RESUMO
BACKGROUND: Reversibility of the diffusion-weighted imaging (DWI) lesion means that not all of the DWI lesion represents permanently injured tissue. We investigated DWI reversibility and the association with thrombolysis, reperfusion and functional outcome in patients from the WAKE-UP trial (Efficacy and Safety of Magnetic Resonance Imaging-Based Thrombolysis in Wake-Up Stroke). METHODS: In this retrospective analysis of WAKE-UP, a randomized controlled trial (RCT) between September 2012 and June 2017 in Belgium, Denmark, France, Germany, Spain and United Kingdom, a convolutional neural network segmented the DWI lesions (b=1000 s/mm2) at baseline and follow-up (24 hours). We calculated absolute and relative DWI reversibility in 2 ways: first, a volumetric (baseline volume-24-hour volume >0) and second, a voxel-based (part of baseline lesion not overlapping with 24-hour lesion) approach. We additionally defined relative voxel-based DWI-reversibility >50% to account for coregistration inaccuracies. We calculated the odds ratio for reversibility according to treatment arm. We analyzed the association of reversibility with excellent functional outcome (modified Rankin Scale score of 0-1), in a multivariable model. RESULTS: In 363 patients, the median DWI volume was 3 (1-10) mL at baseline and 6 (2-20) mL at follow-up. Volumetric DWI reversibility was present in 19% (69/363) with a median absolute reversible volume of 1 mL (0-2) or 28% (14-50) relatively. Voxel-based DWI reversibility was present in 358/363 (99%) with a median absolute volume of 1 mL (0-2), or 22% (9-38) relatively. In 18% of the patients (67/363), relative voxel-based DWI reversibility >50% was present. Volumetric DWI reversibility and relative voxel-based DWI reversibility >50% was more frequent in patients treated with alteplase versus placebo (OR, 1.86 [95% CI, 1.09-3.17] and OR, 2.03 [95% CI, 1.18-3.50], respectively). Relative voxel-based DWI reversibility >50% was associated with excellent functional outcome (OR, 2.30 [95% CI, 1.17-4.51]). CONCLUSIONS: Small absolute volumes of DWI reversibility were present in a large proportion of randomized patients in the WAKE-UP trial. Reversibility was more often present after thrombolysis.
Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Imageamento por Ressonância Magnética , AVC Isquêmico/tratamento farmacológico , Terapia TrombolíticaRESUMO
Thrombosis can lead to a wide variety of life-threatening circumstances. As current thrombolytic drug screening models often poorly predict drug profiles, leading to failure of thrombolytic therapy or clinical translation, more representative clot substrates are necessary for drug evaluation. Utilizing a Chandler loop device to form clot analogs at high shear has gained popularity in stroke societies. However, shear-dependent clot microstructure has not been fully addressed and low shear conditions are often overlooked. We herein characterized the impact of wall shear rate (126 to 951 s-1) on clot properties in the Chandler loop. Different revolutions (20-60) per minute and tubing sizes (3.2 to 7.9 mm) were employed to create different sized clots to mimic various thrombosis applications. Increased shear resulted in decreased RBC counts (76.9 ± 4.3% to 17.6 ± 0.9%) and increased fibrin (10 to 60%) based on clot histology. Increased fibrin sheet morphology and platelet aggregates were observed at higher shear under scanning electron microscope. These results show the significant impact of shear and tubing size on resulting clot properties and demonstrate the capability of forming a variety of reproducible in-vivo-like clot analogs in the Chandler loop device controlling for simple parameters to tune clot characteristics.
Assuntos
Acidente Vascular Cerebral , Trombose , Humanos , Plaquetas , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapia , Fibrinolíticos , FibrinaRESUMO
Ischemic stroke continues to be one of the leading causes of death and disability in the adult population worldwide. The currently used pharmacological methods for the treatment of ischemic stroke are not effective enough and require the search for new tools and approaches to identify therapeutic targets and potential neuroprotectors. Today, in the development of neuroprotective drugs for the treatment of stroke, special attention is paid to peptides. Namely, peptide action is aimed at blocking the cascade of pathological processes caused by a decrease in blood flow to the brain tissues. Different groups of peptides have therapeutic potential in ischemia. Among them are small interfering peptides that block protein-protein interactions, cationic arginine-rich peptides with a combination of various neuroprotective properties, shuttle peptides that ensure the permeability of neuroprotectors through the blood-brain barrier, and synthetic peptides that mimic natural regulatory peptides and hormones. In this review, we consider the latest achievements and trends in the development of new biologically active peptides, as well as the role of transcriptomic analysis in identifying the molecular mechanisms of action of potential drugs aimed at the treatment of ischemic stroke.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , AVC Isquêmico/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Neuroproteção , Peptídeos/farmacologia , Peptídeos/uso terapêuticoRESUMO
BACKGROUND: Bilateral anterior thalamic symmetrical infarction is very rarely observed in clinical practice and has rarely been reported in the literature. In this paper we introduce a patient with bilateral anterior thalamic symmetrical infarction and discuss his symptoms, treatment process, and follow-up visit results, as well as the potential pathological mechanisms of the disease. CASE PRESENTATION: A 71-year-old male had a sudden cognitive decline four days prior to medical consultation. The patient's brain MRI showed symmetrical high signals in the anterior part of both sides of the thalamus. The patient's head MRV and immunological tests were normal, and we considered that this patient had a rare case of bilateral anterior thalamic infarction. After 10 days of anti-platelet aggregation that lowered blood lipids and improved circulation, the patient's symptoms significantly abated. Two years later, we found through telephone follow-up that the patient's symptoms had not relapsed substantially and that he was able to perform self-care, having only continued to suffer a slight decline in short-term memory. CONCLUSION: For patients with bilateral prethalamic lesions who have only acute cognitive impairment, if the lesions conform to the blood supply area of both thalamic nodular arteries and DWI shows a high signal, the diagnosis of acute cerebral infarction should be considered, and the standard treatment plan for cerebral infarction should be given as soon as possible.
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Acidente Vascular Cerebral , Tálamo , Masculino , Humanos , Idoso , Tálamo/patologia , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/patologia , ArtériasRESUMO
It is commonly asserted that MRI-derived lesion masks outperform CT-derived lesion masks in lesion-mapping analysis. However, no quantitative analysis has been conducted to support or refute this claim. This study reports an objective comparison of lesion-mapping analyses based on CT- and MRI-derived lesion masks to clarify how input imaging type may ultimately impact analysis results. Routine CT and MRI data were collected from 85 acute stroke survivors. These data were employed to create binarized lesion masks and conduct lesion-mapping analyses on simulated behavioral data. Following standard lesion-mapping analysis methodology, each voxel or region of interest (ROI) were considered as the underlying "target" within CT and MRI data independently. The resulting thresholded z-maps were compared between matched CT- and MRI-based analyses. Paired MRI- and CT-derived lesion masks were found to exhibit significant variance in location, overlap, and size. In ROI-level simulations, both CT and MRI-derived analyses yielded low Dice similarity coefficients, but CT analyses yielded a significantly higher proportion of results which overlapped with target ROIs. In single-voxel simulations, MRI-based lesion mapping was able to include more voxels than CT-based analyses, but CT-based analysis results were closer to the underlying target voxel. Simulated lesion-symptom mapping results yielded by paired CT and MRI lesion-symptom mapping analyses demonstrated moderate agreement in terms of Dice coefficient when systematic differences in cluster size and lesion overlay are considered. Overall, these results suggest that CT and MR-derived lesion-symptom mapping results do not reliably differ in accuracy. This finding is critically important as it suggests that future studies can employ CT-derived lesion masks if these scans are available within the appropriate time-window.
Assuntos
Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI) is a mature scanning technique. With high sensitivity in detecting cerebral infractions, it has become an essential part of the clinical evaluation of acute stroke. However, with the update in medical ideals and treatment, clinicians are now focusing on distinguishing between reversible and irreversible brain tissue damage rather than detecting ischaemic lesions alone. OBJECTIVE: We supposed that Diffusion Kurtosis Imaging (DKI) could classify heterogeneous DWI lesions, deepening the understanding of tissue injury. We systematically studied the different parameters of DKI in acute stroke patients in the literature. METHODS: We collected 41 patients (26 male, 15 female), including different infarctions with acute cerebral infarction in different brain regions. Of all patients, 20 were single-infarction, while others were multi-infarctions. In this paper, we categorized acute cerebral infarction lesions into two types according to the parametric characteristics of both DKI and DWI. Type I means the DKI and DWI were matched, and Type II means the DKI and DWI were mismatched. Based on each parametric map, the region of interest (ROI) is outlined in each most severe lesion area (as large as possible in the center of the lesion). In the control group, ROIs of the same size are located in the corresponding regions of the contralateral hemisphere. RESULTS: In both Type I and Type II, all parameters conform to a normal distribution. An independent sample T-test was used to compare the differences between each group. In Type I, we found the FA, MD, Da, Dr, MK and Ka values were statistically different (P< 0.05), while in Type II, only the MK and Ka values were statistically different (P< 0.05). CONCLUSION: DKI, compared to DWI, can provide more imaging information about intracranial ischemic infarction, which can deepen the understanding of the mechanism of ischemic tissue damage. Our classification of the brain acute stroke lesions by DKI parameters and DWI may help us rediscover the real core of infraction.
Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/patologia , Doença Aguda , Infarto/patologia , Infarto Cerebral/diagnóstico por imagemRESUMO
BACKGROUND: White matter hyperintensities (WMH) are considered to contribute to diminished brain reserve, negatively impacting on stroke recovery. While WMH identified in the chronic phase after stroke have been associated with post-stroke aphasia, the contribution of premorbid WMH to the early recovery of language across production and comprehension has not been investigated. OBJECTIVE: To investigate the relationship between premorbid WMH severity and longitudinal comprehension and production outcomes in aphasia, after controlling for stroke lesion variables. METHODS: Longitudinal behavioral data from individuals with a left-hemisphere stroke were included at the early subacute (n = 37) and chronic (n = 28) stage. Spoken language comprehension and production abilities were assessed at both timepoints using word and sentence-level tasks. Magnetic resonance imaging (MRI) was performed at the early subacute stage to derive stroke lesion variables (volume and proportion damage to critical regions) and WMH severity rating. RESULTS: The presence of severe WMH explained an additional 18% and 25% variance in early subacute (t = -3.00, p = .004) and chronic (t = -3.60, P = .001) language comprehension abilities respectively, after controlling for stroke lesion variables. WMH did not predict additional variance of language production scores. CONCLUSIONS: Subacute clinical MRI can be used to improve prognoses of recovery of aphasia after stroke. We demonstrate that severe early subacute WMH add to the prediction of impaired longitudinal language recovery in comprehension, but not production. This emphasizes the need to consider different domains of language when investigating novel neurobiological predictors of aphasia recovery.
Assuntos
Afasia , Acidente Vascular Cerebral , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Afasia/etiologia , Afasia/complicações , Idioma , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Moyamoya is a disease with progressive cerebral arterial stenosis leading to stroke and silent infarct. Diffusion-weighted magnetic resonance imaging (dMRI) studies show that adults with moyamoya have significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) compared with controls, which raises concern for unrecognized white matter injury. Children with moyamoya have significantly lower FA and higher MD in their white matter compared with controls. However, it is unknown which white matter tracts are affected in children with moyamoya. METHODS: We present a cohort of 15 children with moyamoya with 24 affected hemispheres without stroke or silent infarct compared with 25 controls. We analyzed dMRI data using unscented Kalman filter tractography and extracted major white matter pathways with a fiber clustering method. We compared the FA, MD, AD, and RD in each segmented white matter tract and combined white matter tracts found within the watershed region using analysis of variance. RESULTS: Age and sex were not significantly different between children with moyamoya and controls. Specific white matter tracts affected included inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, thalamofrontal, uncinate fasciculus, and arcuate fasciculus. Combined watershed region white matter tracts in children with moyamoya had significantly lower FA (-7.7% ± 3.2%, P = 0.02) and higher MD (4.8% ± 1.9%, P = 0.01) and RD (8.7% ± 2.8%, P = 0.002). CONCLUSIONS: Lower FA with higher MD and RD is concerning for unrecognized white matter injury. Affected tracts were located in watershed regions suggesting that the findings may be due to chronic hypoperfusion. These findings support the concern that children with moyamoya without overt stroke or silent infarction are sustaining ongoing injury to their white matter microstructure and provide practitioners with a noninvasive method of more accurately assessing disease burden in children with moyamoya.
Assuntos
Lesões Encefálicas , Doença de Moyamoya , Acidente Vascular Cerebral , Substância Branca , Adulto , Humanos , Criança , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imagem de Tensor de Difusão/métodos , Acidente Vascular Cerebral/patologia , Doença de Moyamoya/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/patologiaAssuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: The use of a combination of stroke predictors, such as clinical factors and asymptomatic lesions on brain magnetic resonance imaging (MRI), may improve the accuracy of stroke risk prediction. Therefore, we attempted to develop a stroke risk score for healthy individuals. METHODS: We investigated the presence of cerebral stroke in 2365 healthy individuals who underwent brain dock screening at the Health Science Center in Shimane. We examined the factors that contributed to stroke and attempted to determine the risk of stroke by comparing background factors and MRI findings. RESULTS: The following items were found to be significant risk factors for stroke: age (≥60 years), hypertension, subclinical cerebral infarction, deep white matter lesion, and microbleeds. Each item was scored with 1 point, and the hazard ratios for the risk of developing stroke based on the group with 0 points were 17.2 (95% confidence interval [CI] 2.31-128) for 3 points, 18.1 (95% CI 2.03-162) for 4 points, and 102 (95% CI 12.6-836) for 5 points. CONCLUSIONS: A precise stroke prediction score biomarker can be obtained by combining MRI findings and clinical factors.
Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Pessoa de Meia-Idade , Prognóstico , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Fatores de Risco , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Isquemia Encefálica/patologia , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVES: This study aimed to investigate the association between electrocardiogram (ECG) abnormalities and silent vascular brain injury as defined by cerebral magnetic resonance imaging (MRI) in a stroke-free community-based population. METHODS: A total of 5888 participants were studied from the Cardiovascular Health Study (CHS), a prospective cohort of community-living older adults. Standard 12-lead ECGs measured prior to MRI scan were used. MRI scans were conducted at years 4-6 and 10-11. The primary outcome was presence of incident covert brain infarcts (CBIs) on the 2nd MRI examination, excluding previous CBIs and stroke occurrence. Secondary outcomes included white matter, ventricular, and sulcal atrophy on the 1st MRI. Logistic and multiple linear regression models were used to assess the relationship between ECG findings and silent vascular brain injury. RESULTS: Left axis deviation before MRI scan was related to presence of incident CBIs (odds ratio [OR]: 1.45; 95% CI: 1.01-2.08, p = .047). A long QT interval was associated with severe white matter hyperintensity (OR: 1.36; 95% CI: 1.04-1.77, p = .024). Minor Q and QS waves with ST-T abnormalities were positively related to sulcal atrophy (ß: 0.43, 95% CI: 0.06-0.81, p = .023). CONCLUSIONS: Our study found that ECG abnormalities were related to presence of CBIs, white matter hyperintensity, and sulcal atrophy on MRI in a stroke-free relderly population. Specifically, those with left axis deviation had an increased risk of presence of CBIs.
Assuntos
Traumatismo Cerebrovascular , Acidente Vascular Cerebral , Humanos , Idoso , Encéfalo/patologia , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/patologia , Infarto Encefálico , Traumatismo Cerebrovascular/patologia , Eletrocardiografia , Imageamento por Ressonância Magnética , Atrofia/patologia , Fatores de RiscoRESUMO
Listeria monocytogenes sometimes causes central nervous system infections. However, rhombencephalitis is a rare form of L. monocytogenes infection. Its clinical symptoms and magnetic resonance imaging (MRI) findings are often similar to those of vertebrobasilar stroke. We present the case of a 79-year-old woman with Listeria rhombencephalitis presenting with rhinorrhea and productive cough. She had giant cell arteritis (GCA) treated with prednisolone and methotrexate. She was admitted for loss of appetite, rhinorrhea, and productive cough. These symptoms were alleviated without specific treatment; however, she suddenly developed multiple cranial nerve palsies, and MRI showed hyperintense signals on diffusion-weighted imaging and hypointense signals on apparent diffusion coefficient in the brainstem. Ischemic stroke due to exacerbation of GCA was suspected, and treatment with intravenous methylprednisolone was initiated; however, seizures occurred, and a lumbar puncture was performed. Cerebrospinal fluid and blood cultures revealed L. monocytogenes, and she was diagnosed with Listeria rhombencephalitis. Although antibiotic treatment was continued, the patient died. Thus, when patients with rhinorrhea or productive cough develop sudden cranial nerve palsy, Listeria rhombencephalitis should be considered as a differential diagnosis, and lumbar puncture should be performed.
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Arterite de Células Gigantes , Listeria , Listeriose , Acidente Vascular Cerebral , Feminino , Humanos , Idoso , Listeriose/complicações , Listeriose/diagnóstico , Listeriose/tratamento farmacológico , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/patologia , Tosse , Rombencéfalo/patologia , Acidente Vascular Cerebral/patologiaRESUMO
A biopsy of gastrocnemius muscle from a patient with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome was studied histologically in semithin sections stained by hematoxylin-and-eosin (H&E) and toluidine blue, and ultrathin sections by transmission electron microscopy (TEM). H&E stain demonstrated typical ragged-red fibers (RRFs) and affected fibers in fascicles. Toluidine-blue stain showed an irregular meshwork in the center of RRFs. TEM demonstrated damaged myofibrils and variations in mitochondrial structure in RRFs and affected fibers. Dense mitochondria were compacted with cristae and pleomorphic electron-dense inclusions. Lucent mitochondria included paracrystalline inclusions with a parking lot appearance. At high magnification, the paracrystalline inclusions were composed of plates that paralleled and connected with mitochondrial cristae. These observations indicated that electron-dense granular and paracrystalline inclusions resulted from cristal degeneration and overlapping in mitochondria in MELAS syndrome.
Assuntos
Acidose Láctica , Síndrome MELAS , Acidente Vascular Cerebral , Humanos , Acidose Láctica/patologia , Síndrome MELAS/patologia , Acidente Vascular Cerebral/patologia , Músculo Esquelético/patologia , Mitocôndrias/patologiaRESUMO
Importance: The benefit of reperfusion therapies for acute ischemic stroke decreases over time. This decreasing benefit is presumably due to the disappearance of salvageable ischemic brain tissue (ie, the penumbra). Objective: To study the association between stroke onset-to-imaging time and penumbral volume in patients with acute ischemic stroke with a large vessel occlusion. Design, Setting, and Participants: A retrospective, multicenter, cross-sectional study was conducted from January 1, 2015, to June 30, 2022. To limit selection bias, patients were selected from (1) the prospective registries of 2 comprehensive centers with systematic use of magnetic resonance imaging (MRI) with perfusion, including both thrombectomy-treated and untreated patients, and (2) 1 prospective thrombectomy study in which MRI with perfusion was acquired per protocol but treatment decisions were made with clinicians blinded to the results. Consecutive patients with acute stroke with intracranial internal carotid artery or first segment of middle cerebral artery occlusion and adequate quality MRI, including perfusion, performed within 24 hours from known symptoms onset were included in the analysis. Exposures: Time from stroke symptom onset to baseline MRI. Main Outcomes and Measures: Penumbral volume, measured using automated software, was defined as the volume of tissue with critical hypoperfusion (time to maximum >6 seconds) minus the volume of the ischemic core. Substantial penumbra was defined as greater than or equal to 15 mL and a mismatch ratio (time to maximum >6-second volume/core volume) greater than or equal to 1.8. Results: Of 940 patients screened, 516 were excluded (no MRI, n = 19; no perfusion imaging, n = 59; technically inadequate perfusion imaging, n = 75; second segment of the middle cerebral artery occlusion, n = 156; unwitnessed stroke onset, n = 207). Of 424 included patients, 226 (53.3%) were men, and mean (SD) age was 68.9 (15.1) years. Median onset-to-imaging time was 3.8 (IQR, 2.4-5.5) hours. Only 16 patients were admitted beyond 10 hours from symptom onset. Median core volume was 24 (IQR, 8-76) mL and median penumbral volume was 58 (IQR, 29-91) mL. An increment in onset-to-imaging time by 1 hour resulted in a decrease of 3.1 mL of penumbral volume (ß coefficient = -3.1; 95% CI, -4.6 to -1.5; P < .001) and an increase of 3.0 mL of core volume (ß coefficient = 3.0; 95% CI, 1.3-4.7; P < .001) after adjustment for confounders. The presence of a substantial penumbra ranged from approximately 80% in patients imaged at 1 hour to 70% at 5 hours, 60% at 10 hours, and 40% at 15 hours. Conclusions and Relevance: Time is associated with increasing core and decreasing penumbral volumes. Despite this, a substantial percentage of patients have notable penumbra in extended time windows; the findings of this study suggest that a large proportion of patients with large vessel occlusion may benefit from therapeutic interventions.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Idoso , Feminino , AVC Isquêmico/diagnóstico por imagem , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Infarto da Artéria Cerebral Média , Estudos Retrospectivos , Estudos Prospectivos , Estudos Transversais , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , TrombectomiaRESUMO
The key component of stroke diagnosis is the localization and delineation of brain lesions, especially from MRI studies. Nonetheless, this manual delineation is time-consuming and biased by expert opinion. The main purpose of this study is to introduce an autoencoder architecture that effectively integrates cross-attention mechanisms, together with hierarchical deep supervision to delineate lesions under scenarios of remarked unbalance tissue classes, challenging geometry of the shape, and a variable textural representation. This work introduces a cross-attention deep autoencoder that focuses on the lesion shape through a set of convolutional saliency maps, forcing skip connections to preserve the morphology of affected tissue. Moreover, a deep supervision training scheme was herein adapted to induce the learning of hierarchical lesion details. Besides, a special weighted loss function remarks lesion tissue, alleviating the negative impact of class imbalance. The proposed approach was validated on the public ISLES2017 dataset outperforming state-of-the-art results, achieving a dice score of 0.36 and a precision of 0.42. Deeply supervised cross-attention autoencoders, trained to pay more attention to lesion tissue, are better at estimating ischemic lesions in MRI studies. The best architectural configuration was achieved by integrating ADC, TTP and Tmax sequences. The contribution of deeply supervised cross-attention autoencoders allows better support the discrimination between healthy and lesion regions, which in consequence results in favorable prognosis and follow-up of patients.
Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Photothrombotic (PT) stroke model is a reliable method to induce ischemic stroke in the target site using the excitation of photosensitive agents such as Rose Bengal (RB) dye after light illumination. Here, we performed a PT-induced brain ischemic model using a green laser and photosensitive agent RB and confirmed its efficiency through cellular, histological, and neurobehavioral approaches. METHODS: Mice were randomly allocated into RB; Laser irradiation; and RB + Laser irradiation groups. Mice were exposed to a green laser at a wavelength of 532 nm and intensity of 150 mW in a mouse model after injection of RB under stereotactic surgery. The pattern of Hemorrhagic and ischemic changes were evaluated throughout the study. The volume of the lesion site was calculated using unbiased stereological methods. For investigation of neurogenesis, we performed double - (BrdU/NeuN) immunofluorescence (IF) staining on day 28 following the last- BrdU injection. To assess the effect and quality of ischemic stroke on neurological behavior, the Modified neurological severity score (mNSS) test was done on days 1, 7, 14, and 28 days after stroke induction. RESULTS: Laser irradiation plus RB induced hemorrhagic tissue and pale ischemic changes over the 5 days. In the next few days, microscopic staining revealed neural tissue degeneration, demarcated necrotic site, and neuronal injury. BrdU staining showed a significant number of proliferating cells in the periphery of the lesion site in the Laser irradiation plus RB group compared to the group (p < 0.05) while the percent of NeuN+ cells per BrdU- positive cells was reduced. Also, prominent astrogliosis was observed in the periphery of irradiated sites on day 28. Neurological deficits were detected in mice from Laser irradiation plus the RB group. No histological or functional deficits were detected in RB and Laser irradiation groups. CONCLUSIONS: Taken together, our study showed cellular and histologic pathological changes which are associated with the PT induction model. Our findings indicated that the undesirable microenvironment and inflammatory conditions could affect neurogenesis concomitantly with functional deficits. Moreover, this research showed that this model is a focal, reproducible, noninvasive and accessible stroke model with a distinctive demarcation similar to human stroke conditions.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Camundongos , Animais , Bromodesoxiuridina/farmacologia , Acidente Vascular Cerebral/patologia , Neurônios/patologia , Neurogênese , Modelos Animais de Doenças , Isquemia Encefálica/patologiaRESUMO
Acute ischemic stroke (AIS) is associated with high rates of disability and mortality, exerting a substantial impact on overall survival and health-related quality of life. Treatment of AIS remains challenging given that the underlying pathologic mechanisms remain unclear. However, recent research has demonstrated that the immune system plays a key role in the development of AIS. Numerous studies have reported infiltration of T cells into ischemic brain tissue. While some types of T cells can promote the development of inflammatory responses and aggravate ischemic damage in patients with AIS, other T cells appear to exert neuroprotective effects via immunosuppression and other mechanisms. In this review, we discuss the recent findings regarding the infiltration of T cells into ischemic brain tissue, and the mechanisms governing how T cells can facilitate tissue injury or neuroprotection in AIS. Factors influencing the function of T cells, such as intestinal microflora and sex differences, are also discussed. We also explore the recent research on the effect of non-coding RNA on T cells after stroke, as well as the potential for specifically targeting T cells in the treatment of stroke patients.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Qualidade de Vida , Linfócitos T/patologia , Acidente Vascular Cerebral/patologia , Isquemia Encefálica/complicações , IsquemiaRESUMO
Stroke causes varying degrees of neurological deficits, leading to corresponding dysfunctions. There are different therapeutic principles for each stage of pathological development. Neuroprotection is the main treatment in the acute phase, and functional recovery becomes primary in the subacute and chronic phases. Neuroplasticity is considered the basis of functional restoration and neurological rehabilitation after stroke, including the remodeling of dendrites and dendritic spines, axonal sprouting, myelin regeneration, synapse shaping, and neurogenesis. Spatiotemporal development affects the spontaneous rewiring of neural circuits and brain networks. Microglia are resident immune cells in the brain that contribute to homeostasis under physiological conditions. Microglia are activated immediately after stroke, and phenotypic polarization changes and phagocytic function are crucial for regulating focal and global brain inflammation and neurological recovery. We have previously shown that the development of neuroplasticity is spatiotemporally consistent with microglial activation, suggesting that microglia may have a profound impact on neuroplasticity after stroke and may be a key therapeutic target for post-stroke rehabilitation. In this review, we explore the impact of neuroplasticity on post-stroke restoration as well as the functions and mechanisms of microglial activation, polarization, and phagocytosis. This is followed by a summary of microglia-targeted rehabilitative interventions that influence neuroplasticity and promote stroke recovery.
Assuntos
Microglia , Acidente Vascular Cerebral , Humanos , Microglia/patologia , Acidente Vascular Cerebral/patologia , Encéfalo/patologia , Neurogênese , Plasticidade NeuronalRESUMO
BACKGROUND: Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients' lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. METHODS: Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. RESULTS: Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. CONCLUSION: This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.
