etiologia , Dor/cirurgia , Ferimentos por Arma de Fogo/cirurgia , Cuidados Intraoperatórios
2.
PeerJ Comput Sci ; 9: e1516, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37705656

RESUMO

PyMC is a probabilistic programming library for Python that provides tools for constructing and fitting Bayesian models. It offers an intuitive, readable syntax that is close to the natural syntax statisticians use to describe models. PyMC leverages the symbolic computation library PyTensor, allowing it to be compiled into a variety of computational backends, such as C, JAX, and Numba, which in turn offer access to different computational architectures including CPU, GPU, and TPU. Being a general modeling framework, PyMC supports a variety of models including generalized hierarchical linear regression and classification, time series, ordinary differential equations (ODEs), and non-parametric models such as Gaussian processes (GPs). We demonstrate PyMC's versatility and ease of use with examples spanning a range of common statistical models. Additionally, we discuss the positive role of PyMC in the development of the open-source ecosystem for probabilistic programming.

4.
Ochsner J ; 22(1): 80-84, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35355651

RESUMO

Background: Patellar instability is a common orthopedic condition in the pediatric population. Many factors contribute to patellar instability, including trochlear dysplasia. However, patellar instability and its treatments are not well documented in the literature for patients with osteogenesis imperfecta. Case Report: After medial patellofemoral ligament (MPFL) reconstruction, a 17-year-old male with osteogenesis imperfecta had a patellar dislocation that resulted in a patellar fracture. The patient subsequently had a revision of his MPFL reconstruction, and at 2½ years postoperation has had no episodes of recurrent patellar instability. Conclusion: The combination of bone fragility, trochlear dysplasia, and strength of the allograft used for MPFL reconstruction compared to the patient's bone strength led to dislocation and patellar fracture. Research into alternative methods for patellar fixation and postoperative physical therapy protocols for patients with osteogenesis imperfecta is needed. Special considerations must be made for this patient population.

5.
Hand (N Y) ; 17(4): NP7-NP11, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34963324

RESUMO

Catfish have the ability to inflict stings on their victims through spines located on their dorsal and pectoral fins. The stings of catfish can release toxins that have dermonecrotic, edemogenic, and vasospastic factors. In this case, a 56-year-old man suffered a catfish sting to his right thumb, which resulted in acute hand compartment syndrome and resultant hand fasciotomies. His hospital course was complicated by multiple irrigation and debridements, finger amputations, hand fluid cultures positive for Vibrio damsela, and eventual wrist disarticulation. The combination of envenomation, infection, and delayed presentation for treatment ultimately led to a hand amputation.


Assuntos
Mordeduras e Picadas , Peixes-Gato , Síndromes Compartimentais , Animais , Mordeduras e Picadas/complicações , Mordeduras e Picadas/cirurgia , Síndromes Compartimentais/etiologia , Desarticulação/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Punho
6.
Ochsner J ; 20(3): 339-342, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33071673

RESUMO

Background: Hip fracture is a common orthopedic condition that leads to many hospitalizations each year. Intertrochanteric femur fractures are commonly treated with cephalomedullary nail fixation. Superior gluteal artery bleed is a rare complication of cephalomedullary nail fixation, especially when the trochanteric approach is used. Case Report: A 63-year-old male presented to the emergency department with a right intertrochanteric femur fracture after a fall from standing height. Cephalomedullary nail fixation was performed without any complications during the operation. The patient's postoperative course was complicated by decreasing hemoglobin levels despite blood transfusions. Superior gluteal artery bleed with a large hematoma was discovered on postoperative day 4. The bleed was embolized, and the patient was stabilized and discharged. Conclusion: We found only 1 published report of a superior gluteal artery bleed associated with nail placement. During the operative procedure, guidewire placement requires careful consideration because of the risk of vascular damage. Superior gluteal artery injury, although rare, should be considered in patients with unstable hemoglobin levels after nail placement.

7.
Am Surg ; 84(11): 1750-1755, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30747628

RESUMO

Tension pneumothorax is commonly treated with needle decompression (ND) at the 2nd intercostal space midclavicular line (2nd ICS MCL) but is thought to have a high failure rate. Few studies have attempted to directly measure the failure rate in patients receiving the intervention. We performed a retrospective analysis of 10 years of patients receiving prehospital ND. CT scans were reviewed to record the location of catheters left indwelling and the proportion of patients who did not have any pneumothorax. Chest wall thickness was measured on both injured and uninjured sides at the 2nd ICS MCL and compared with the recommended alternative, the 5th ICS anterior axillary line (5th ICS AAL). We identified 335 patients that underwent prehospital ND who had CT scans performed. Using our two different radiologic methods of assessing failure, 39 per cent and 76 per cent of attempts at ND failed to reach the pleural space. In addition, at least 39 per cent of patients did not have a tension pneumothorax. Injured chest walls were significantly thicker than uninjured chest walls at both the 2nd ICS MCL and the 5th ICS AAL (both P < 0.005.) Increasing chest wall thickness correlated with the failure of the catheter to reach the pleural space. Using an 8-cm catheter at the 5th ICS AAL, iatrogenic cardiac injury was at risk in 42 per cent of patients. This series confirms the high failure rate of ND at the 2nd ICS MCL, but further studies are needed to assure the safety of using larger catheters at the 5th ICS AAL.


Assuntos
Descompressão Cirúrgica/instrumentação , Serviços Médicos de Emergência/métodos , Agulhas , Pneumotórax/cirurgia , Centros Médicos Acadêmicos , Adulto , Cateterismo/instrumentação , Estudos de Coortes , Descompressão Cirúrgica/efeitos adversos , Descompressão Cirúrgica/métodos , Emergências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumotórax/diagnóstico por imagem , Estudos Retrospectivos , Medição de Risco , Tennessee , Tomografia Computadorizada por Raios X/métodos , Centros de Traumatologia , Falha de Tratamento
8.
Orthopedics ; 36(8): e1065-70, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23937755

RESUMO

The purpose of this study was to determine the incidence of and evaluate the risk for complications and mortality following open treatment of acetabular fractures in the Medicare population. Patients treated with open reduction and internal fixation (ORIF) for acetabular fractures were identified using current procedural terminology codes in a 5% national sample of Medicare records. Complications within 90 days and within 1 year were evaluated based on the presence of ICD-9-CM diagnosis codes and Current Procedural Terminology reoperation codes. A total of 1286 fractures were treated closed and 359 were treated with ORIF. Multivariate Cox regression was performed to compare complication rates and risk factors. The incidence of acetabular fractures in the Medicare population has increased by 29% since 1998. Complications in the ORIF group included cardiac complications, deep venous thrombosis, infection, pulmonary embolism, refixation, and conversion to total hip arthroplasty. Risk factors for complications with ORIF included advanced age and comorbidities. Mortality in the ORIF group was 14.4% at 1 year. The incidence of reoperation with conversion to total hip arthroplasty or revision fixation following ORIF is 10% and 15%, respectively. Further investigation is required to improve outcomes and decrease complications in this group of patients, especially cardiac, deep vein thrombosis, and infection.


Assuntos
Acetábulo/lesões , Fixação Interna de Fraturas/mortalidade , Fraturas Ósseas/mortalidade , Fraturas Ósseas/cirurgia , Medicare/estatística & dados numéricos , Osteotomia/mortalidade , Complicações Pós-Operatórias/mortalidade , Idoso , Idoso de 80 Anos ou mais , Animais , Gatos , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia
9.
Arch Gen Psychiatry ; 69(1): 27-36, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22213786

RESUMO

CONTEXT: The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing. OBJECTIVE: To examine the effects of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) on regional brain function during salience processing. DESIGN: Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of Δ9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli. SETTING: University center. PARTICIPANTS: Fifteen healthy men with minimal previous cannabis use. MAIN OUTCOME MEASURES: Symptom ratings, task performance, and regional brain activation. RESULTS: During the processing of oddball stimuli, relative to placebo, Δ9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. Δ9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of Δ9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of Δ9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation. CONCLUSIONS: Δ9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders.


Assuntos
Atenção/efeitos dos fármacos , Canabidiol/efeitos adversos , Corpo Estriado/efeitos dos fármacos , Dronabinol/efeitos adversos , Alucinógenos/efeitos adversos , Córtex Pré-Frontal/efeitos dos fármacos , Transtornos Psicóticos/fisiopatologia , Adulto , Atenção/fisiologia , Corpo Estriado/fisiopatologia , Humanos , Masculino , Córtex Pré-Frontal/fisiopatologia , Transtornos Psicóticos/psicologia , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Percepção Espacial/efeitos dos fármacos , Percepção Espacial/fisiologia , Adulto Jovem
10.
Am Surg ; 77(4): 476-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21679559

RESUMO

Trauma centers are limited resources, particularly in rural areas, and availability of emergency care in some parts of the United States may be inadequate. The declining number of orthopedic surgeons willing to care for injured patients has limited access to fracture repair in some communities. We studied the management of closed midshaft femur fractures in both trauma centers (TCs) and nontrauma centers (NTCs) to evaluate outcome for this common orthopedic injury and determine if these issues have affected fracture care in Kentucky. All patients 16-years-old and older who suffered femur fractures in Kentucky from 2004 and 2005 were identified. There were 334 TC patients and 341 NTC patients with closed, midshaft femur fractures. The mean age of TC patients (33 ± 17 years) was significantly lower than that of NTC patients (59 ± 25 years). TC patients were more likely men (71% vs 44%), had more associated injuries (2.4 ± 2.1 vs 0.5 ± 1.2), and had longer lengths of stay (8.3 ± 9.8 vs 6.4 ± 7.1 days) (TCs vs NTCs, all P < 0.005). Although both groups ultimately underwent internal fixation (97% vs 99%, TCs vs NTCs), TC patients were more likely (2.7% vs 0.3%) to receive external fixation than the NTC patients (P < 0.05). There was no significant difference in the percentage of patients that received only a closed reduction. There was no significant difference in hospital mortality (0.3% vs 0.9%, TCs vs NTCs, P = 0.62). Although differences in patient populations exist between TCs and NTCs, both TCs and NTCs manage substantial numbers of patients with closed, midshaft femur fractures with low mortality in this state database.


Assuntos
Fraturas do Fêmur/terapia , Fixação de Fratura , Fraturas Fechadas/terapia , Avaliação de Resultados em Cuidados de Saúde , Adulto , Comorbidade , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Fraturas do Fêmur/economia , Fraturas do Fêmur/epidemiologia , Fixação de Fratura/economia , Fixação de Fratura/métodos , Fraturas Fechadas/economia , Fraturas Fechadas/epidemiologia , Preços Hospitalares , Mortalidade Hospitalar , Humanos , Kentucky/epidemiologia , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/epidemiologia , Centros de Traumatologia/estatística & dados numéricos
11.
Nature ; 472(7344): 466-70, 2011 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-21460835

RESUMO

Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus throughout life. Neurons that arise in adults (adult-born neurons) show heightened synaptic plasticity during their maturation and can account for up to ten per cent of the entire granule cell population. Moreover, levels of adult hippocampal neurogenesis are increased by interventions that are associated with beneficial effects on cognition and mood, such as learning, environmental enrichment, exercise and chronic treatment with antidepressants. Together, these properties of adult neurogenesis indicate that this process could be harnessed to improve hippocampal functions. However, despite a substantial number of studies demonstrating that adult-born neurons are necessary for mediating specific cognitive functions, as well as some of the behavioural effects of antidepressants, it is unknown whether an increase in adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished. Mice with increased adult hippocampal neurogenesis show normal object recognition, spatial learning, contextual fear conditioning and extinction learning but are more efficient in differentiating between overlapping contextual representations, which is indicative of enhanced pattern separation. Furthermore, stimulation of adult hippocampal neurogenesis, when combined with an intervention such as voluntary exercise, produces a robust increase in exploratory behaviour. However, increasing adult hippocampal neurogenesis alone does not produce a behavioural response like that induced by anxiolytic agents or antidepressants. Together, our findings suggest that strategies that are designed to increase adult hippocampal neurogenesis specifically, by targeting the cell death of adult-born neurons or by other mechanisms, may have therapeutic potential for reversing impairments in pattern separation and dentate gyrus dysfunction such as those seen during normal ageing.


Assuntos
Afeto/fisiologia , Envelhecimento/fisiologia , Cognição/fisiologia , Hipocampo/citologia , Hipocampo/fisiologia , Modelos Neurológicos , Neurogênese/fisiologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Animais , Antidepressivos/farmacologia , Ansiedade/fisiopatologia , Ansiedade/terapia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Giro Denteado/citologia , Giro Denteado/patologia , Giro Denteado/fisiologia , Giro Denteado/fisiopatologia , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Extinção Psicológica/efeitos dos fármacos , Extinção Psicológica/fisiologia , Medo/fisiologia , Medo/psicologia , Feminino , Hipocampo/patologia , Hipocampo/fisiopatologia , Aprendizagem/efeitos dos fármacos , Aprendizagem/fisiologia , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Neurogênese/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Condicionamento Físico Animal/fisiologia , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Proteína X Associada a bcl-2/deficiência , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
12.
Neuropsychopharmacology ; 35(3): 764-74, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19924114

RESUMO

Delta-9-tetrahydrocannabinol (Delta-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Delta-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Delta-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of Delta-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Delta-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Delta-9-THC. Delta-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task, in the amygdala when subjects viewed fearful faces, in the superior temporal cortex when subjects listened to speech, and in the occipital cortex during visual processing. In the second experiment, pretreatment with CBD prevented the acute induction of psychotic symptoms by Delta-9-tetrahydrocannabinol. Delta-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of Delta-9-THC.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Canabidiol/farmacologia , Dronabinol/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Estimulação Acústica/métodos , Adulto , Método Duplo-Cego , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos Mentais/patologia , Transtornos Mentais/fisiopatologia , Transtornos Mentais/prevenção & controle , Estimulação Luminosa/métodos , Desempenho Psicomotor/fisiologia , Adulto Jovem
13.
Arch Gen Psychiatry ; 66(4): 442-51, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19349314

RESUMO

CONTEXT: Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms. OBJECTIVES: To investigate the effects of 2 main psychoactive constituents of C. sativa, Delta9-tetrahydrocannabinol (Delta9-THC) and cannabidiol, on regional brain function during verbal paired associate learning. DESIGN: Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design. SETTING: University research center. PARTICIPANTS: Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime. MAIN OUTCOME MEASURES: Regional brain activation (blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation. RESULTS: Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect. CONCLUSION: The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms, respectively.


Assuntos
Cannabis , Corpo Estriado/efeitos dos fármacos , Dronabinol/farmacologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Oxigênio/sangue , Aprendizagem por Associação de Pares/efeitos dos fármacos , Psicoses Induzidas por Substâncias/fisiopatologia , Lobo Temporal/efeitos dos fármacos , Administração Oral , Adulto , Nível de Alerta/efeitos dos fármacos , Atenção/efeitos dos fármacos , Canabidiol/farmacocinética , Canabidiol/farmacologia , Método Duplo-Cego , Dronabinol/farmacocinética , Humanos , Masculino , Rememoração Mental/efeitos dos fármacos , Giro Para-Hipocampal/efeitos dos fármacos
14.
Biol Psychiatry ; 64(11): 966-73, 2008 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-18589404

RESUMO

BACKGROUND: This study examined the effect of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on brain activation during a motor inhibition task. METHODS: Functional magnetic resonance imaging and behavioural measures were recorded while 15 healthy volunteers performed a Go/No-Go task following administration of either THC or CBD or placebo in a double-blind, pseudo-randomized, placebo-controlled repeated measures within-subject design. RESULTS: Relative to placebo, THC attenuated activation in the right inferior frontal and the anterior cingulate gyrus. In contrast, CBD deactivated the left temporal cortex and insula. These effects were not related to changes in anxiety, intoxication, sedation, and psychotic symptoms. CONCLUSIONS: These data suggest that THC attenuates the engagement of brain regions that mediate response inhibition. CBD modulated function in regions not usually implicated in response inhibition.


Assuntos
Mapeamento Encefálico , Encéfalo/efeitos dos fármacos , Canabidiol/farmacologia , Dronabinol/farmacologia , Inibição Psicológica , Psicotrópicos/farmacologia , Adulto , Análise de Variância , Encéfalo/anatomia & histologia , Encéfalo/irrigação sanguínea , Tomada de Decisões/efeitos dos fármacos , Tomada de Decisões/fisiologia , Método Duplo-Cego , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Testes Neuropsicológicos , Oxigênio/sangue , Estimulação Luminosa , Tempo de Reação/efeitos dos fármacos , Adulto Jovem
15.
Learn Mem ; 13(6): 760-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17142305

RESUMO

The persistence of new memory traces in the hippocampus, encoded following appropriate activation of glutamatergic receptors and the induction of synaptic plasticity, can be influenced by heterosynaptic activation of neuromodulatory brain systems. We therefore investigated the effects of a hippocampus-specific blockade of dopamine D1/D5 receptors on the persistence of spatial memory encoded in one trial using a delayed matching-to-place (DMP) task in a watermaze in which rats learn a new escape location each day. A within-subjects design was used such that both short (20 min) and long (6 h) retention intervals, and both drug (SCH23390, a D1/D5 receptor antagonist) and vehicle (aCSF) infusions were tested on different days in the same animals. Bilateral intrahippocampal infusion of SCH23390 (5 microg in 1 microL per side) prior to trial 1 (encoding) caused a differential impairment as a function of memory delay-with no effect during trial 2 (memory retrieval) after a 20-min interval, but a block of memory at 6 h. Further experiments revealed that infusion of SCH23390 immediately after trial 1 had no effect on retention 6 h later, and the poor memory seen at long retention intervals when the drug was present at encoding was not due to a state-dependent failure of retrieval. These results suggest that activation of D1/D5 receptors during memory encoding is necessary for the formation of a persistent memory trace in the hippocampus. The complementary effects of D1/D5 receptor blockade on the persistence of LTP and the duration of memory are consistent with the idea that changes in synaptic strength underlie memory.


Assuntos
Dopamina/metabolismo , Hipocampo/metabolismo , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Análise de Variância , Animais , Dopaminérgicos/farmacologia , Reação de Fuga/efeitos dos fármacos , Reação de Fuga/fisiologia , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Receptores de Dopamina D1/efeitos dos fármacos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D5/efeitos dos fármacos , Receptores de Dopamina D5/metabolismo , Comportamento Espacial/efeitos dos fármacos , Comportamento Espacial/fisiologia , Estatísticas não Paramétricas
16.
Neuropharmacology ; 47(3): 324-32, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15275821

RESUMO

The persistence of protein synthesis-dependent long-term potentiation (late-LTP) is thought to require heterosynaptic activation of both glutamate and neuromodulatory receptors in the hippocampus. The present series of experiments contrasts two alternative accounts of heterosynaptic activation. The original version of the synaptic-tag hypothesis of the variable persistence of LTP implied that neuromodulatory and glutamatergic activation could occur independently, albeit within a critical time-window; an alternative view is that there needs to be simultaneous co-activation of both receptors to trigger the up-regulation of relevant protein synthesis (Neuron 34 (2002) 235). Our findings include a replication, over 6 h post-LTP-induction, of earlier findings showing heterosynaptic influences on LTP persistence. Specifically, 'strong' tetanisation with multiple trains of stimulation of one input pathway in a conventional hippocampal slice preparation induces a D1/D5 receptor-dependent form of late-LTP that enables 'weak' tetanic stimulation to induce late-LTP on an independent pathway. However, we also observed that when the first pathway was tetanised in the presence of AP5, not only was no LTP observed on that pathway, but there was also no rescue of late-LTP on the second pathway. Thus, it appears that DA receptors must be co-activated with NMDA receptors in a common pool of neurons to enable LTP persistence, although late-LTP can still be induced by selective activation of glutamatergic synapses if this occurs at time periods shortly before or shortly after this essential coactivation.


Assuntos
Dopamina/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/citologia , Potenciação de Longa Duração/fisiologia , Neurônios Aferentes/fisiologia , Sinapses/fisiologia , Valina/análogos & derivados , Animais , Benzazepinas/farmacologia , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta à Radiação , Estimulação Elétrica/métodos , Agonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Hipocampo/efeitos dos fármacos , Hipocampo/efeitos da radiação , Técnicas In Vitro , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/efeitos da radiação , Masculino , Neurônios Aferentes/efeitos da radiação , Ratos , Ratos Wistar , Sinapses/efeitos dos fármacos , Sinapses/efeitos da radiação , Fatores de Tempo , Valina/farmacologia
17.
J Neurosci ; 22(22): 9721-32, 2002 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-12427827

RESUMO

At excitatory synapses, the postsynaptic scaffolding protein postsynaptic density 95 (PSD-95) couples NMDA receptors (NMDARs) to the Ras GTPase-activating protein SynGAP. The close association of SynGAP and NMDARs suggests that SynGAP may have an important role in NMDAR-dependent activation of Ras signaling pathways, such as the MAP kinase pathway, and in synaptic plasticity. To explore this issue, we examined long-term potentiation (LTP), p42 MAPK (ERK2) signaling, and spatial learning in mice with a heterozygous null mutation of the SynGAP gene (SynGAP(-/+)). In SynGAP(-/+) mutant mice, the induction of LTP in the hippocampal CA1 region was strongly reduced in the absence of any detectable alteration in basal synaptic transmission and NMDAR-mediated synaptic currents. Although basal levels of activated ERK2 were elevated in hippocampal extracts from SynGAP(-/+) mice, NMDAR stimulation still induced a robust increase in ERK activation in slices from SynGAP(-/+) mice. Thus, although SynGAP may regulate the ERK pathway, its role in LTP most likely involves additional downstream targets. Consistent with this, the amount of potentiation induced by stimulation protocols that induce an ERK-independent form of LTP were also significantly reduced in slices from SynGAP(-/+) mice. An elevation of basal phospho-ERK2 levels and LTP deficits were also observed in SynGAP(-/+)/H-Ras(-)/- double mutants, suggesting that SynGAP may normally regulate Ras isoforms other than H-Ras. A comparison of SynGAP and PSD-95 mutants suggests that PSD-95 couples NMDARs to multiple downstream signaling pathways with very different roles in LTP and learning.


Assuntos
Proteínas Ativadoras de GTPase/metabolismo , Aprendizagem/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Plasticidade Neuronal/fisiologia , Sinapses/metabolismo , Animais , Proteína 4 Homóloga a Disks-Large , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/fisiologia , Viabilidade Fetal/genética , Proteínas Ativadoras de GTPase/genética , Marcação de Genes , Guanilato Quinases , Heterozigoto , Hipocampo/química , Hipocampo/citologia , Hipocampo/metabolismo , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intracelular , Potenciação de Longa Duração/fisiologia , Substâncias Macromoleculares , Proteínas de Membrana , Camundongos , Camundongos Mutantes , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Técnicas de Patch-Clamp , Receptores de N-Metil-D-Aspartato/metabolismo , Transmissão Sináptica/fisiologia , Proteínas ras/genética , Proteínas ras/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...