Evolution pattern estimated by computed tomography perfusion post-thrombectomy predicts outcome in acute ischemic stroke.

OBJECTIVES: Computed tomography perfusion (CTP) and computed tomography angiography (CTA) have been recommended to select acute ischemic stroke (AIS) patients for endovascular thrombectomy (EVT) but are not widely used for post-treatment evaluation. We aimed to observe abnormalities in CTP and CTA before and after EVT and evaluate post-EVT CTP and CTA as potential tools for improving clinical outcome prediction. METHODS: Patients with AIS who underwent EVT and received CTP and CTA before and after EVT were retrospectively evaluated. The ischemic core was defined as the volume of relative cerebral blood flow <30% and hypoperfusion as the volume of Tmax >6 s. A reduction in hypoperfusion volume >90% between baseline and post-EVT CTP was defined as tissue optimal reperfusion (TOR). The 90-day modified Rankin scale was used to evaluate the clinical outcome. RESULTS: Eighty-three patients were included. Patients with an absent ischemic core or with TOR after EVT had a higher rate of modified Thrombolysis in Cerebral Ischemia score 2c-3 and recanalization of post-treatment vessel condition based on follow-up CTA. Multivariable logistic regression revealed that the baseline ischemic core volume (OR:0.934, p=0.009), TOR (OR:8.322, p=0.029) and immediate NIHSS score after EVT (OR:0.761, p=0.012) were factors significantly associated with good clinical outcome. Combining baseline ischemic core volume and TOR with immediate NIHSS score after EVT showed greatest performance for good outcome prediction after EVT(AUC=0.921). CONCLUSIONS: The addition of pretreatment and post-treatment CTP information to purely clinical NIHSS scores might help to improve the efficacy for good outcome prediction after EVT.

Multidelay Arterial Spin Labeling Versus Computed Tomography Perfusion in Penumbra Volume of Acute Ischemic Stroke.

BACKGROUND: Multidelay arterial spin labeling (ASL) is a novel perfusion method of ASL, with arterial transit time (ATT) calculated by multiple postlabeling delays to correct cerebral blood flow (CBF). We verify the accuracy of multidelay ASL in evaluating the ischemic penumbra and perfusion levels in patients with acute ischemic stroke, compared with computed tomography perfusion (CTP). METHODS: Patients with acute ischemic stroke with anterior circulation large vessel occlusion received baseline CTP, multidelay ASL, and diffusion-weighted imaging (DWI) in succession. Multidelay ASL image was processed to reconstruct ATT, CBF without ATT correction, and CBF corrected by ATT. The consistency of hypoperfusion and ischemic penumbra volume calculated by CTP and multidelay ASL were quantified by intraclass correlation coefficient (ICC) in 2-way mixed effects, absolute agreement, and single measure. Wilcoxon signed-rank test was used to compare the difference in penumbra volume between CTP, corrected ASL, and uncorrected ASL. RESULTS: Thirty patients were included. Hypoperfusion volume based on multidelay ASL with different thresholds were 117.95 (87.77-151.49) mL for corrected relative CBF<40%, 130.29 (85.99-249.37) mL for CBF corrected by ATT<20 mL·100g-1·min-1, no statistical difference (P>0.05) compared with the volume of CTP, and consistency was almost excellent (ICC, 0.91) and substantial consistent (ICC, 0.727). The volumes of ischemic penumbra were 91.00 (42.68-125.27) mL for corrected relative CBF<40%-DWI, 108.94 (62.03-150.86) mL for CBF corrected by ATT<20 mL·100 g-1·min-1-DWI, which showed no statistical difference compared with the penumbra volume of CTP (P>0.05). The consistency was excellent (ICC, 0.822) and moderate (ICC, 0.501), respectively. The volume of uncorrected relative CBF <40%-DWI was 209.57 (123.21-292.45) mL, statistically larger than corrected relative CBF <40%-DWI (P<0.001) and CTP (P<0.001). The volume of uncorrected CBF<20 mL·100g-1·min-1-DWI was 186.23 (86.56-298.22) mL, statistically larger than CBF corrected by ATT<20 mL·100g-1·min-1-DWI (P<0.001) and CTP(P<0.001). CONCLUSIONS: The volume of ischemic penumbra determined by CBF/DWI mismatch based on multidelay ASL is consistent with CTP. The penumbra volume calculated by CBF adjusted by ATT is more accurate.

Maternal RND3/RhoE deficiency impairs placental mitochondrial function in preeclampsia by modulating the PPARγ-UCP2 cascade.

Preeclampsia (PE) is a life-threatening disease of pregnant women associated with severe hypertension, proteinuria, or multi-organ injuries. Mitochondrial-mediated placental oxidative stress plays a key role in the pathogenesis of PE. However, the underlying mechanism remains to be revealed. Here, we identify Rnd3, a small Rho GTPase, regulating placental mitochondrial reactive oxygen species (ROS). We showed that Rnd3 is down-regulated in primary trophoblasts isolated from PE patients. Loss of Rnd3 in trophoblasts resulted in excessive ROS generation, cell apoptosis, mitochondrial injury, and proton leakage from the respiratory chain. Moreover, Rnd3 overexpression partially rescues the mitochondrial defects and oxidative stress in human PE primary trophoblasts. Rnd3 physically interacts with the peroxisome proliferators-activated receptor γ (PPARγ) and promotes the PPARγ-mitochondrial uncoupling protein 2 (UCP2) cascade. Forced expression of PPARγ rescues deficiency of Rnd3-mediated mitochondrial dysfunction. We conclude that Rnd3 acts as a novel protective factor in placental mitochondria through PPARγ-UCP2 signaling and highlight that downregulation of Rnd3 is a potential factor involved in PE pathogenesis.

The predictive role of early inflammation and oxidative stress and the dynamics of cytokines networks in post-stroke depression.

BACKGROUNDS: Chronic inflammation and oxidative stress play an important role in the pathogenesis of PSD. The main purposes of this study were to examine the dynamic changes of cytokines networks in PSD and the predictive role of early inflammation and oxidative stress for 2-week PSD. METHODS: Patients with ischemic stroke were recruited on day 3, and those with Hamilton Depression Rating Scale 24-Item (HAMD-24) ≥8 were classified as ischemic stroke patients with depressive symptoms and others as ischemic stroke patients without depressive symptoms. Subjects were then followed up at 2 weeks and 3 months, with those meeting diagnostic criteria for depressive symptoms on the HAMD ≥8 and the Statistical Manual of Mental Disorders-V (DSM-V) as the PSD group, and the others as the non-PSD group. RESULTS: At 3 days, IFN-γ, IL-12(p70), IL-12(p40), IL-2, IL-28A/IFNλ2, and IL-19 were elevated in ischemic stroke patients with depressive symptoms. At 2 weeks, IL-12(p40), IL-19, IL-22, IFN-ß and MMP-1 all were increased in PSD patients. At 3 months, IL-2, IFN-ß and sCD163 increased in PSD group. Longitudinally, the inflammatory response decreased significantly in PSD group from 2 weeks to 3 months of follow-up, while it gradually decreased in non-PSD group from 3 days to 3 months of follow-up. SOD was positively related to IL-12(p70), IFN-γ and IL-20. Plasma IFN-γ at 3 days may be a potential predictive biomarker for 2-week PSD. CONCLUSIONS: Peripheral inflammation and oxidative stress are involved in the pathogenesis of PSD, providing new insights for its diagnosis and treatment.

The mediating role of childhood maltreatment in the association between residence migration and adolescent depression.

BACKGROUND: It is well established that residence migration can negatively affect the mental health of adolescents. However, the related factors that mediate the association between residence migration and depression are still uncertain. METHODS: The participants were 16,037 adolescents in junior middle schools. A self-administered questionnaire was used for the survey. In addition to collecting general demographic characteristics of the participants, including age, gender, local residence status, only child status, parental marriage status and parent-child relationship, the questionnaire also contained the 9-item Patient Health Questionnaire, the short form of the Childhood Trauma Questionnaire and the Connor-Davidson Resilience Scale. Data analysis was conducted using SPSS software. RESULTS: A total of 14,059 valid questionnaires were collected, resulting in 12,122 local adolescents, defined as being born and raised locally, and 1937 migrant adolescents, defined as being transferred from other regions. Meanwhile, 53.3 % of local adolescents and 58.2 % of migrant adolescents reported depressive symptoms. This result indicated that residence migration might contribute to depression symptoms(OR = 1.136, 95%CI: 1.013-1.273, p < 0.05). Childhood maltreatment and parental divorce are risk factors for depression in migrant adolescents. For all adolescents, resilience and a good parent-child relationship may reduce the risk of depression. Childhood maltreatment completely mediates residence migration-related depression(95 % bootstrap CI = 0.146, 0.323). CONCLUSION: This study revealed that residence migration could contribute to adolescent depression, and childhood maltreatment may largely mediate this process, providing new insight into the relationship between adolescent depressive symptoms and residence migration. Reducing childhood maltreatment may effectively improve the depressive symptoms of migrant adolescents.

Metabolic Alterations and Related Biological Functions of Post-Stroke Depression in Ischemic Stroke Patients.

Background: Post-stroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. However, the underlying mechanisms of PSD remain ambiguous, and no objective diagnosis tool is available to diagnose PSD. Previous metabolomic studies on PSD included patients with ischemic and hemorrhagic stroke indiscriminately, which is not conducive to elucidating and predicting the occurrence of PSD. The aim of this study is to elucidate the pathogenesis of PSD and provide potential diagnostic markers for PSD in ischemic stroke patients. Methods: In total, 51 ischemic stroke patients at 2 weeks were included in this study. Those with depressive symptoms were assigned to the PSD group, while the others were assigned to the non-PSD group. Plasma metabolomics based on liquid chromatography-mass spectrometry (LC-MS) was performed to explore the differential plasma metabolites between the PSD and non-PSD groups. Results: Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) showed significant metabolic alterations between PSD patients and non-PSD patients. In total, 41 differential metabolites were screened out, mainly including phosphatidylcholines (PCs), L-carnitine and acyl carnitines, succinic acid, pyruvic acid and L-lactic acid. Metabolite-related pathway analysis revealed that alanine, aspartate and glutamate metabolism, glycerophospholipid metabolism and the citrate cycle (TCA cycle) may contribute to the pathogenesis of PSD. A panel of three signature metabolites [PC(22:5(7Z,10Z,13Z,16Z,19Z)/15:0), LysoPA(18:1(9Z)/0:0) and 1,5-anhydrosorbitol] was determined as potential biomarkers for PSD in ischemic stroke patients. Conclusion: These findings are conducive to providing new insights into the pathogenesis of PSD and developing objective diagnostic tools for PSD in ischemic stroke patients.

Temporal trend and attributable risk factors of stroke burden in China, 1990-2019: an analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Understanding the temporal trend of the disease burden of stroke and its attributable risk factors in China, especially at provincial levels, is important for effective prevention strategies and improvement. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is to investigate the disease burden of stroke and its risk factors at national and provincial levels in China from 1990 to 2019. METHODS: Following the methodology in the GBD 2019, the incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of stroke cases in the Chinese population were estimated by sex, age, year, stroke subtypes (ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage), and across 33 provincial administrative units in China from 1990 to 2019. Attributable mortality and DALYs of underlying risk factors were calculated by a comparative risk assessment. FINDINGS: In 2019, there were 3·94 million (95% uncertainty interval 3·43-4·58) new stroke cases in China. The incidence rate of stroke increased by 86·0% (73·2-99·0) from 1990, reaching 276·7 (241·3-322·0) per 100 000 population in 2019. The age-standardised incidence rate declined by 9·3% (3·3-15·5) from 1990 to 2019. Among 28·76 million (25·60-32·21) prevalent cases of stroke in 2019, 24·18 million (20·80-27·87) were ischaemic stroke, 4·36 million (3·69-5·05) were intracerebral haemorrhage, and 1·58 million (1·32-1·91) were subarachnoid haemorrhage. The prevalence rate increased by 106·0% (93·7-118·8) and age-standardised prevalence rate increased by 13·2% (7·7-19·1) from 1990 to 2019. In 2019, there were 2·19 million (1·89-2·51) deaths and 45·9 million (39·8-52·3) DALYs due to stroke. The mortality rate increased by 32·3% (8·6-59·0) from 1990 to 2019. Over the same period, the age-standardised mortality rate decreased by 39·8% (28·6-50·7) and the DALY rate decreased by 41·6% (30·7-50·9). High systolic blood pressure, ambient particulate matter pollution exposure, smoking, and diet high in sodium were four major risk factors for stroke burden in 2019. Moreover, we found marked differences of stroke burden and attributable risk factors across provinces in China from 1990 to 2019. INTERPRETATION: The disease burden of stroke is still severe in China, although the age-standardised incidence and mortality rates have decreased since 1990. The stroke burden in China might be reduced through blood pressure management, lifestyle interventions, and air pollution control. Moreover, because substantial heterogeneity of stroke burden existed in different provinces, improved health care is needed in provinces with heavy stroke burden. FUNDING: National Key Research and Development Program of China and Taikang Yicai Public Health and Epidemic Control Fund.

Decreased expression of fibroblast growth factor 13 in early-onset preeclampsia is associated with the increased trophoblast permeability.

OBJECTIVE: Intracellular protein fibroblast growth factor 13 (FGF13) is highly expressed in human placenta, although its biological function remains unexplored. The aims of this study were to investigate the expression of FGF13 in placentae with early-onset preeclampsia (PE) and the associated mechanisms in the pathophysiology of PE. METHODS: The expression levels of FGF13 in placentae obtained from patients with early-onset PE and normal pregnancies were assessed using immunofluorescent staining, Western blot assays and quantitative PCR. We knocked down FGF13 in trophoblast cell lines BeWo and HTR8/SVneo, and analyzed cell permeability. Clinical trophoblast cell-cell junctions were identified by cytokeratin 7 (CK7) immunofluorescent staining of human placental sections. The expressions of FGF13 were manipulated in BeWo and HTR8/SVneo cell lines, and the expressions of E-cadherin were quantified by reverse transcription followed by quantitative PCR, Western blot assays and immunofluorescent staining. The expressions of FGF13 and E-cadherin were further confirmed in the isolated human primary trophoblasts. RESULTS: Downregulation of FGF13 along with trophoblast disarrangement were found in human placentae with early-onset PE. In trophoblast cell lines decreased FGF13 expression resulted in increased cell permeability and decreased E-cadherin expression. The FGF13 insufficiency-mediated loss of E-cadherin was further confirmed in the human villous trophoblasts isolated from PE patients. CONCLUSION: FGF13 was downregulated in human placentae with early-onset PE. FGF13 played an important role in maintaining placental trophoblast permeability via the modulation of E-cadherin.