RESUMO
OBJECTIVES: Gait disorder (GD) is a common problem in cerebral small vessel disease (CSVD). This study aimed to determine (1) the early characteristics of GD in CSVD, (2) cerebellar neuroimaging features related to GD in CSVD, and (3) the association of cognitive impairment with GD. METHODS: In total, 183 subjects were enrolled in this study: patients with CSVD with normal cognitive function (CSVD-NC) group (64 subjects), patients with CSVD with mild cognitive impairment (CSVD-MCI) group (66 subjects), and a healthy control (HC) group (53 subjects). The GD patterns were evaluated using the ReadyGo three-dimensional motion balance testing system. Meanwhile, we analyzed the cerebrum and cerebellum structurally and functionally. Correlation analyses were conducted among gait indicators, neuroimaging features, and neuropsychological tests. RESULTS: Both the CSVD-NC and CSVD-MCI groups had a reduced stride length, cortical atrophy in the left cerebellum VIIIb, and decreased functional connectivity between the left cerebellum VIIIb and left SFGmed compared with the HC group. In the correlation analysis, the gray matter probability of the left cerebellum VIIIb was closely related to stride length in the HC group. In the CSVD-MCI group, linguistic function, memory, and attention were significantly correlated with gait performance. CONCLUSION: Decreased stride length was the earliest characteristic of GD in CSVD. Structural and functional regulation of the left cerebellum VIIIb could play a particularly important role in early GD in CSVD.
Assuntos
Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Transtornos dos Movimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , MarchaRESUMO
BACKGROUND: Activation of microglial cells plays an important role in neuroinflammation after ischemic stroke. Inhibiting the activation of microglial cells has been suggested as a potential therapeutic approach in the treatment of ischemic stroke. METHODS: Oxygen-glucose deprivation in primary microglial cells and transient middle cerebral artery occlusion (MCAO) in C57BL/6 mice were used as the in vitro and in vivo ischemic stroke models. Microarray analysis was performed to investigate the overall impact of long non-coding RNAs (lncRNAs) on the inflammation status of microglial cells. RT-qPCR was used to evaluate the lncRNA levels and mRNA levels of cytokines and microglial cell markers. ELISA was taken to measure the level of cytokines. Immunofluorescence was used to observe the activation of microglial cells. Western blotting was performed to test the p65 phosphorylation. RESULTS: In this study, we showed that LncRNA-1810034E14Rik was significantly decreased in LPS-treated or oxygen-glucose deprivation-induced microglial cells. Overexpression of 1810034E14Rik decreased the infarct volume and alleviated brain damage in MCAO mice. 1810034E14Rik overexpression reduced the expression of inflammatory cytokines not only in ischemic stroke mice but also in oxygen-glucose deprivation-induced microglial cells. Moreover, 1810034E14Rik overexpression could suppress the activation of microglial cells and inhibit the phosphorylation of p65. CONCLUSIONS: LncRNA-1810034E14Rik plays an anti-inflammatory role in ischemic stroke and regulates p65 phosphorylation, making it a potential target for stroke treatment.
Assuntos
Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Microglia/metabolismo , Fosfoproteínas Fosfatases/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Transcrição RelA/metabolismo , Animais , Animais Recém-Nascidos , Hipóxia Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Glucose/deficiência , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise em Microsséries , Microglia/efeitos dos fármacos , Fosfoproteínas Fosfatases/genética , RNA Longo não Codificante/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologiaRESUMO
Treatment with sodium tanshinone IIA sulfonate (STS) may ameliorate blood-brain barrier (BBB) damage in acute ischemic stroke patients receiving recombinant tissue plasminogen activator (rt-PA) thrombolysis and improve stroke patients' outcome. This randomized, single-center, placebo-controlled clinical trial investigated the potential effects and underlying mechanisms of STS. Forty-two acute ischemic stroke patients receiving intravenous rt-PA thrombolysis were randomized to intravenous administration either with STS (60 mg/day) (n = 21) or with equivalent volume of saline as a placebo (n = 21) after randomization for 10 days. Clinical outcomes, computer tomography perfusion (CTP) imaging with permeability-surface area product (PS) maps and serum levels of BBB damage biomarkers, were compared between the two groups. The percentage of patients with excellent functional outcome indicated by a 90-day mRS ≤1 was significantly higher in the STS group than in the placebo group (p = 0.028). For patients with CTP imaging (n = 30), PS in the ipsilateral lesion (p = 0.034) and relative PS (p = 0.013) were significantly lower in the STS group than that in placebo. STS-treated patients also had lower levels of matrix metalloproteinase (MMP)-9 (p = 0.036) and claudin-5 (p = 0.026), but higher levels of tissue inhibitor of metalloproteinase (TIMP)-1 (p = 0.040) than those in the placebo group. Post-stroke STS treatment could improve neurologic functional outcomes for acute ischemic stroke patients following rt-PA treatment by reducing BBB leakage and damage, which might be mechanistically associated with MMP-9 inhibition.
