Ischaemic stroke in young adults: a global perspective

Boot, Esther M.; Ekker, Merel S.; Putaala, Jukka; Kittner, Steven J.; Leeuw, Frank‐Erik de; Tuladhar, Anil M.

doi:10.1136/jnnp-2019-322424

Cited by 191 publications

(180 citation statements)

References 87 publications

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“…Stroke remains a leading cause of adult disability and the demand for stroke rehabilitation services is growing (Stinear et al, 2020). Especially, ischemic stroke at young age is an increasing problem in both developing and developed countries due to rising incidence, high morbidity and mortality, and long-term psychological, physical, and social consequences (Boot et al, 2020). So further research is needed to better understand the underlying mechanisms of ischemic stroke and find more efficient treatment measures.…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

et al. 2020

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Background: Stroke remains a leading cause of adult disability and the demand for stroke rehabilitation services is growing, and Astragaloside IV (As IV), a primary bioactive compound of Radix Astragali: Astragalus mongholicus Bunge (Fabaceae), may be a promising stroke therapy. Methods: To access the effect of As IV on adult mice after ischemic stroke, a photochemical ischemia model was established on C57BL/6 mice, which were intravenously administered As IV for three consecutive days later. And then the cognitive benefits and hippocampal neurogenesis were evaluated by Morris Water Maze (MWM) test, Golgi staining, and immunohistochemical staining in vivo and in vitro. Furthermore, to find out the underlying mechanism, interleukin-17 (IL-17) knockout (KO) mice were used, through RNA sequence (RNA-seq) analysis and immunohistochemistry. Then the mechanism of neurogenesis promoted by As IV was observed by western blot both in vivo and in vitro. Specifically, As IV, recombinant mouse IL-17A and IL-17F, and Wingless/integrated (Wnt)-expressing virus was administered respectively in neural stem cells (NSCs), and then their diameters and protein expression of Nestin, IL-17, and Wnt pathway relevant protein, were measured in vitro. Results: Administering As IV resulted in significant amelioration of stroke-induced cognitive deficits. And more hippocampal neurons with normal morphology, significant increments in the length of the apical dendrites, and the density of their spines were observed in As IV-treated mice. Furthermore, the immunohistochemistry staining of DCX/ BrdU and Sox2/Nestin showed As IV could promote hippocampal neurogenesis and NSC proliferation after ischemic stroke, as well as in vitro. For the mechanism underlying, IL-17 expression was downregulated significantly by As IV treatment and knocking out IL-17 was associated with nervous regeneration and synapse repair according to the analysis of RNA-seq. Consistent to As IV treatment, knocking out IL-17 showed some promotion on hippocampal neurogenesis and proliferation of NSCs, with activating Wnt pathway after

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Section: Introductionmentioning

confidence: 99%

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

et al. 2020

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“…Stroke is defined as a leading cause of adult disability, due to its high morbidity and mortality and long-term psychological 1,2 . It is estimated that 15 million people in the world are affected by stroke every year, 5 million of which die and another 5 million suffer from long-term disability 3 .…”

Section: Introductionmentioning

confidence: 99%

Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

et al. 2020

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We aimed to investigate the exact effect of IL-17 on regulating neural stem cells (NSCs) stemness and adult neurogenesis in ischemic cortex after stroke, how Astragaloside IV(As-IV) regulated IL-17 expression and the underlying mechanism. Photochemical brain ischemia model was established and IL-17 protein expression was observed at different time after stroke in WT mice. At 3 days after stroke, when IL-17 expression peaked, IL-17 knock out (KO) mice were used to observe cell proliferation and neurogenesis in ischemic cortex. Then, As-IV was administered intravenously to assess cell apoptosis, proliferation, neurogenesis, and cognitive deficits by immunochemistry staining, western blots, and animal behavior tests in WT mice. Furthermore, IL-17 KO mice and As-IV were used simultaneously to evaluate the mechanism of cell apoptosis and proliferation after stroke in vivo. Besides, in vitro, As-IV and recombinant mouse IL-17A was administered, respectively, into NSCs culture, and then their diameters, viable cell proliferation and pathway relevant protein was assessed. The results showed knocking out IL-17 contributed to regulating PI3K/Akt pathway, promoting NSCs proliferation, and neurogenesis after ischemic stroke. Moreover, As-IV treatment helped inhibit neural apoptosis, promote the neurogenesis and eventually relieve mice anxiety after stroke. Unsurprisingly, IL-17 protein expression could be downregulated by As-IV in vivo and in vitro and they exerted antagonistic effect on neurogenesis by regulating Akt/GSK-3β pathway, with significant regulation for apoptosis. In conclusion, IL-17 exerts negative effect on promoting NSCs proliferation, neurogenesis and cognitive deficits after ischemic stroke, which could be reversed by As-IV.

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“…Overall, this study aims to (1) examine the north-to-south gradient in stroke incidence and their interaction with urban versus rural settings. Meanwhile, this project has an advantage of prospective cohort study-design to (2) analyze the potential attributable risk factors of the geographic variations in stroke incidence.…”

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confidence: 99%

Geographic Variations of Stroke Incidence in Chinese Communities: An 18-Year Prospective Cohort Study from 1997 to 2015

Xia

et al. 2020

J Stroke

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Background and Purpose As a leading cause of disability and death in China, stroke as well as its epidemiologic features have gained increasing attention. Prior studies, however, have overgeneralized the north-to-south gradient in China. Whether the differences exist across urban and rural areas remains unexplored. This study therefore aims to investigate the north-to-south gradient in stroke incidence across urban and rural China.Methods The present prospective cohort study analyzed data from the China Health and Nutrition Survey 1997 to 2015. By including 16,917 individuals from diverse social contexts, we calculated the age-standardized incidence of stroke across regions and the age-adjusted risk ratio (aRR). Cox proportional hazards models with time-varying covariates were employed to analyze variations in incident stroke.Results During the follow-up, age-standardized incidence of stroke ranged from 4.17 per 1,000 person-years (95% confidence interval [CI], 3.38 to 4.96) in the north region to 1.95 (95% CI, 1.60 to 2.30) in the south region (aRR, 2.04; 95% CI, 1.58 to 2.64; <i>P</i><0.001). The north-to-south gradient of stroke incidence was observed only in rural areas, but not in urban areas. Hierarchical modelling analyses further indicated that the regional differences could be mostly explained by the disparities in the prevalence of hypertension.Conclusions The present study extends the current evidence on the north-to-south gradient by demonstrating that the difference varied across urban and rural China. Our findings highlight the importance of hypertension management as the measure for alleviating regional differences in stroke incidence.

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Ischaemic stroke in young adults: a global perspective

Cited by 191 publications

References 87 publications

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

Geographic Variations of Stroke Incidence in Chinese Communities: An 18-Year Prospective Cohort Study from 1997 to 2015

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