Impact of hyperglycaemia on complications in patients who had a stroke after thrombolysis.

BACKGROUND: We sought to investigate whether admission hyperglycaemia is associated with complications in patients who had an acute ischaemic stroke (AIS) treated with intravenous recombinant tissue plasminogen activator and, if so, whether complications during hospitalisation modify the effect of hyperglycaemia on 3-month poor outcome after thrombolysis. METHODS: Patients who were diagnosed with AIS after thrombolysis between July 2016 and January 2019 were enrolled in this study. Five prespecified complications, including infections, brain oedema, deep vein thrombosis (DVT), haemorrhagic transformation (HT) and gastrointestinal bleeding, were recorded during hospitalisation. RESULTS: Of 388 patients, 143 (36.86%) presented with hyperglycaemia. Patients with hyperglycaemia were more likely to experience one or more complications than patients without hyperglycaemia. After adjustment for potential confounders, hyperglycaemia was associated with brain oedema (OR 2.39; 95% CI 1.08 to 5.30), HT (OR 2.16, 95% CI 1.06 to 4.41), symptomatic intracerebral haemorrhage (sICH) (OR 7.32, 95% CI 2.35 to 22.80) and gastrointestinal bleeding (OR 3.62; 95% CI 1.93 to 6.80), but was not linked to infections (OR 1.48, 95% CI 0.76 to 2.9) and DVT (OR 0.60, 95% CI 0.23 to 1.5). Additional adjustment for the complications in the clinical outcome analysis, done to assess these complications as an intermediate in the pathway from admission hyperglycaemia to clinical outcome, did not substantially change the model (all p for interaction >0.05). CONCLUSION: Hyperglycaemia is an independent predictor of complications following stroke after thrombolysis, especially for brain oedema, gastrointestinal bleeding, HT and sICH. Complications during hospitalisation did not modify the effect of hyperglycaemia on the poor outcome at 3 months in ischaemic stroke.

Dynamic increase in neutrophil levels predicts parenchymal hemorrhage and function outcome of ischemic stroke with r-tPA thrombolysis.

BACKGROUND: The higher level of neutrophil on admission has been reported to predict worse 3-month outcomes in ischemic stroke patients. Our study was to explore the dynamic changes of neutrophil and lymphocyte after r-tPA thrombolysis of ischemic stroke and the relationship with parenchymal hemorrhage (PH) and 3-month function outcome. METHODS: A total of 208 acute ischemic stroke (AIS) patients with intravenous thrombolysis were included and then received 3-month follow-up in the present study. Blood samples for neutrophil and lymphocyte counts were obtained on admission, at 24 h and at 7 days after r-tPA infusion. The associations of increase in neutrophil, lymphocyte, and neutrophil to lymphocyte ratio (NLR) with PH or 3-month poor outcome were examined by logistic regression. RESULTS: Increasing trends in the neutrophil and NLR were observed in AIS patients after r-tPA treatment. Increased level of neutrophil at 24 h after r-tPA infusion but not that on admission was associated with PH (OR = 2.86, P = 0.029) and 3-month poorer functional outcomes (OR = 2.67, P = 0.009). Moreover, patients were divided into four groups according to the percent change in neutrophil within 24 h following r-tPA treatment, and we found that there was a trend of incremental OR when compared higher increase group with lower ones. CONCLUSIONS: Dynamic increase in neutrophil and NLR after stroke may predict PH and 3-month poor outcome in AIS patients receiving r-tPA treatment. Therefore, neutrophil and NLR may serve as activity markers for PH and 3-month poor prognosis in AIS patients with intravenous thrombolysis.

Soluble lectin-like oxidized low-density lipoprotein receptor-1 as a novel biomarker for large-artery atherosclerotic stroke.

BACKGROUND: Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been shown associated with the progression of atherosclerosis in endothelial cells. We sought to assess whether the baseline serum sLOX-1 levels are correlated with the presence and short-term functional outcome of large-artery atherosclerotic (LAA) stroke. METHODS: The study recruited 241 subjects, including 148 consecutive patients with acute ischemic stroke with the subtype of LAA and 93 non-stroke controls. Clinical and laboratory data, including serum concentration of sLOX-1, were collected within 24 h of admission, and the severity of LAA stroke patients was evaluated by National Institutes of Health Stroke Scale score. And functional outcome was assessed by modified Rankin Scale three months after stroke. The association between sLOX-1 level and the functional outcome at three months was analyzed by multiple logistic regression models. RESULTS: Serum levels of sLOX-1 in the LAA stroke patients were significantly higher as compared to normal controls (2.48 ± 0.93 ng/ml vs. 2.22 ± 0.79 ng/ml in the controls, t = 2.301, p = 0.022). The levels of serum sLOX-1 in patients with good outcome were significantly lower than those with poor outcome (2.39 ± 0.94 ng/ml vs. 2.77 ± 0.84 ng/ml, p = 0.032). After adjusting for potential confounders, sLOX-1 was still an independent predictor for the function outcome with an adjusted OR of 3.39 (95% CI, 1.61-7.11, p = 0.001). CONCLUSIONS: The serum sLOX-1 level was higher in patients with LAA stroke, and it was an independent predictor of functional outcome in patients with LAA ischemic stroke.

Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres.

Early neovascularization is important for autologous fat transplant survival. SVF cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and SVF cells can promote neovascularization. However, the half-life (about 50 min) of VEGF is too short to sustain an adequate local concentration. We have investigated whether VEGF-polylactic acid (PLA) nano-sustained release microspheres plus SVF cells can improve neovascularization and survival of transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano-sustained release microspheres in vitro. Human fat tissues was mixed with SVF cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the control. These three mixtures were injected into random sites in 18 nude mice. Two months later, the transplants were weighed and examined histologically; and capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE) and anti-VEGF stains were applied to reveal cell infiltration. The mean wet weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were 0.18 ± 0.013 g, 0.16 ± 0.015 g, and 0.071 ± 0.12 g, respectively; the differences between groups were statistically significant. More vessels were present in the SVF plus VEGF-PLA transplants than in the other two types. Transplants mixed with SVF cells also had an acceptable density of capillaries. Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone transplants, but not the control transplants, were composed of adipose tissue, and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF-PLA transplants had significantly greater capillary density and VEGF expression than the other two transplant groups. Thus transplanted fat tissue survival and quality can be enhanced by the addition of VEGF-PLA nano-sustained release microspheres plus SVF cells.

Maternal high fat diet programs spatial learning and central leptin signaling in mouse offspring in a sex-specific manner.

Environmental factors in early life have been demonstrated to increase the risk of neurodevelopmental disorders in offspring, especially the deficiency of the cognitive ability. Leptin has emerged as a key hormone that conveys information on energy stores, but there is growing appreciation that leptin signaling may also play an important role in neurodevelopment. The present study aimed to investigate whether maternal HFD exposure impairs the offspring learning and memory through the programming of central leptin system. We observed that hippocampus-dependent learning and memory were impaired in male but not female offspring from HFD-fed maternal ancestors (C57BL/6 mice), as assessed by novel object recognition and Morris water maze tests. Moreover, the chromatin immunoprecipitation results revealed the maternal HFD consumption led to the increasement in the binding of the histone marker H3K9me3 in male offspring, which mediates gene silencing in the leptin receptor promoter region. Furthermore, there was an increase in the expression of the histone methylase SUV39H1 in male but not female offspring, which regulates H3K9me3. Additionally, it has been observed that IL-6 and IL-1 also could lead to similar alternations when acting on cultured hippocampal neurons in vitro. Taken together, our data suggest that maternal HFD consumption influences male offspring hippocampal cognitive performance in a sex-specific manner, and central leptin signaling may serve as the cross-talk between maternal diet and cognitive impairment in offspring.

Maternal High-Fat Diet Multigenerationally Programs HPA Function and Behaviors in Male Rat Offspring.

Maternal environmental factors have been demonstrated to exert significant influences on the health of offspring. The hypothalamic-pituitary-adrenal (HPA) axis is an important neuroendocrine stress system that can be influenced by early life challenges. Our previous research has revealed that the consumption of a high-fat diet (HFD) by pregnant and lactating rats leads to the programming of HPA axis activity in male offspring of the first generation (referred to as F1HFD/C). The present study aimed to investigate whether the observed remodeling of the HPA axis could be inherited by second-generation male offspring (referred to as F2HFD/C), following maternal HFD exposure. The results showed that F2HFD/C rats exhibited enhanced basal HPA axis activity, similar to their F1HFD/C ancestors. Moreover, F2HFD/C rats displayed exacerbated corticosterone responses to restraint and lipopolysaccharide-induced stress, but not to insulin-induced hypoglycemia stress. Furthermore, maternal HFD exposure significantly aggravated depression-like behavior in the F2 generation subjected to chronic unpredictable mild stress. To investigate the role of central calcitonin gene-related peptide (CGRP) signaling in maternal diet-induced programming of the HPA axis across generations, we conducted central infusion of αCGRP8-37, a CGRP receptor antagonist, in F2HFD/C rats. The results demonstrated that αCGRP8-37 attenuated depression-like behaviors and reduced the hyperresponsiveness of the HPA axis to restraint stress in these rats. Therefore, central CGRP signaling may contribute to maternal diet-induced programming of HPA axis across generations. In conclusion, our study provides evidence that maternal HFD consumption can lead to multigenerational programming of the HPA axis and behaviors in adult male descendants.

Genetic diversity and variance of Stentor coeruleus (Ciliophora: Heterotrichea) inferred from inter-simple sequence repeat (ISSR) fingerprinting.

We used inter-simple sequence repeat fingerprinting to analyze the genetic structure of 16 populations of Stentor coeruleus from three lakes and three ponds in China. Using 14 polymorphic primers, a total of 99 discernible DNA fragments were detected, among which 76 (76.77%) were polymorphic, indicating median genetic diversity in these populations. Further, both Nei's gene diversity (h) and Shannon's information index (I) between the different populations revealed a median genetic diversity. At the same time, gene flow was interpreted to be low. The main factors responsible for the median level of diversity and low gene flow within populations are probably due to a low frequency of sexual recombinations. Analysis of molecular variance showed that there was high genetic differentiation among the five water bodies. Both cluster analysis and a nonmetric multidimensional scaling analysis suggested that genotypes isolated from the same locations displayed a higher genetic similarity than those from different ones, separating populations into subgroups according to their geographical locations. However, there is a weak positive correlation between the genetic distance and geographical distance.

2-BFI attenuates ischemic injury by modulating mTOR signaling and neuroinflammation in rats.

Ischemic stroke is one of the major diseases that cause mortality and morbidity of human beings, but there is still lack of effective treatment and prevention. We found that 2-(2-Benzofuranyl)-2-Imidazoline (2-BFI) is potently protective against stroke and acute inflammatory immune disease. Moreover, the mammalian target of rapamycin (mTOR) signaling contributes effectively to the modulation of post-stroke neuroinflammatory response. However, whether the protection of 2-BFI against ischemic injury is through mTOR-mediated neuroinflammatory response remains unestablished. Here, we used 2-BFI to treat ischemic rats induced by distal middle cerebral artery occlusion (dMCAO). We found that 2-BFI administration after dMCAO improved the neurological deficits and decreased the infarct volume. 2-BFI reduced phosphorylation of mTOR and p70S6, increased IL-10 and TGF-ß, and decreased IFN-γ levels in ischemic rats. Our results demonstrated that 2-BFI attenuates ischemic injury by inhibiting the activation of mTOR signaling and modulating neuroinflammation after stroke in rats.

Maternal High-Fat Diet Multigenerationally Impairs Hippocampal Synaptic Plasticity and Memory in Male Rat Offspring.

As advances are made in the field of developmental origins of health and disease, there is an emphasis on long-term influence of maternal environmental factors on offspring health. Maternal high-fat diet (HFD) consumption has been suggested to exert detrimental effects on cognitive function in offspring, but whether HFD-dependent brain remodeling can be transmitted to the next generations is still unclear. This study tested the hypothesis that HFD consumption during rat pregnancy and lactation multigenerationally influences male offspring hippocampal synaptic plasticity and cognitive function. We observed that hippocampus-dependent learning and memory was impaired in 3 generations from HFD-fed maternal ancestors (referred as F1-F3), as assessed by novel object recognition and Morris water maze tests. Moreover, maternal HFD exposure also affected electrophysiological and ultrastructure measures of hippocampal synaptic plasticity across generations. We observed that intranasal insulin replacement partially rescued hippocampal synaptic plasticity and cognitive deficits in F3 rats, suggesting central insulin resistance may play an important role in maternal diet-induced neuroplasticity impairment. Furthermore, maternal HFD exposure enhanced the palmitoylation of GluA1 critically involved in long-term potentiation induction, while palmitoylation inhibitor 2-bromopalmitate counteracts GluA1 hyperpalmitoylation and partially abolishes the detrimental effects of maternal diet on learning and memory in F3 offspring. Importantly, maternal HFD-dependent GluA1 hyperpalmitoylation was reversed by insulin replacement. Taken together, our data suggest that maternal HFD exposure multigenerationally influences adult male offspring hippocampal synaptic plasticity and cognitive performance, and central insulin resistance may serve as the cross-talk between maternal diet and cognitive impairment across generations.

Neutrophil-to-lymphocyte ratio, hyperglycemia, and outcomes in ischemic stroke patients treated with intravenous thrombolysis.

INTRODUCTION: Increased neutrophil-to-lymphocyte ratio (NLR) and hyperglycemia on admission are associated with poor outcomes in acute ischemic stroke (AIS) patients. We sought to evaluate the combined effect of increased NLR and hyperglycemia on the prognosis of ischemia stroke treated with intravenous thrombolysis (IVT). METHODS: Patients with acute ischemic stroke receiving IVT treatment were prospectively enrolled. All participants were followed for 3 months. According to the levels of NLR and blood glucose, patients were categorized into four groups: high NLR or nonhigh NLR with or without hyperglycemia. The associations between NLR values with or without hyperglycemia and outcomes of stroke after thrombolysis were assessed by multivariable logistic regression analysis. RESULTS: Among the 381 stroke patients (median age 68 years, 61.68% man) included, 155 (40.68%) had a poor outcome (modified Rankin Scale score 3-6) during 3 months. After multivariate adjustment, high NLR with hyperglycemia increased the risk of 3-month poor outcome (OR = 4.42; 95% CI, 2.13-9.16), early neurological deterioration (END) (OR = 4.81; 95% CI, 2.08-11.12), and 3-month mortality (OR = 6.56; 95% CI, 1.92-22.40). A significant multiplicative interaction of NLR and blood glucose on 3-month poor outcome in ischemic stroke patients after thrombolysis was observed. CONCLUSIONS: Ischemic stroke patients with concurrent high NLR and hyperglycemia increased risks of END, 3-month poor outcome, and mortality after thrombolysis.

Mean Platelet Volume-To-Lymphocyte Ratio Predicts Poor Functional Outcomes Among Ischemic Stroke Patients Treated With Intravenous Thrombolysis.

Background and Purpose: According to previous studies, the mean platelet volume-to-lymphocyte ratio (MPVLR) represents a novel marker of a poor short-term prognosis in patients with a myocardial infarction who underwent primary percutaneous coronary intervention. We aimed to evaluate the association between MPVLR and clinical outcomes of patients with acute ischemic stroke who were treated with intravenous thrombolysis. Methods: Two hundred forty-one patients with ischemic stroke receiving intravenous thrombolysis were prospectively enrolled in this study. Blood samples for MPVLR were obtained at admission and at 18-24 h after treatment with intravenous thrombolysis. A poor functional outcome was defined as a modified Rankin scale score of 3-6 at 3 months after stroke. Results: At admission, the area under the curve of MPVLR to predict poor functional outcomes at 3 months was 0.613 [95% confidence interval (CI), 0.541-0.686; P = 0.003), and the best predictive MPVLR value was 5.8. Patients with an MPVLR ≥5.8 had a 3.141-fold increased risk of a poor outcome at 3 months (95% CI, 1.491-6.615; P = 0.003) compared to patients with an MPVLR <5.8. At 18-24 h after treatment with intravenous thrombolysis, the area under the curve of MPVLR to predict a poor outcome at 3 months was 0.697 (95% CI, 0.630-0.765, P < 0.001), and the best predictive MPVLR value was 6.9. The inclusion of MPVLR as a continuous (odds ratio, 1.145; 95% CI, 1.044-1.256, P = 0.004) and categorical variable (odds ratio, 6.555; 95% CI, 2.986-14.393, P < 0.001) was independently associated with poor outcomes at 3 months. Conclusions: Both the values of MPVLR at admission and 18-24 h after intravenous thrombolysis were independently associated with poor functional outcomes. MPVLR may serve as an activity marker for a poor prognosis in patients with acute ischemic stroke receiving intravenous thrombolysis.

Maternal high fat diet programs hypothalamic-pituitary-adrenal function in adult rat offspring.

Maternal environmental factors such as diet have profound effects on offspring development and later health. The hypothalamic-pituitary-adrenal (HPA) axis is an important stress neuroendocrine system that is subject to programming by early life challenges. The present study was further to investigate whether maternal high fat diet (HFD) exposure during rat pregnancy and lactation can alter the HPA axis activity in adult male offspring. We observed that maternal HFD consumption exerted long-term effects on the basal activity of the HPA axis in adult offspring, with increased mean plasma corticosterone levels that result from elevated steroid pulse frequence and pulse amplitude. More importantly, maternal HFD offspring displayed enhanced corticosterone responses to restraint (1 h) and lipopolysaccharide (25 µg/kg, iv) but not insulin-induced hypoglycemia (0.3U/kg, iv) stress, suggesting a stressor-specific effect of maternal diet on the hyperresponsiveness of the HPA axis to stress. Additionally, maternal HFD exposure markedly attenuated the habituation of HPA responses to repeated restraint stress. These findings demonstrate that perinatal HFD exposure has a potent and long-lasting influence on development of neuroendocrine regulatory mechanisms. Maternal HFD consumption significantly increased basal corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus; nevertheless, similar increments in CRF mRNA levels following restraint were observed between maternal HFD offspring and control rats. Furthermore, the medial and central nuclei of amygdala played a pivotal role in maternal HFD-induced sensitization of the HPA response to psychological and systemic stress, respectively, suggesting that different neural pathways may mediate maternal HFD-induced HPA hyperresponsivity to different types of stressors. Take together, the long-term effects of maternal HFD challenge on the central regulation of the HPA axis, therefore, expose the adult offspring to greater HPA function throughout lifespan, in stressor-specific and region-specific manner.

Biogeographic patterns of abundant and rare bacterioplankton in three subtropical bays resulting from selective and neutral processes.

Unraveling the relative importance of ecological processes regulating microbial community structure is a central goal in microbial ecology. Here, we used high-throughput sequencing to examine the relative contribution of selective and neutral processes in the assembly of abundant and rare subcommunities from three subtropical bays of China. We found that abundant and rare bacterial taxa were distinctly different in diversity, despite the similar biogeographic patterns and strong distance-decay relationships, but the dispersal of rare bacterial taxa was more limited than that of abundant taxa. Furthermore, the environmental (selective processes) and spatial (neutral processes) factors seemed to govern the assembly and biogeography of abundant and rare bacterial subcommunities, although both factors explained only a small fraction of variation within the rare subcommunity. More importantly, variation partitioning (based on adjusted R2 in redundancy analysis) showed that spatial factors exhibited a slightly greater influence on both abundant and rare subcommunities compared to environmental selection; however, the abundant subcommunity had a much stronger response to spatial factors (17.3% of pure variance was explained) than that shown by the rare bacteria (3.5%). These results demonstrate that environmental selection and neutral processes explained the similar biogeographic patterns of abundant and rare subcommunities, but a large proportion of unexplained variation in the rare taxa (91.1%) implies that more complex assembly mechanisms may exist to shape the rare bacterial assemblages in the three subtropical bays.

Maternal high-fat diet programs cerebrovascular remodeling in adult rat offspring.

Maternal environmental factors such as diet have consequences on later health of the offspring. We found that maternal high-fat diet (HFD) exposure renders adult offspring brain more susceptible to ischemic injury. The present study was further to investigate whether HFD consumption during rat pregnancy and lactation influences the cerebral vasculature in adult male offspring. Besides the endothelial damage observed in the transmission electron microscopy, the MCAs of offspring from fat-fed dams fed with control diet (HFD/C) also displayed increased wall thickness and media/lumen ratio, suggesting that cerebrovascular hypertrophy or hyperplasia occurs. Moreover, smaller lumen diameter and elevated myogenic tone of the MCAs over a range of intralumenal pressures indicate inward cerebrovascular remodeling in HFD/C rats, with a concomitant increase in vessel stiffness. More importantly, both wire and pressure myography demonstrated that maternal HFD intake also enhanced the MCAs contractility to ET-1, accompanied by increases in ET types A receptor (ETAR) but not B (ETBR) density in the arteries. Furthermore, ETAR antagonism but not ETBR antagonism restored maternal HFD-induced cerebrovascular dysfunction in adult offspring. Taken together, maternal diet can substantially influence adult offspring cerebrovascular health, through remodeling of both structure and function, at least partially in an ET-1 manner.

DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy.

Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95-nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95-nNOS interactions in MHE.

Prognostic value of serum thioredoxin levels in ischemic stroke.

OBJECTIVES: Thioredoxin (Trx) is one of significant antioxidative molecules to diminish oxidative stress. Current evidence suggests that Trx is a potent antioxidant with cytoprotective functions. The aim of our study was to investigate specifically the association between serum Trx levels and acute ischemic stroke (AIS) patients. METHODS: 198 AIS patients and 75 controls were enrolled to the study. Serum Trx levels were measured using an enzyme-linked immunosorbent assay (ELISA). Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS) score on admission. Clinical endpoint was functional outcome measured by Barthel Index (BI) 3 months after admission. Multivariate binary logistic regression analyses were performed to identify predictors. RESULTS: We found that serum Trx levels were significantly increased in patients as compared to controls. Serum Trx was an independent biomarker to predict ischemic stroke (OR, 1.264; 95% CI, 1.04-1.537; P = 0.019). In addition, there was a negative correlation between NIHSS score at admission and serum Trx levels in cardioembolic stroke patients (r = -0.422; P = 0.013). Furthermore, higher serum Trx levels in AIS patients were associated with favorable functional outcome. Serum Trx was an independent predictor for the functional outcome (OR, 0.862; 95% CI, 0.75-0.991; P = 0.037). CONCLUSIONS: Serum Trx might be as a biomarker of cardioembolic stroke severity. Increased serum Trx levels could be a useful tool to predict good prognosis in patients with AIS.

Left atrial size and risk of recurrent ischemic stroke in a Chinese population.

BACKGROUND: Although a number of studies have reported the role of an increased left atrial (LA) size on stroke, limited data are collected about the relationship between LA enlargement and recurrent ischemic stroke in the Chinese population. Our aim was to assess the association of LA size with the risk of stroke recurrence, particularly with recurrent cardioembolic or cryptogenic stroke in ischemic stroke patients. METHODS: The study recruited 313 consecutive patients with acute first-ever ischemic stroke. Echocardiographic LA diameter was measured and indexed by height and body surface area separately. The endpoint was recurrent ischemic stroke. Cox proportional hazard models were used to examine the association of LA size with total recurrent ischemic stroke and recurrent cardioembolic or cryptogenic stroke while adjusting for baseline demographics characteristics, clinical factors, echocardiographic left ventricular ejection fraction, and medication. RESULTS: Over a median follow-up period of 1.63 years, 47 recurrent ischemic strokes (21 were cardioembolic or cryptogenic) occurred. In a multivariate model adjusted for potential confounders, compared with the bottom tertiles of LA diameter indexed to height (LA diameter/H), the top tertile of LA diameter/H was significantly associated with the total recurrent ischemic stroke (adjusted HR 3.610, 95% CI 1.870-6.967, p < .001) and the composite of recurrent cardioembolic or cryptogenic stroke (adjusted HR 5.673, 95% CI 1.780-18.084, p = .003). Results were similar when LA diameter indexed to body surface area (LA diameter/BSA) was involved in the analysis. CONCLUSION: LA size is an independent predictor of total recurrent ischemic stroke and the composite of recurrent cardioembolic or cryptogenic stroke.

Bulbocavernosus Reflex Test for Diagnosis of Pudendal Nerve Injury in Female Patients with Diabetic Neurogenic Bladder.

The study was designed to investigate the clinical application and significance of the bulbocavernosus reflex (BCR) test for diagnosing diabetic neurogenic bladder (DNB) in female subjects. In this study, 68 female patients with DNB and 40 female normal controls were subjected to a nerve conduction study (NCS) of all four limbs and the BCR test. The data were analyzed and compared, and the corresponding diagnostic sensitivities were discussed. Mean BCR latency for female DNB patients was significantly prolonged, compared to that of the control group, suggesting pudendal nerve injuries in female DNB patients. Moreover, DNB patients were categorized according to the diabetes course. Compared to that of Group A (diabetes course < 5 y), the mean BCR latency was significantly prolonged in Group B (diabetes course between 5 and 10 y) and then further prolonged in Group C (diabetes course > 10 y), which were all longer than the control group. Furthermore, compared with that of the controls, the mean BCR latency was prolonged in DNB patients with or without NCS abnormalities in limbs. Nevertheless, no significant difference was observed in BCR latency between DNB patients with and without NCS abnormalities. Significantly increasing trends were also observed in the NCS and BCR abnormality rates along with increased diabetes course. Most importantly, compared with the NCS of limbs, the BCR test was more sensitive in diagnosing DNB in the female subjects. Overall, our findings suggest that the BCR test would help to assess the pudendal nerve injury in female DNB patients, which might be a potential diagnostic tool in the clinic.

Maternal high-fat diet influences stroke outcome in adult rat offspring.

Diet-induced epigenetic modifications in early life could contribute to later health problem. However, it remains to be established whether high-fat diet (HFD) consumption during pregnancy and the suckling period could predispose the offspring to stroke. The present study investigated the influence of maternal HFD on stroke outcome in adult offspring. Female Sprague-Dawley rats were fed a normal diet (5.3% fat) or a HFD (25.7% fat), just before pregnancy until the end of lactation. Male offspring were fed with the control diet or the HFD after weaning, to form four groups (control offspring fed with the control diet (C/C) or the HFD (C/HFD) and offspring of fat-fed dams fed with the control diet (HFD/C) or the HFD (HFD/HFD)). The offspring received middle cerebral artery occlusion on day 120 followed by behavioral tests (neurological deficit score, staircase-reaching test and beam-traversing test), and infarct volumes were also calculated. We found that the HFD/C rats displayed larger infarct volume and aggravated functional deficits (all P<0.05), compared with the C/C rats, indicating that maternal fat-rich diet renders the brain more susceptible to the consequences of ischemic injury. Moreover, maternal HFD offspring displayed elevated glucocorticoid concentrations following stroke, and increased glucocorticoid receptor expression. In addition, adrenalectomy reversed the effects of maternal HFD on stroke outcome when corticosterone was replaced at baseline, but not ischemic, concentrations. Furthermore, expression of brain-derived neurotrophic factor (BDNF) in the ipsilateral hippocampus was decreased in the HFD/C offspring (P<0.05), compared with the C/C offspring. Taken together, maternal diet can substantially influence adult cerebrovascular health, through the programming of central BDNF expression and the hypothalamic-pituitary-adrenal axis.

Estrogen therapy increases BDNF expression and improves post-stroke depression in ovariectomy-treated rats.

The present study investigated the effect of exogenous estrogen on post-stroke depression. Rats were exposed to chronic mild stress following middle cerebral artery occlusion. The occurrence of post-stroke depression was evaluated according to the changes in preference for sucrose and performance in a forced swimming test. Estrogen therapy significantly improved these neurological symptoms, indicating that estrogen is effective in treating post-stroke depression. Increased brain-derived neurotrophic factor (BDNF) expression was reported in the hippocampus of rats that had been treated with estrogen for two weeks, suggesting that BDNF expression may be an important contributor to the improvement of post-stroke depression that is observed following estrogen therapy.