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1.
World Neurosurg ; 136: 357-363.e2, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32001414

RESUMO

BACKGROUND: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a recently approved therapy for patients with drug-resistant epilepsy. To date, there is a poor understanding of the mechanism of action and lack of in vivo biomarkers. We propose a method for investigating the in vivo stimulation effects using blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI) and present the brain activation pattern associated with ANT DBS. METHODS: Two patients undergoing ANT DBS for epilepsy underwent BOLD MRI using a block design after the DBS was programmed to alternate ON/OFF in 30-second blocks. The scanner was triggered using surface electrophysiologic recordings to detect the DBS cycle. Nine total runs were obtained and were analyzed using a general linear model. RESULTS: Active ANT stimulation produced activation within several areas of the brain, including the thalamus, bilateral anterior cingulate and posterior cingulate cortex, precuneus, medial prefrontal cortex, amygdala, ventral tegmental area, hippocampus, striatum, and right angular gyrus. CONCLUSIONS: Using block-design BOLD MRI, we were able to show widespread activation resulting from ANT DBS. Overlap with multiple areas of both the default mode and limbic networks was shown, suggesting that these nodes may modulate the effect of seizure control with ANT DBS.

2.
Brain Behav ; 9(7): e01336, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31140760

RESUMO

INTRODUCTION: Patients under chronic obstructive pulmonary disease (COPD) has been reported to be associated with a higher prevalence of cognitive impairment (CI). However, it is still largely unknown whether the aberrant resting-state spontaneous neuronal activity pattern reflected by the amplitude of low-frequency fluctuation (ALFF) analysis will be associated with the CI in COPD patients. MATERIALS: A total of 28 COPD patients and 26 healthy controls were enrolled in this study. Of all the subjects, structural and functional MRI data, spirometry tests performance and neuropsychological assessments of different cognitive domains were collected. Voxel-based two-sample t tests were used to detect brain regions showing differences in the ALFF value between COPD patients and healthy controls. An additional fMRI runs with supplementary oxygen delivery were employed to explore the impact of elevated partial pressure of oxygen (PaO2 ) or moderate hyperoxia on ALFF in COPD patients and healthy controls respectively. RESULTS: More extensive white matter lesion was detected in COPD patients. COPD patients exhibit decreased ALFF value in bilateral basal ganglia areas and right thalamus, and aberrant ALFF value is correlated with PaO2 and pulmonary ventilation function (FEV1%pred). COPD patients performed worse in the Digit Span Test (reverse), Digit Symbol Substitution Test, Trail-making test (A and B) than controls. After supplementary oxygen inhalation, the ALFF value of basal ganglia and right thalamus significantly increased in the controls, but not in the COPD patients. CONCLUSIONS: COPD patients mainly exhibit impaired executive function but not long-term memory in cognitive function assessment. Aberrant ALFF alteration in the deep brain may be directly related to lower PaO2 in COPD patients.

3.
Neural Plast ; 2019: 8354849, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049056

RESUMO

Abnormal neural activity in the cerebellum has been implicated in hearing impairments, but the effects of long-term hearing loss on cerebellar function are poorly understood. To further explore the role of long-term bilateral sensorineural hearing loss on cerebellar function, we investigated hearing loss-induced changes among neural networks within cerebellar subregions and the changes in cerebellar-cerebral connectivity patterns using resting-state functional MRI. Twenty-one subjects with long-term bilateral moderate-to-severe sensorineural hearing loss and 21 matched controls with clinically normal hearing underwent MRI scanning and a series of neuropsychological tests targeting cognition and emotion. Voxel-wise functional connectivity (FC) analysis demonstrated decreased couplings between the cerebellum and other cerebral areas, including the temporal pole (TP), insula, supramarginal gyrus, inferior frontal gyrus (IFG), medial frontal gyrus, and thalamus, in long-term bilateral sensorineural hearing loss patients. An ROI-wise FC analysis found weakened interregional connections within cerebellar subdivisions. Moreover, there was a negative correlation between anxiety and FC between the left cerebellar lobe VI and left insula. Hearing ability and anxiety scores were also correlated with FC between the left cerebellar lobe VI and left TP, as well as the right cerebellar lobule VI and left IFG. Our results suggest that sensorineural hearing loss disrupts cerebellar-cerebral circuits, some potentially linked to anxiety, and interregional cerebellar connectivity. The findings contribute to a growing body showing that auditory deprivation caused by cochlear hearing loss disrupts not only activity with the classical auditory pathway but also portions of the cerebellum that communicates with other cortical networks.


Assuntos
Percepção Auditiva/fisiologia , Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Perda Auditiva Neurossensorial/fisiopatologia , Estimulação Acústica , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Limiar Sensorial
4.
Front Neurosci ; 13: 246, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941010

RESUMO

Sensorineural hearing loss (SNHL), sometimes accompanied with tinnitus, is associated with dysfunctions within and outside the classical auditory pathway. The salience network, which is anchored in bilateral anterior insula and dorsal anterior cingulate cortex, has been implicated in sensory integration. Partial auditory deprivation could alter the characteristics of the salience network and other related brain areas, thereby contributing to hearing impairments-induced neuropsychiatric symptoms. To test this hypothesis, we performed fMRI scanning and neuropsychological tests on 32 subjects with long-term bilateral hearing impairment and 30 well-matched Controls. Non-directional functional connectivity and directional Granger causality analysis were used to identify aberrant spatial and temporal patterns of connections targeting bilateral anterior insula and dorsal anterior cingulate cortex. We found that the left anterior insula showed decreased connectivity with right precentral gyrus and superior frontal gyrus. The connections between the dorsal anterior cingulate cortex and middle frontal gyrus, superior parietal gyrus and supplementary motor area (SMA) were also reduced. Relative to Controls, SNHL patients showed abnormal effective connectivity of the salience network, including inferior temporal gyrus, cerebellum lobule VI, lobule VIII, precentral gyrus, middle frontal gyrus and SMA. Furthermore, correlation analysis demonstrated that some of these atypical connectivity measures were correlated with performance of neuropsychiatric tests. These findings suggest that the inefficient modulation of the salience network might contribute to the neural basis of SNHL and tinnitus, as well as associated cognition and emotion deficits.

5.
J Magn Reson Imaging ; 50(3): 787-797, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30694013

RESUMO

BACKGROUND: The thalamus is an integrative hub conveying sensory information between cortical areas and related to cognition. However, alterations of the thalamus following partial hearing deprivation remains unknown. PURPOSE: To investigate the modifications of the thalamus and its seven subdivisions in terms of structure, function, and perfusion in subjects with sensorineural hearing loss (SNHL), as well as their associations with SNHL-induced cognitive impairments. STUDY TYPE: Cross-sectional study. SUBJECTS: Thirty-seven bilateral long-term SNHL patients and 38 well-matched controls. FIELD STRENGTH: 3 T/BOLD, T1 -weighted imaging, arterial spin labeling (ASL). ASSESSMENT: Quantitative measurements in the thalamus and subdivisions were obtained, including the relative volume, fractional amplitude of low-frequency fluctuation (fALFF) within slow 5 (0.01-0.027 Hz), slow 4 (0.027-0.073 Hz), and combined frequency (0.01-0.073 Hz), as well as the whole-brain functional connectivity. Twenty-five SNHL patients and 20 controls underwent ASL scanning. Then correlation analysis was computed between all significant changes and cognition tests. STATISTICAL TESTS: Continuous and categorical variables were compared by independent-sample t-test and chi-square test, respectively. Quantitative MRI measurement comparisons were corrected for multiple comparison, and functional connectivity (FC) analysis used two-sample t-test with false-discovery rate correction. Area under the curve (AUC) in receiver operating characteristic curve analysis was applied to evaluate the power of alterations in differentiating SNHL and controls. RESULTS: No significant difference in the relative volume and perfusion of seven thalamus subdivisions were observed, but a decrease in fALFF in SNHL. SNHL showed reduced thalamic connectivity with the cerebellum lobule VIII, ventral anterior cingulate cortex, insula, superior temporal gyrus, media temporal gyrus, medial frontal gyrus, Heschl's gyrus, and temporal pole. And some FC abnormalities exhibited positive correlations with cognitive tests and high discriminative power (0.8 < AUC < 1) in two groups. DATA CONCLUSION: SNHL led to decreased thalamic activity and widespread weakened connectivity with other brain areas. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:787-797.

6.
Eur Radiol ; 29(5): 2233-2242, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30523453

RESUMO

OBJECTIVES: To identify CT markers for screening of early type 2 diabetes and assessment of the risk of incident diabetes using a radiomics method. METHODS: The medical records of 26,947 inpatients were reviewed. A total of 690 patients were selected and allocated to a primary cohort, a validation cohort, and a prediction cohort and used to build prediction models for diabetes. Three radiomics signatures were constructed using CT image features extracted from three regions of interest, i.e., in the pancreas, liver, and psoas major muscle. By incorporating radiomics signatures and other markers, we built a radiomics nomogram that could be used to screen for early diabetes and predict future diabetes. RESULTS: Of the three abdominal organs for which radiomics signature were constructed, that of the pancreas showed the best discriminatory power for early diabetes screening and prediction (C-statistics of 0.833, 0.846, and 0.899 for the primary cohort, validation cohort, and prediction cohort, respectively). The sensitivity and specificity of the nomogram for prediction of 3-year incident diabetes were 0.827 and 0.807, respectively. CONCLUSIONS: This study presents alternative radiomics markers that have potential for use in screening for undiagnosed type 2 diabetes and prediction of 3-year incident diabetes. KEY POINTS: • CT images may provide useful information to evaluate the risk of developing diabetes. • Radiomics score for diabetes prediction is based on subtle changes of abdominal organs detected by CT. • The radiomics signature of pancreas, a combination of five features of CT images, is efficient for early diabetes screening and prediction of future diabetes (AUC > 0.8).


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Tomografia Computadorizada Multidetectores/métodos , Nomogramas , Radiografia Abdominal/métodos , Medição de Risco/métodos , Tecido Adiposo/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
7.
Neuroimage Clin ; 20: 800-807, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30268989

RESUMO

Aberrant brain structural change in cirrhotic patients with or without hepatic encephalopathy is one of the most typical cases in voxel-based morphometry (VBM) studies. However, there exist inconsistent results regarding to the volume change of the thalamus. Furthermore, the relationship between thalamus structural change and cirrhotic symptoms has not yet been fully elucidated. To address these two issues, we repeated two VBM analyses in SPM and FreeSurfer and compared the two measurements with manually measured thalamic volumes. We also correlated the VBM results with clinical indexes related to cirrhosis to further investigate the relationship between thalamic structural change and liver cirrhosis. The inconsistent result of thalamic structural change was successfully reproduced in regard to the volume measurements of SPM and FreeSurfer. The manually measured results demonstrate an increase in the volume of the thalamus in cirrhotic patients compared to healthy controls, which differs from the results of FreeSurfer. The structural change of thalamus closely correlated with the blood biochemical indexes, including albumin levels, blood coagulation time, and AST/ALT ratio. All of these biochemical indexes are closely related to the severity of liver cirrhosis. Beyond all the results, this study also provides a good demonstration of the difference between multiple VBM measurements for clinicians.


Assuntos
Encefalopatia Hepática/patologia , Cirrose Hepática/complicações , Tálamo/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Encefalopatia Hepática/complicações , Encefalopatia Hepática/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Tálamo/diagnóstico por imagem
8.
Quant Imaging Med Surg ; 8(6): 579-587, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30140620

RESUMO

Background: Obesity is considered a challenging public problem, which has been proven to be closely associated with coronary artery disease (CAD). Each risk factor of CAD has been separately studied many times in the past, but very few have comprehensively and quantitatively evaluated the relationship between the abdominal fat-related parameters and severity of CAD. The aim of this study was to analyze whether the abdominal fat-related parameters were associated with severity of CAD using abdominal non-enhanced computed tomography (NECT). Methods: Patients who went through both abdominal NECT and invasive coronary angiography (ICA) were included and retrospectively analyzed. The abdominal fat-related parameters [the ratio of visceral adipose tissue to subcutaneous adipose tissue (VAT/SAT ratio)] and traditional cardiovascular risk factors were evaluated in the participants with or without obstructive CAD. The correlations between the abdominal fat-related parameters and severity of CAD were assessed, and the multivariable logistic regression analysis was performed to investigate the parameters that could be used to predict the severity of CAD. Results: A total of 223 consecutive subjects (obstructive CAD group, n=117; non-obstructive CAD group, n=106) were analyzed. The VAT/SAT ratio was significantly higher (0.95±0.33 vs. 0.70±0.25, P<0.001) in obstructive CAD (O-CAD) patients than that in non-obstructive CAD (NO-CAD) patients. There was a trend to having nonalcoholic fatty liver disease (NAFLD) in the O-CAD patients than that of NO-CAD (P=0.002); the abdominal aortic calcification (AAC) score in O-CAD patients were higher than that in NO-CAD patients (P<0.001). The multivariable logistic regression analysis demonstrated that VAT/SAT ratio, NAFLD, and AAC score were independent predictors of O-CAD after adjusting the traditional cardiovascular risk factors. The area under the curve (AUC) of the combination of the above risk factors is 0.85, which leads to an increase in AUC than each risk factor alone in differentiating patients with or without O-CAD. Conclusions: VAT/SAT ratio, NAFLD, and AAC score are correlated with the severity of CAD, indicating their characteristics of being independent risk factors for O-CAD, irrespective of the traditional cardiovascular risk factors. Those CT-derived parameters may make positive contributions to the differentiation of the patients with increased risk of O-CAD.

9.
Eur Radiol ; 28(8): 3326-3334, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29450711

RESUMO

OBJECTIVE: To investigate the renal fat fraction and water molecular diffusion features in patients with early-stage DN using Dixon imaging and diffusion tensor imaging (DTI). METHODS: Sixty-one type 2 diabetics (normoalbuminuria: n = 40; microalbuminuria: n = 21) and 34 non-diabetic volunteers were included. All participants received three-point Dixon imaging and DTI using a 3.0-T magnetic resonance imager. The fat fraction [FF] and DTI features [fractional anisotropy (FA), apparent diffusion coefficient (ADC), tract counts and length from DTI tractography] were collected. All image features were compared between cohorts using one-way ANOVA with Bonferroni post-hoc analysis. RESULTS: Renal FF in the microalbuminuric group was significantly higher than in the normoalbuminuric and control groups (5.6% ± 1.3%, 4.7% ± 1.1% and 4.3% ± 0.5%, respectively; p < 0.001). Medullary FA in the microalbuminuric group was the lowest (0.31 ± 0.06) in all cohorts. The tract counts and length in the renal medulla were significantly lower in the microalbuminuric group than in the other two groups. CONCLUSIONS: Dixon imaging and DTI are able to detect renal lipid deposition and water molecule diffusion abnormalities in patients with early-stage DN. Both techniques have the potential to noninvasively evaluate early renal impairment in type 2 diabetes. KEY POINTS: • Dixon imaging demonstrated renal fat deposition in early-stage DN; • Renal fractional anisotropy decreased in patients with early-stage DN; • Renal tractography demonstrated reduced track counts and length in early-stage DN.


Assuntos
Tecido Adiposo/patologia , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/patologia , Insuficiência Renal/patologia , Idoso , Análise de Variância , Anisotropia , Água Corporal , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Rim/patologia , Medula Renal/patologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
10.
Am J Cardiol ; 118(7): 985-90, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27521223

RESUMO

The relative incidence of long-term adverse effects between low-osmolar contrast media (LOCM) and iso-osmolar contrast media (IOCM) after coronary angiography is still unclear. We analyzed cardiology patients undergoing coronary angiography from January 2006 to July 2013 using either LOCM (iohexol, iopromide) or IOCM (iodixanol) at a single institution. For each contrast medium, primary (all-cause mortality, n = 6,992) and secondary outcomes (long-term renal injury and cardiovascular events beyond 90 days, n = 2,792) were recorded. Inverse probability weighing (IPW) was applied to minimize the selection bias between groups. Unadjusted all-cause mortality was significantly lower for LOCM versus IOCM (hazard ratio [HR] 0.28, 95% CI 0.23 to 0.34). After multivariate Cox regression or IPW, all-cause mortality became comparable and lost statistical significance. Chronic kidney disease subgroup had higher mortality risk when receiving LOCM compared with IOCM (regression adjusted HR 1.80, 95% CI 0.95 to 3.42; IPW-adjusted HR 1.57, 95% CI 0.99 to 2.48). In conclusion, after coronary angiography, patients receiving LOCM had comparable overall long-term mortality compared with IOCM after adjustment. LOCM tended to induce higher long-term mortality than IOCM in chronic kidney disease cohorts.


Assuntos
Meios de Contraste , Angiografia Coronária , Insuficiência Cardíaca/epidemiologia , Mortalidade , Infarto do Miocárdio/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Causas de Morte , China/epidemiologia , Feminino , Humanos , Incidência , Iohexol/análogos & derivados , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Concentração Osmolar , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Ácidos Tri-Iodobenzoicos
11.
Sci Rep ; 5: 16951, 2015 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-26581247

RESUMO

Matrix metalloproteinases (MMPs) exert a dual effect in ischemic stroke and thus represent an ideal target for detection and therapy. However, to date, all clinical trials of MMP inhibitors have failed, and alternative drug candidates and therapeutic targets are urgently required. Nonetheless, further investigations are limited by the lack of non-invasive imaging techniques. Here, we report a novel, fast and ultrasensitive MMP activatable optical imaging probe for the dynamic visualization of MMP activity in photothrombotic stroke mice. This probe provides a significant signal enhancement in as little as 15 min, with the highest signal intensity occurring at 1 h post-injection, and shows high sensitivity in measuring MMP activity alterations, which makes it specifically suitable for the real-time visualization of MMP activity and drug discovery in preclinical research. Moreover, using this probe, we successfully demonstrate that the regulation of the p38 mitogen-activated protein kinase (MAPK) signal pathway is capable of modulating MMP activity after stroke, revealing a novel regulatory mechanism of postischemic brain damage and overcoming the limitations of traditional therapeutic strategies associated with MMP inhibitors by using a non-invasive molecular imaging method.


Assuntos
Luz , Metaloproteinases da Matriz/metabolismo , Sondas Moleculares/metabolismo , Acidente Vascular Cerebral/enzimologia , Acidente Vascular Cerebral/etiologia , Trombose/complicações , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Ativação Enzimática/efeitos dos fármacos , Masculino , Inibidores de Metaloproteinases de Matriz/farmacologia , Camundongos Endogâmicos C57BL , Recuperação de Função Fisiológica/efeitos dos fármacos , Espectroscopia de Luz Próxima ao Infravermelho , Acidente Vascular Cerebral/fisiopatologia , Trombose/patologia , Distribuição Tecidual/efeitos dos fármacos
12.
CNS Neurosci Ther ; 21(11): 877-86, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26384586

RESUMO

AIMS: We tested the hypothesis that endothelial progenitor cell (EPC)-mediated functional recovery after stroke may be associated with the endothelial nitric oxide synthase (eNOS)/brain-derived neurotrophic factor (BDNF) signaling pathway. METHODS: Mice were infused with either EPCs or saline after being subjected to middle cerebral artery occlusion. The EPC-treated mice also received intravenous injections of either Nω-nitro-l-arginine methyl ester (L-NAME, the NOS inhibitor) or saline. RESULTS: The activation of eNOS and the expression of BDNF were significantly increased in ischemic brain of the EPC-treated mice, along with increased angiogenesis and neurogenesis. On diffusion tensor imaging (DTI), significant increases in fractional anisotropy and fiber count were observed in white matter, indicating axonal growth stimulated by EPCs. However, the EPC-treated mice that were received an L-NAME injection failed to exhibit the observed increases in angiogenesis, neurogenesis, and axonal growth. In addition, the neurons cocultured with EPCs in vitro exhibited the increased expression of BDNF and decreased apoptosis after oxygen-glucose deprivation compared with the control group. This EPC-induced protective effect was virtually absent in the L-NAME treatment group. CONCLUSION: The eNOS/BDNF pathway may be involved in the EPC-mediated functional recovery of stroke mice. DTI is feasible for dynamically tracking the orientation of axonal projections after EPC treatment.


Assuntos
Transplante de Medula Óssea/métodos , Células Progenitoras Endoteliais/fisiologia , Células Progenitoras Endoteliais/transplante , Infarto da Artéria Cerebral Média/cirurgia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Inibidores Enzimáticos/uso terapêutico , Proteína Glial Fibrilar Ácida/metabolismo , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NG-Nitroarginina Metil Éster/uso terapêutico , Neovascularização Patológica/etiologia , Neovascularização Patológica/terapia , Doenças do Sistema Nervoso/etiologia , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Neurônios/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfopiruvato Hidratase/metabolismo , Fatores de Tempo
13.
Stroke ; 46(7): 1938-46, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26045601

RESUMO

BACKGROUND AND PURPOSE: An immature vascular phenotype in diabetes mellitus may cause more severe vascular damage and poorer functional outcomes after stroke, and it would be feasible to repair damaged functional vessels using endothelial progenitor cell (EPC) transplantation. However, high glucose induces p38 mitogen-activated protein kinase activation, which can accelerate the senescence and apoptosis of EPCs. The aim of this study was to investigate the combined effects of EPC transplantation and p38 mitogen-activated protein kinase inhibitor administration on diabetic stroke outcomes. METHODS: Bone marrow-derived EPCs were injected intra-arterially into db/db mice after ischemic stroke induction. RWJ 67657 (RWJ), a p38 mitogen-activated protein kinase inhibitor, was administered orally for 7 consecutive days, with the first dose given 30 minutes before stroke induction. Functional outcome was determined at days 0, 1, 7, 14, and 21. Angiogenesis, neurogenesis, infarct volume, and Western blotting assays were performed on day 7, and white matter remodeling was determined on day 14. RESULTS: Neither EPC transplantation nor RWJ administration alone significantly improved diabetic stroke outcome although RWJ displayed a potent anti-inflammatory effect. By both improving the functioning of EPCs and reducing inflammation, EPC transplantation plus RWJ administration in vivo synergistically promoted angiogenesis and neurogenesis after diabetic stroke. In addition, the white matter remodeling, behavioral scores, and expressions of vascular endothelial growth factor and brain-derived neurotrophic factor were significantly increased in diabetic mice treated with both EPCs and RWJ. CONCLUSIONS: The combination of EPC transplantation and RWJ administration accelerated recovery from diabetic stroke, which might have been caused by increased levels of proangiogenic and neurotrophic factors.


Assuntos
Isquemia Encefálica/terapia , Diabetes Mellitus Experimental/terapia , Células Progenitoras Endoteliais/transplante , Imidazóis/administração & dosagem , Piridinas/administração & dosagem , Transplante de Células-Tronco/métodos , Acidente Vascular Cerebral/terapia , Animais , Isquemia Encefálica/patologia , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Acidente Vascular Cerebral/patologia , Resultado do Tratamento
14.
Elife ; 4: e06576, 2015 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-25962854

RESUMO

Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus-hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Córtex Auditivo/fisiopatologia , Cerebelo/fisiopatologia , Hipocampo/fisiopatologia , Hiperacusia/fisiopatologia , Formação Reticular/fisiopatologia , Zumbido/fisiopatologia , Tonsila do Cerebelo/patologia , Animais , Córtex Auditivo/patologia , Mapeamento Encefálico , Cerebelo/patologia , Cóclea/patologia , Cóclea/fisiopatologia , Modelos Animais de Doenças , Corpos Geniculados/patologia , Corpos Geniculados/fisiopatologia , Hipocampo/patologia , Humanos , Hiperacusia/induzido quimicamente , Hiperacusia/patologia , Colículos Inferiores/patologia , Colículos Inferiores/fisiopatologia , Imagem por Ressonância Magnética , Modelos Psicológicos , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Agitação Psicomotora/patologia , Agitação Psicomotora/fisiopatologia , Ratos , Ratos Sprague-Dawley , Formação Reticular/patologia , Ácido Salicílico , Zumbido/induzido quimicamente , Zumbido/patologia
15.
Neural Plast ; 2015: 475382, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25734018

RESUMO

OBJECTIVE: Subjective tinnitus is hypothesized to arise from aberrant neural activity; however, its neural bases are poorly understood. To identify aberrant neural networks involved in chronic tinnitus, we compared the resting-state functional magnetic resonance imaging (fMRI) patterns of tinnitus patients and healthy controls. MATERIALS AND METHODS: Resting-state fMRI measurements were obtained from a group of chronic tinnitus patients (n = 29) with normal hearing and well-matched healthy controls (n = 30). Regional homogeneity (ReHo) analysis and functional connectivity analysis were used to identify abnormal brain activity; these abnormalities were compared to tinnitus distress. RESULTS: Relative to healthy controls, tinnitus patients had significant greater ReHo values in several brain regions including the bilateral anterior insula (AI), left inferior frontal gyrus, and right supramarginal gyrus. Furthermore, the left AI showed enhanced functional connectivity with the left middle frontal gyrus (MFG), while the right AI had enhanced functional connectivity with the right MFG; these measures were positively correlated with Tinnitus Handicap Questionnaires (r = 0.459, P = 0.012 and r = 0.479, P = 0.009, resp.). CONCLUSIONS: Chronic tinnitus patients showed abnormal intra- and interregional synchronization in several resting-state cerebral networks; these abnormalities were correlated with clinical tinnitus distress. These results suggest that tinnitus distress is exacerbated by attention networks that focus on internally generated phantom sounds.


Assuntos
Córtex Cerebral/fisiopatologia , Sincronização Cortical , Rede Nervosa/fisiopatologia , Zumbido/fisiopatologia , Adulto , Mapeamento Encefálico , Doença Crônica , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
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