RESUMO
Regular exercise improves several functions, including cognition, in patients with stroke. However, the effect of regular exercise on neurogenesis related to cognition remains doubtful. We investigated the most effective exercise intensity for functional recovery after stroke using RNA sequencing following regular treadmill exercise. Photothrombotic cerebral infarction was conducted for 10-week-old male Sprague-Dawley rats (n = 36). A Morris water maze (MWM) test was performed before a regular treadmill exercise program (5 days/week, 4 weeks). Rats were randomly divided into four groups: group A (no exercise); group B (low intensity, maximal velocity 18 m/min); group C (moderate intensity, maximal velocity 24 m/min) and group D (high intensity, maximal velocity 30 m/min). After 4 weeks, another MWM test was performed, and all rats were sacrificed. RNA sequencing was performed with ipsilesional hippocampal tissue. On the day after cerebral infarction, no differences in escape latency and velocity were observed among the groups. At 4 weeks after cerebral infarction, the escape latencies in groups B, C, and D were shorter than in group A. The escape latencies in groups B and C were shorter than in group D. The velocity in groups A, B, and C was faster than in group D. Thirty gene symbols related to neurogenesis were detected (p < 0.05, fold change > 1.0, average normalized read count > four times). In the neurotrophin-signaling pathway, the CHK gene was upregulated, and the NF-κB gene was downregulated in the low-intensity group. The CHK and NF-κB genes were both downregulated in the moderate-intensity group. The Raf and IRAK genes were downregulated in the high-intensity group. Western blot analysis showed that NF-κB expression was lowest in the moderate-intensity group, whereas CHK and Raf were elevated, and IRAK was decreased in the high-intensity group. Moderate-intensity exercise may contribute to neuroplasticity. Variation in the expression of neurotrophins in neurogenesis according to exercise intensity may reveal the mechanism of neuroplasticity. Thus, NF-κB is the key neurotrophin for neurogenesis related to exercise intensity.
Assuntos
Infarto Cerebral , Modelos Animais de Doenças , Neurogênese , Condicionamento Físico Animal , Ratos Sprague-Dawley , Animais , Neurogênese/genética , Infarto Cerebral/genética , Infarto Cerebral/metabolismo , Infarto Cerebral/fisiopatologia , Infarto Cerebral/patologia , Ratos , Masculino , Hipocampo/metabolismo , Regulação da Expressão GênicaRESUMO
Neuronal loss is a hallmark of stroke and other neurodegenerative diseases, and as such, neuronal loss caused by microglia has been thought to be a contributing factor to disease progression. Here, we show that microglia indeed contribute significantly to neuronal loss in a mouse model of stroke, but this microglial-dependent process of neuronal clearance specifically targets stressed and degenerating neurons in the ischemic cortical region and not healthy non-ischemic neurons. Nonspecific stimulation of microglia decreased the density of neurons in the ischemic cortical region, whereas specific inhibition of MFG-E8 signaling, which is required for microglial phagocytosis of neurons, had the opposite effect. In both scenarios, the effects were microglia specific, as the same treatments had no effect in mice whose microglia were depleted prior to stroke. Finally, even though the inhibition of MFG-E8 signaling increased neuronal density in the ischemic brain region, it substantially exacerbated the development of cortical infarction. In conclusion, microglia through MFG-E8 signaling contribute to the loss of ischemic neurons and, in doing so, minimize the development of cortical infarction after stroke.
Assuntos
Antígenos de Superfície , Microglia , Proteínas do Leite , Neurônios , Transdução de Sinais , Acidente Vascular Cerebral , Animais , Microglia/metabolismo , Microglia/patologia , Neurônios/metabolismo , Neurônios/patologia , Camundongos , Proteínas do Leite/metabolismo , Antígenos de Superfície/metabolismo , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/complicações , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Infarto Cerebral/patologia , Infarto Cerebral/metabolismo , Infarto Cerebral/etiologia , Encéfalo/metabolismo , Encéfalo/patologia , Fagocitose , Córtex Cerebral/metabolismo , Córtex Cerebral/patologiaAssuntos
Infarto Cerebral , Trombose Intracraniana , Imageamento por Ressonância Magnética , Trombose Venosa , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Trombose Venosa/patologia , Trombose Intracraniana/patologia , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/metabolismo , Adulto Jovem , Infarto Cerebral/patologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Cefaleia/etiologia , Córtex Cerebral/patologia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/diagnóstico por imagem , Diagnóstico Diferencial , Lobo Temporal/patologia , Lobo Temporal/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Convulsões/etiologia , Edema Encefálico/patologia , Lobo Frontal/patologia , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/irrigação sanguíneaRESUMO
Previous studies have reported various anatomical differences in the cerebral artery between healthy subjects and patients with posterior circulation cerebral infarction. In particular, basilar artery angulation has been associated with posterior circulation cerebral infarction. We compared anatomical variations and the degree of anterior and lateral vertebrobasilar artery angulation and deviation to compare the incidence of cerebral infarction of healthy subjects and patients with posterior circulation cerebral infarction. We compared basilar artery anatomy using brain magnetic resonance angiography in 97 patients who underwent brain magnetic resonance angiography during health checkups at our hospital and in 92 patients diagnosed with posterior circulation cerebral infarction between 2012 and 2022. Anatomical variations, including fetal-type posterior cerebral artery, hypoplastic P1 segment, vertebrobasilar dolichoectasia, and dominant vertebral artery, as well as the degree of anterior and lateral deviation and angulation, were evaluated. Correlations between these variations and the occurrence of cerebral infarction were analyzed. The prevalence of hypoplastic P1 was significantly differences in patients with posterior circulation cerebral infarction (odds ratio: 5.655). Furthermore, patients with posterior circulation cerebral infarction exhibited more acute anterior and lateral angulation, as well as lateral deviation. Hypoplastic P1 and more acute anterior or lateral angulation of the vertebrobasilar artery are associated with increased frequency of cerebral infarction.
Assuntos
Artéria Basilar , Infarto Cerebral , Angiografia por Ressonância Magnética , Artéria Vertebral , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Artéria Basilar/diagnóstico por imagem , Artéria Basilar/patologia , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/anormalidades , Artéria Vertebral/anatomia & histologia , Idoso , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Infarto Cerebral/epidemiologia , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/patologia , Adulto , Artéria Cerebral Posterior/diagnóstico por imagem , Variação AnatômicaRESUMO
Sickle cell disease (SCD)-related neurological effects are particularly devastating. Dilated perivascular spaces (dPVS) are a well-described component of cerebral small vessel disease in older adults without SCD. However, the burden and association of dPVS with neurological complications in children with SCD have not been described. In this study, we used the international consensus criteria to quantify dPVS in the centrum semiovale and basal ganglia in T2-weighted magnetic resonance images (MRI) of children with SCD who were randomized as part of the Silent Cerebral Infarct Transfusion (SIT) trial. We examined the relationship between global and/or regional dPVS burden and presence or area of silent cerebral infarctions, hematological measures, demographic variables, and full-scale intelligence quotient (FSIQ) scores. The study included 156 SIT trial participants who had pre-randomization and study exit MRI. Their median age was 9.6 (5-15) years, 39% were female, and 94 (60%) participants had a high dPVS burden. Participants randomized to the blood transfusion arm and who had a high dPVS burden at baseline had a moderate decline in dPVS score over 36 months compared to no change in the observation group. On multivariable logistic regression, intelligence quotient was not associated with dPVS burden. Children with SCD included in the SIT trial have a high burden of dPVS compared to children without SCD. However, dPVS do not appear to have the same pathophysiology of silent cerebral infarcts. Further study is needed to determine both their etiology and clinical relevance.
Assuntos
Anemia Falciforme , Imageamento por Ressonância Magnética , Humanos , Anemia Falciforme/complicações , Anemia Falciforme/patologia , Anemia Falciforme/terapia , Anemia Falciforme/diagnóstico por imagem , Feminino , Masculino , Criança , Pré-Escolar , Adolescente , Sistema Glinfático/diagnóstico por imagem , Sistema Glinfático/patologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Infarto Cerebral/patologiaRESUMO
Ischemic stroke followed by reperfusion (IR) leads to extensive cerebrovascular injury characterized by neuroinflammation and brain cell death. Inhibition of matrix metalloproteinase-3 (MMP-3) emerges as a promising therapeutic approach to mitigate IR-induced stroke injury. We employed middle cerebral artery occlusion with subsequent reperfusion (MCAO/R) to model ischemic stroke in adult mice. Specifically, we investigated the impact of MMP-3 knockout (KO) on stroke pathophysiology using RNA sequencing (RNA-seq) of stroke brains harvested 48 h post-MCAO. MMP-3 KO significantly reduced brain infarct size following stroke. Notably, RNA-seq analysis showed that MMP-3 KO altered expression of 333 genes (252 downregulated) in male stroke brains and 3768 genes (889 downregulated) in female stroke brains. Functional pathway analysis revealed that inflammation, integrin cell surface signaling, endothelial- and epithelial-mesenchymal transition (EndMT/EMT), and apoptosis gene signatures were decreased in MMP-3 KO stroke brains. Intriguingly, MMP-3 KO downregulated gene signatures more profoundly in females than in males, as indicated by greater negative enrichment scores. Our study underscores MMP-3 inhibition as a promising therapeutic strategy, impacting multiple cellular pathways following stroke.
Assuntos
Infarto Cerebral , Modelos Animais de Doenças , AVC Isquêmico , Metaloproteinase 3 da Matriz , Camundongos Knockout , Animais , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Masculino , Feminino , Camundongos , AVC Isquêmico/genética , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , Infarto Cerebral/genética , Infarto Cerebral/patologia , Infarto Cerebral/metabolismo , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Camundongos Endogâmicos C57BL , Transcriptoma , Regulação da Expressão Gênica , Encéfalo/metabolismo , Encéfalo/patologiaRESUMO
BACKGROUND: This study aimed to develop a modified histochemical staining technique to successfully identify arterial and venous segments of brain microvessels. NEW METHOD: Gelatin/red ink-alkaline phosphatase-oil red O (GIAO) staining was developed from the traditional gelatin-ink perfusion method. Oil red Chinese ink for brush writing and painting mixed with gelatin was used to label cerebral vascular lumens. Subsequently, alkaline phosphatase staining was used to label endothelial cells on the arterial segments of cerebral microvessels. Thereafter, the red ink color in vessel lumens was highlighted with oil red O staining. RESULTS: The arterial segments of the brain microvessels exhibited red lumens surrounded by dark blue walls, while the venous segments were bright red following GIAO staining. Meanwhile, the nerve fiber bundles were stained brownish-yellow, and the nuclei appeared light green under light microscope. After cerebral infarction, we used GIAO staining to determine angiogenesis features and detected notable vein proliferation inside the infarct core. Moreover, GIAO staining in conjunction with hematoxylin staining was performed to assess the infiltration of foamy macrophages. COMPARISON WITH EXISTING METHOD: Red Chinese ink enabled subsequent multiple color staining on brain section. Oil red O was introduced to improved the resolution and contrast between arterial and venous segments of microvessels. CONCLUSION: With excellent resolution, GIAO staining effectively distinguished arterial and venous segments of microvessels in both normal and ischemic brain tissue. GIAO staining, as described in the present study, will be useful for histological investigations of microvascular bed alterations in a variety of brain disorders.
Assuntos
Encéfalo , Microvasos , Coloração e Rotulagem , Animais , Coloração e Rotulagem/métodos , Encéfalo/irrigação sanguínea , Masculino , Veias Cerebrais , Gelatina , Corantes , Artérias Cerebrais/citologia , Tinta , Infarto Cerebral/patologia , Compostos Azo , CarbonoRESUMO
BACKGROUND: Angiogenesis is crucial in neuroprotection of secondary thalamic injury after cortical infarction. The p75 neurotrophin receptor (p75NTR) plays a key role in activating angiogenesis. However, the effects of p75NTR on angiogenesis in the thalamus after cortical infarction are largely unknown. Herein we investigate whether p75NTR facilitates angiogenesis to attenuate secondary thalamic damage via activating hypoxia-inducible factor 1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway mediated by Von Hippel-Lindau (VHL) after distal middle cerebral artery occlusion (dMCAO). METHODS: The male rat model of dMCAO was established. The effects of p75NTR on the angiogenesis was evaluated using RNA-sequencing, immunohistochemistry, western blot, quantitative real-time polymerase chain reaction, magnetic resonance imaging, behavior tests, viral and pharmacological interventions. RESULTS: We found that the p75NTR and vessel density were decreased in ipsilateral thalamus after dMCAO. The p75NTR-VHL interaction was reduced, which promoted the ubiquitination degradation of HIF-1α and reduced VEGF expression after dMCAO. Notably, p75NTR overexpression restrained the ubiquitination degradation of HIF-1α by inhibiting VHL-HIF-1α interaction, further promoted angiogenesis, increased cerebral blood flow of ipsilateral thalamus and improved neurological function after dMCAO. CONCLUSION: For the first time, we highlighted that the enhancement of p75NTR-VHL interaction promoted angiogenesis in attenuating secondary thalamic damage after dMCAO.
Assuntos
Infarto da Artéria Cerebral Média , Neovascularização Fisiológica , Ratos Sprague-Dawley , Tálamo , Animais , Masculino , Ratos , Tálamo/metabolismo , Tálamo/patologia , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Neovascularização Fisiológica/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Receptores de Fator de Crescimento Neural/metabolismo , Receptores de Fator de Crescimento Neural/genética , Infarto Cerebral/patologia , Angiogênese , Proteínas do Tecido Nervoso , Receptores de Fatores de CrescimentoRESUMO
BACKGROUND: We aim to identify the distinct lesion patterns and regions associated with functional outcome and inflammation in patients with acute ischemic stroke, and investigate whether the association between lesion patterns and functional outcome was mediated by inflammation. METHODS AND RESULTS: We performed nonnegative matrix factorization to derived low-dimensional lesion patterns (atoms), and Bayesian linear regression models were applied to explore the associations of lesion patterns with inflammatory factors including high-sensitivity C-reactive protein and interleukin-6, as well as functional outcome (defined as modified Rankin Scale score at 3 months). The difference distribution mean and 95% highest probability density interval (HPDI) were calculated. Mediation analysis was used to examine the mediating effects of inflammation on the relationships between lesion patterns and functional outcome. Seven lesion patterns were derived from 5914 patients with acute ischemic stroke. Lesion patterns distributed in the cortical regions were associated with inflammatory response, including atom 1 (interleukin-6: mean, 0.113 [95% HPDI, 0.073-0.162]; high-sensitivity C-reactive protein: mean, 0.082 [95% HPDI, 0.038-0.123]) and atom 4 (interleukin-6: mean, 0.113 [95% HPDI, 0.071-0.167]; high-sensitivity C-reactive protein: mean, 0.108 [95% HPDI, 0.058-0.165]). These lesion patterns were also significantly associated with functional outcome (atom 1: mean, 1.958 [95% HPDI, 1.538-2.383]; atom 4: mean, 2.245 [95% HPDI, 1.773-2.741]). Mediation analysis suggested that interleukin-6 explained 15.34% and 7.47% in the association of atom 1 and atom 4 with functional outcome, respectively. CONCLUSIONS: Certain lesion patterns that are associated with both inflammation and functional outcome of acute ischemic stroke, especially cortical infarction, may play a role in functional outcome through modulating inflammatory reactions.
Assuntos
Proteína C-Reativa , Inflamação , Interleucina-6 , AVC Isquêmico , Humanos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Prognóstico , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Pessoa de Meia-Idade , Interleucina-6/sangue , Biomarcadores/sangue , Teorema de Bayes , Imageamento por Ressonância Magnética , Infarto Cerebral/patologiaRESUMO
BACKGROUND: The evidence for the association between white matter hyperintensity (WMH) severity and neurological deterioration (ND) in patients with single subcortical infarction (SSI) remains unclear and whether the association between them is modified by anterior circulation parent artery steno-occlusion (PAS) is unknown. Herein, we aimed to prospectively investigate the internal relevance. METHODS: In this prospective study, the severity of WMH and PAS were assessed in 288 consecutive patients with anterior circulation SSI arriving at our hospital, a tertiary teaching hospital affiliated with Fudan University, 24 h after onset from January 2017 to December 2018. The multivariable logistic regression model was used to estimate the association between WMH severity and the risk of ND within 7 days after stroke onset as well as the interactive effect between WMH severity and PAS on ND among patients with SSI. RESULTS: PAS modified the association between WMH severity and ND among patients with SSI (pinteraction = .029). After multivariate adjustment, the odds ratios of moderate-severe WMH associated with ND were 1.61 (95% CI, 0.50-5.19; ptrend = .428) for patients with PAS, and 0.37 (95% CI, 0.14-0.97; ptrend = .043) for those without PAS. Adding WMH severity to conventional risk factors improved risk prediction for ND in patients without PAS (net reclassification improvement: 48.2%, p = .005; integrated discrimination index: 2.5%, p = .004) but not in those with PAS. CONCLUSION: There was a modified effect of PAS on the association between WMH severity and ND within 7 days after stroke onset among patients with anterior circulation SSI, which deserves more research attention. WMH was negatively associated with ND in anterior circulation SSI patients without PAS.
Assuntos
Substância Branca , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Idoso , Estudos Prospectivos , Imageamento por Ressonância Magnética , Índice de Gravidade de Doença , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologiaRESUMO
In translational animal study aimed at evaluation of the effectiveness of innovative methods for treating cerebral stroke, including regenerative cell technologies, of particular importance is evaluation of the dynamics of changes in the volume of the cerebral infarction in response to therapy. Among the methods for assessing the focus of infarction, MRI is the most effective and convenient tool for use in preclinical studies. This review provides a description of MR pulse sequences used to visualize cerebral ischemia at various stages of its development, and a detailed description of the MR semiotics of cerebral infarction. A comparison of various methods for morphometric analysis of the focus of a cerebral infarction, including systems based on artificial intelligence for a more objective measurement of the volume of the lesion, is also presented.
Assuntos
Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Animais , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/patologia , Inteligência ArtificialRESUMO
BACKGROUND: We aimed to investigate the association of characteristics of lenticulostriate artery (LSA) morphology and parental atheromatous disease (PAD) with single subcortical infarction (SSI) and to explore whether the LSA morphology is correlated with proximal plaque features in asymptomatic PAD. METHODS AND RESULTS: Patients with acute SSI were prospectively enrolled and classified as large- and small-SSI groups. The clinical data and imaging features of LSA morphology (branches, length, dilation, and tortuosity) and middle cerebral artery plaques (normalized wall index, remodeling index, enhancement degree, and hyperintense plaques) were evaluated. Logistic regression was performed to determine the association of large SSIs with morphologic features of LSAs and plaques. The Spearman correlation between the morphologic characteristics of LSAs and plaque features in asymptomatic PAD was analyzed. Of the 121 patients recruited with symptomatic PAD, 102 had coexisting asymptomatic contralateral PAD. The mean length of LSAs (odds ratio, 0.84 [95% CI, 0.73-0.95]; P=0.007), mean tortuosity of LSAs (odds ratio, 1.13 [95% CI, 1.05-1.22]; P=0.002), dilated LSAs (odds ratio, 22.59 [95% CI, 2.46-207.74]; P=0.006), and normalized wall index (odds ratio, 1.08 [95% CI, 1.01-1.15]; P=0.022) were significantly associated with large SSIs. Moreover, the normalized wall index was negatively correlated with the mean length of LSAs (r=-0.348, P<0.001), and the remodeling index was negatively correlated with the mean tortuosity of LSAs (r=-0.348, P<0.001) in asymptomatic PAD. CONCLUSIONS: Our findings suggest that mean length of LSAs, mean tortuosity of LSAs, dilated LSAs, and normalized wall index are associated with large SSIs. Moreover, plaque features in asymptomatic PAD are correlated with morphologic features of LSAs.
Assuntos
Placa Aterosclerótica , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Angiografia por Ressonância Magnética , Doença Cerebrovascular dos Gânglios da Base/diagnóstico por imagem , Doença Cerebrovascular dos Gânglios da Base/patologia , Doenças Assintomáticas , Angiografia Cerebral/métodosRESUMO
OBJECTIVE: Autonomic Nervous System (ANS) dysfunction may be involved in the pathogenesis of Cerebral Small Vessel Disease (CSVD). The study aimed to explore the relationship between Recent Small Subcortical Infarct (RSSI) and Blood Pressure Variability (BPV), and Heart Rate Variability (HRV). METHODS: A total of 588 patients from the CSVD registration research database of Henan Province were included in this study, and were divided into two groups according to the presence of RSSI. Clinical data, including demographic characteristics, disease history, laboratory indexes, 24-hour ambulatory blood pressure and electrocardiogram indicators, and imaging markers of CSVD, were collected. Univariate and binary logistic regression analyses were used to study the relationship between RSSI and indicators of laboratory, HRV and BPV in the CSVD population. RESULTS: Multivariate analysis showed that higher 24-hour mean Diastolic Blood Pressure (DBP)[Odds Ratios (OR)=1.083,95% Confidence Intervals (CI)=(1.038,1.129), p < 0.001], Standard Deviation (SD) of 24-hour DBP [OR=1.059,95%CI=(1.000,1.121), p = 0.049], nocturnal mean Systolic Blood Pressure (SBP) [OR=1.020,95%CI=(1.004,1.035), p = 0.012], nocturnal mean DBP [OR=1.025,95%CI=(1.009,1.040), p = 0.002] were independent risk factors for RSSI. In contrast, the decrease of the standard deviation of N-N intervals (SDNN) [OR=0.994,95%CI=(0.989,1.000), p = 0.035] was beneficial to the occurrence of RSSI. In addition, neutrophil counts [OR=1.138,95%CI=(1.030,1.258), p = 0.011], total cholesterol (TC) [OR=1.203,95%CI=(1.008,1.437), p = 0.041] and High-Density Lipoprotein (HDL) [OR=0.391, 95%CI=(0.195,0.786), p = 0.008] were also independently associated with the occurrence of RSSI. After adjusting for confounding factors, except for TC, the other factors remained associated with the occurrence of RSSI. CONCLUSION: Increased 24-hour mean DBP, nocturnal mean SBP and DBP, SD of 24-hour DBP and decreased SDNN were independently correlated with RSSI occurrence, suggesting that sympathetic overactivity plays a role in the pathogenesis of RSSI.
Assuntos
Doenças do Sistema Nervoso Autônomo , Infarto Cerebral , Doenças do Sistema Nervoso Autônomo/complicações , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/patologia , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico , Infarto Cerebral/patologia , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pressão Sanguínea , Frequência Cardíaca , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS. METHODS: We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS. RESULTS: CMI prevalence was 11.8% in DS, 4.7% in controls, and 17.5% in sporadic AD. In DS, CMI increased in prevalence with age and the AD clinical continuum, was clustered in the parietal lobes, and was associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. DISCUSSION: In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype. HIGHLIGHTS: This is the first study to assess cortical microinfarcts (assessed with 3T magnetic resonance imaging) in adults with Down syndrome (DS). We studied the prevalence of cortical microinfarcts in DS and its relationship with age, the Alzheimer's disease (AD) clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition. The prevalence of cortical microinfarcts was 11.8% in DS and increased with age and along the AD clinical continuum. Cortical microinfarcts were clustered in the parietal lobes, and were associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy.
Assuntos
Doença de Alzheimer , Síndrome de Down , Imageamento por Ressonância Magnética , Humanos , Síndrome de Down/patologia , Síndrome de Down/complicações , Síndrome de Down/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Doença de Alzheimer/patologia , Doença de Alzheimer/diagnóstico por imagem , Adulto , Idoso , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Prevalência , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/patologia , Angiopatia Amiloide Cerebral/complicações , Fatores de Risco , Córtex Cerebral/patologia , Córtex Cerebral/diagnóstico por imagemRESUMO
BACKGROUND: Exogenous neural cell transplantation may be therapeutic for stroke, cerebral ischemic injury. Among other mechanisms, increasing findings indicated circular RNAs (circRNAs) regulate the pathogenesis progression of cerebral ischemia. Mmu_circ_0015034 (circEfnb2) was upregulated in focal cortical infarction established by middle cerebral artery occlusion (MCAO) in mice. Our study was designed to probe the molecular mechanism of circEfnb2 in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal damage in cerebral ischemia. METHODS: We established an in vitro OGD/R cell model. CircEfnb2 and microRNA-202-5p (miR-202-5p) levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Lactate dehydrogenase (LDH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were assessed using specific kits. Tumor necrosis factor-α (TNF-α) and Interleukin-1ß (IL-1ß) levels were examined using an Enzyme-linked immunosorbent assay (ELISA). Flow cytometry analysis evaluated cell apoptosis. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), cleaved caspase 3, and Tumor necrosis factor receptor-associated factor 3 (TRAF3) were determined using Western blot assay. RESULTS: Overall, circEfnb2 was highly expressed whereas miR-202-5p was decreased in OGD/R-treated mouse hippocampal neuronal HT22 cells compared to normal controls (both p > 0.05). From an in vitro functional perspective, circEfnb2 knockdown attenuated an OGD/R-triggered neuronal injury compared to controls (p > 0.05). Mechanically, circEfnb2 acted as a sponge of miR-202-5p; downregulation of miR-202-5p annulled the inhibitory roles of circEfnb2 silencing in an OGD/R-caused neuronal injury model. Our analysis showed that miR-202-5p directly targeted TRAF3 as enhanced TRAF3 abolished the effects of miR-202-5p in the OGD/R-induced neuronal injury. In vivo, lentivirus with a short hairpin (sh)-circEfnb2 inhibited cerebral injury, when injected into cerebral cortex in MCAO mice (p > 0.05). CONCLUSION: Our results suggest that circEfnb2 deficiency may decrease OGD/R-induced HT22 cell damage by modulating the miR-202-5p/TRAF3 axis. This explanation may provide a new direction for cerebral infarction potential therapeutic targets.
Assuntos
Apoptose , Infarto Cerebral , MicroRNAs , RNA Circular , Fator 3 Associado a Receptor de TNF , Animais , Masculino , Camundongos , Infarto Cerebral/metabolismo , Infarto Cerebral/genética , Infarto Cerebral/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Glucose/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/patologia , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/genética , RNA Circular/genética , RNA Circular/metabolismo , Fator 3 Associado a Receptor de TNF/genética , Fator 3 Associado a Receptor de TNF/metabolismoAssuntos
Tálamo , Humanos , Tálamo/diagnóstico por imagem , Tálamo/patologia , Masculino , Imageamento por Ressonância Magnética , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/complicações , Infarto Encefálico/diagnóstico , Infarto Encefálico/patologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico , Infarto Cerebral/patologia , Idoso , Feminino , Doenças Talâmicas/diagnóstico por imagem , Doenças Talâmicas/complicações , Doenças Talâmicas/diagnóstico , Doenças Talâmicas/patologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Research has linked enlarged perivascular spaces (EPVS) to cerebral venous reflux (CVR) in patients with hypertensive intracerebral hemorrhage, but it is unclear whether this association exists in recent small subcortical infarct (RSSI) patients. OBJECTIVE: This study aimed to investigate the correlation between EPVS and CVR in patients with RSSI. METHOD: This study included 297 patients, selected from patients with RSSI in the lenticulostriate artery admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University. CVR was assessed by time-of-flight magnetic resonance angiography (TOF-MRA). The relationship between EPVS and CVR was studied using multiple logistic regression analysis. RESULTS: This study included patients with an average age of 59.84±12.27 years, including 201 males (67.7%). CVR was observed in 40 (13.5%) patients. Compared to the group without CVR, the proportions of male patients and patients with a history of smoking and drinking were higher in the CVR group. The proportions of high-grade EPVS in the centrum semiovale region [23 cases (57.5%) vs. 108 cases (42.0%), p =0.067] and the basal ganglia region [30 cases (75.0%) vs. 133 cases (51.8%), p =0.006] were higher in the CVR group. After multiple logistic regression analysis, high-grade EPVS in the basal ganglia region was still associated with CVR (OR, 2.68; 95% CI, 1.22-5.87;p=0.014). CONCLUSION: In the population with RSSI, EPVS in basal ganglia is significantly associated with CVR, suggesting a close relationship between venous dysfunction and the formation of EPVS.
Assuntos
Gânglios da Base , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/patologia , Idoso , Angiografia por Ressonância Magnética , Sistema Glinfático/diagnóstico por imagem , Sistema Glinfático/patologia , Veias Cerebrais/diagnóstico por imagem , Veias Cerebrais/patologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , AdultoRESUMO
BACKGROUND: The Mongolian gerbil is an excellent laboratory animal for preparing the cerebral ischemia model due to its inherent deficiency in the circle of Willis. However, the low incidence and unpredictability of symptoms are caused by numerous complex variant types of the circle. Additionally, the lack of an evaluation system for the cerebral ischemia/reperfusion (I/R) model of gerbils has shackled the application of this model. METHODS: We created a symptom-oriented principle and detailed neurobehavioral scoring criteria. At different time points of reperfusion, we analyzed the alteration in locomotion by rotarod test and grip force score, infarct volume by triphenyltetrazolium chloride (TTC) staining, neuron loss using Nissl staining, and histological characteristics using hematoxylin-eosin (H&E) straining. RESULTS: With a successful model rate of 56%, 32 of the 57 gerbils operated by our method harbored typical features of cerebral I/R injury, and the mortality rate in the male gerbils was significantly higher than that in the female gerbils. The successfully prepared I/R gerbils demonstrated a significant reduction in motility and grip strength at 1 day after reperfusion; formed obvious infarction; exhibited typical pathological features, such as tissue edema, neuronal atrophy and death, and vacuolated structures; and were partially recovered with the extension of reperfusion time. CONCLUSION: This study developed a new method for the unilateral common carotid artery ligation I/R model of gerbil and established a standardized evaluation system for this model, which could provide a new cerebral I/R model of gerbils with more practical applications.
Assuntos
Isquemia Encefálica , Animais , Masculino , Feminino , Gerbillinae/fisiologia , Isquemia Encefálica/patologia , Infarto Cerebral/patologia , Neurônios/patologia , ReperfusãoRESUMO
Soft tissue filler injections are among the most popular facial rejuvenation methods. Cerebral infarction and ophthalmic artery occlusion are rare and catastrophic complications, especially when facial cosmetic fillers are injected by inexperienced doctors. Radiologists and plastic surgeons need to increase their awareness of the complications associated with fillers, which allows early diagnosis and intervention to improve patient prognosis. Regarding the mechanism by which vascular occlusion occurs after facial filler injections, a retrograde embolic mechanism is currently the predominant theory. Numerous case reports have been presented regarding complications associated with injections of facial aesthetics. However, the small sample sizes of these studies did not allow for an adequate assessment of the clinical and imaging manifestations based on the location of the occlusion and the type of filler, and detailed elaboration of multiple cerebral infarctions is also lacking. Therefore, this study aimed to investigate the clinical and radiological features of severe cerebral and ocular complications caused by cosmetic facial filler injections. In addition, we discuss the pathogenesis, treatment, and prognosis of these patients. The clinical, computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) findings were described and analysed. Radiological examinations are crucial for demonstrating severe complications, and brain MRI is especially strongly suggested for patients with cosmetic filler-induced vision loss to identify asymptomatic cerebral infarctions. Extreme caution and care should be taken during facial injections by plastic surgeons.