Intramyocardial Hemorrhage Leads to Higher MACE Rate by Increasing Myocardial Infarction Volume in Patients with STEMI.

Background and Aims: Whether IMH can directly cause persistent myocardial necrosis after reperfusion therapy in STEMI patients is still unclear. We conducted a prospective study to compare the cardiovascular parameters in patients with STEMI with and without IMH to explore the potential correlations between IMH and poor outcomes. Methods and Results: We prospectively enrolled 65 consecutive patients with newly diagnosed STEMI admitted to the CCU of the Second Xiangya Hospital of Central South University between April 2019 and November 2021, all of whom underwent primary PCI. Of these, 38 (58.5%) and 27 (41.5%) patients were in the IMH-absent and IMH-present groups, respectively. At a mean time of 5-7 days after reperfusion therapy, the volume of MI measured using LGE sequence was larger in STEMI patients with IMH than in patients without IMH (34.2 ± 12.7 cm3 vs 21.1 ± 13.1 cm3, P<0.001). HsTNT levels were significantly higher in the IMH-present group than in the IMH-absent [2500.0 (1681.5-4307.0) pg/mL vs 1710.0 (203.0-3363.5) pg/mL, P=0.021] group during hospitalization. The LVEF measured using CMR in the IMH-present group was lower than that in the IMH-absent group (30.7 ± 9.8% vs 42.3 ± 11.0%, P < 0.001). The rate of MACE at 12 months in IMH-present group was significantly higher than in the IMH-absent group (9/27 VS 2/38, P = 0.012). Conclusion: IMH can lead to further expansion of MI volumes in patients with STEMI, resulting in lower LVEF and higher MACE rate in the post-discharge follow-up.

Functional Outcome and Mortality Predictors in Patients with Cerebral Ischemic Infarction After Decompressive Craniectomy: Cross-Sectional Study.

OBJECTIVE: Surgeons commonly perform Decompressive craniectomy (DC) to manage patients with cerebral ischemic infarction. However, there are conflicting data on the long-term functional outcomes following DC. Therefore, this study aims to determine the functional outcome of patients with cerebral ischemic infarction after DC. METHODS: This prospective and retrospective cross-sectional study included 148 patients with cerebral ischemic infarction who underwent DC at Ghaem Hospital, Mashhad, Iran, from March 2011 to March 2021. The Modified Rankin Scale (mRS) assesses disability in these patients and determines the recovery and degree of long-term functional outcomes. Demographic and clinical data were extracted and recorded in a researcher-made questionnaire. RESULTS: In summary, the follow-up revealed a survival rate of 39.2% among patients with ischemic stroke. The comparison of the mean infarct volume in patients with various mRS scores showed that the mean infarct volume was significantly higher in patients with unfavorable functional outcomes, based on mRS scores at discharge (P = 0.05), 3 months mRS (P < 0.01), and mRS score at final follow-up (P = 0.01). Final mortality was higher in patients with higher mRS scores at discharge, after 3 months, and final follow-up (P < 0.01). Older age and infarction volume can predict mRS and mortality in patients with ischemic stroke (P < 0.01). CONCLUSIONS: The present study showed that mortality and mRS scores at various times are associated with infarction volume and older age in patients with ischemic stroke.

Massive Neonatal Arterial Ischemic Stroke.

BACKGROUND: Massive infarction in adults is a devastating entity characterized by signs of extreme swelling of the brain's parenchyma. We explored whether a similar entity exists in neonates, which we call massive neonatal arterial ischemic stroke (M-NAIS), and assess its potential clinical implications. METHODS: Prospective multicenter cohort study comprising 48 neonates with gestational age ≥35 weeks with middle cerebral artery (MCA) NAIS was performed. Diagnosis with magnetic resonance imaging (MRI) was performed within the first three days after symptom onset. The presence of signs of a space-occupying mass, such as brain midline shift and/or ventricular and/or extra-axial space collapse, was recorded. The volume of the infarct and brain midline shift were determined with semiautomatic procedures. Neurodevelopment was assessed at age 24 months. RESULTS: Fifteen (31%) neonates presented MRI signs of a space-occupying mass effect and were considered to have an M-NAIS. The relative volume (infarct volume/total brain volume) of the infarct was on average significantly greater in the M-NAIS subgroup (29% vs 4.9%, P < 0.001). Patients with M-NAIS consistently presented lesions involving the M1 arterial territory of the MCA and showed more apneic and tonic seizures, which had an earlier onset and lasted longer. Moderate to severe adverse neurodevelopmental outcomes were present in most M-NAIS cases (79% vs 6%, P < 0.001). CONCLUSIONS: M-NAIS appears to be a distinctive subtype of neonatal infarction, defined by characteristic neuroimaging signs. Neonates with M-NAIS frequently present a moderate to severe adverse outcome. Early M-NAIS identification would allow for prompt, specific rehabilitation interventions and would provide more accurate prognostic information to families.

Association of inferior division MCA stroke location with populations with atrial fibrillation incidence.

BACKGROUND AND AIM: Considering the anatomical features of Middle Cerebral Artery (MCA) bifurcation, larger emboli are more likely to enter the inferior division over the superior division. Since emboli of cardiac origin are larger on average than emboli of arterial origin, we hypothesize that the infarcts in temporal and parietal lobes are more likely associated to atrial fibrillation than those in the frontal lobes, therefore occurring more often in populations with higher incidence of atrial fibrillation, such as male (compared to women) and white (compared to black) patients. METHODS: We included 197 patients with MCA "temporoparietal predominant" infarcts and 105 with "frontal predominant" infarcts. Variations between stroke location (frontal or temporoparietal), sex, and race were examined via Chi-square test. RESULTS: Male patients were more likely than female patients to be afflicted by temporoparietal strokes versus frontal strokes, while white patients had greater likelihood than black patients to be afflicted by temporoparietal strokes versus frontal strokes. Patients with confirmed diagnosis of atrial fibrillation display more temporoparietal strokes compared to frontal strokes. CONCLUSION: Temporoparietal MCA ischemic strokes occur more frequently in male and white patients: populations with known increased incidence of atrial fibrillation. In addition, population-specific anatomical characteristics of the MCA bifurcation might favor the larger cardiac emboli to enter the inferior division and cause temporoparietal infarcts. This association can help guide search for the most likely etiology of infarcts.

Evaluating blood-brain barrier disruption and infarction volume concurrently in rats subjected to ischemic stroke using an optical imaging system.

BACKGROUND: Blood-brain barrier (BBB) disruption is pivotal in the pathophysiological process of ischemic stroke and is often measured in rodent stroke studies. Traditionally, rodent BBB permeability increase is determined by measuring cerebral leakage of certain dyes such as Evans Blue or sodium fluorescein (NaFL). However, due to the special processing of samples for BBB permeability measurement, they cannot be used afterward for determining other essential parameters such as cerebral infarction volume. Therefore, using different batches of animals for assessing BBB permeability and infarction volume is typical. However, this would limit the stroke study's statistical power and scientific value while hindering the implementation of procedures for high standard animal welfare. NEW METHOD: The rats subjected to middle cerebral artery occlusion (MCAO) were intraperitoneally injected with NaFL during the reperfusion phase. The brains were sliced and measured for BBB permeability using the small animal optical imaging system (IVIS® Lumia series III). Afterward, the same brain samples were either sliced or homogenized for tests that assessed infarction volume or other molecular changes. RESULTS: The sum fluorescence intensity of the ischemic brain slices under the IVIS® Lumia series Ⅲ showed a strong correlation with the infarction volume determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining (r = 0.7440, P = 0.0087). The fluorescence intensity of the whole ischemic brain was correlated with the NaFL concentration of brain tissue homogenates (r = 0.8653, P = 0.0026) and cerebral infarction volume (r = 0.7282, P = 0.0072). COMPARISON WITH EXISTING METHODS: The new method enables concurrent measurement of BBB permeability and infarction volume on the same batch of brain tissue samples without affecting most downstream biochemical assays. CONCLUSIONS: By applying the new method, we could use the same batch of ischemic rodent brain tissue for multiple assays, including BBB permeability and infarction volume. Through this, we would reduce the animal numbers in each study and help to maximize the scientific and statistical potential of future rodent ischemic studies.

Alleviative effects of foraging exercise on depressive-like behaviors in chronic mild stress-induced ischemic rat model.

BACKGROUND: Poststroke depression (PSD) is a common complication that seriously affects the functional recovery and prognosis of an individual. As some patients with PSD fail to respond to drug therapy, it is urgent to find a viable alternative treatment. METHODS: An active exercise program known as foraging exercise (FE), using food as bait, was designed. First, focal ischemia and chronic unpredictable mild stress (CUMS) were used to establish a PSD model in rats. FE was then performed for 4 weeks. Body weight and behavioral assessments were conducted at the end of the 4th and 8th weeks. RESULTS: After 8 weeks, the results revealed that, compared with the PSD group, the behavioral scores of the rats in the PSD/FE group were significantly improved, the expression of Iba-1 in the affected frontal lobe and striatum was decreased, and serum levels of IL-6 and the IL-6/IL-10 ratio were downregulated. However, the ratio of residual brain volume in rats that had experienced CUMS was significantly less than that in the stroke group. CONCLUSION: FE can alleviate the behavioral scores of PSD rats, and its mechanism may be related to a modulation of the immune-inflammation response of microglia. Furthermore, chronic, persistent stress may increase the volume of cerebral infarction after stroke.

Effects of foraging exercise on behavior and the expression of 5-hydroxytryptamine 1A and transforming growth factor β1 in the frontal lobes of rats modelling post-stroke depression / 中华物理医学与康复杂志

Objective:To explore the effect of foraging exercise (FE) on the behavior of rats with post-stroke depression (PSD) and the expression of 5-Hydroxytryptamine 1A (5-HT1A) receptor and transforming growth factor β1 (TGF-β1) in their frontal lobes.Methods:Thirty-six healthy male Sprague-Dawley rats were randomly divided into an ischemia-reperfusion (I/R) group, a PSD group and a PSD+ FE (FE) group, each of 12. The right middle cerebral artery of each was occluded using the thread occlusion method with 1.5h of ischemia. In the PSD and FE groups, mild stimulation was administered at unpredictable intervals over 3 weeks beginning 1 week after the successful modeling. The rats in the I/R group were raised in a group. Those in the PSD group were raised in individual cages. Those in the FE group were raised in a single cage and foraged freely for a total of 4 weeks. Four and eight weeks after the modeling, the body weights were measured, and the open field, social interaction (SIT) and sugar preference tests were administered to all of the groups. Four weeks later, all of the rats were sacrificed and their brains were sliced and stained. The expression of 5-HT1A receptor and TGF-β1 in the frontal lobe was detected using western blotting.Results:One week after modeling, there was no significant difference in average body weight or the average behavioral scores among the three groups. After four weeks the PSD and FE groups had significantly lower average body weight than the I/R group, fewer counts of rearing and grid crossing, longer SIT latency, less interaction time and lower average sugar preference (all significant differences). After eight weeks the average body weight had increased in each group. SIT latency had shortened and interaction time had increased in the FE group, and the rearing and grid crossing counts and sugar preference had increased in the PSD and FE groups. At that point the FE group had significantly greater average body weight than the PSD group, more counts of rearing and grid crossing, shorter SIT latency, increased interaction time, and greater sugar preference. The ratio of residual brain volume in the right hemisphere of the PSD and FE groups was significantly lower on average than in the I/R group. However, there was no significant difference in the right residual brain volume ratio between the PSD and FE groups. Staining revealed that the pathological changes in the frontal lobes of the FE group had been significantly relieved compared with the PSD group. Eight weeks after the operation the increases in average 5-HT 1A receptor and TGF-β1 levels in the FE group were significantly greater than in the PSD group.Conclusion:Foraging can relieve the depressive symptoms of rats modeling post-stoke depression. The mechanism may be related to alleviating the pathological damage and increasing the expression of 5-HT1AR and TGF-β1 in the frontal lobe. Early chronic stress may increase the volume of cerebral infarction, at least in rats.

Systematic Review and Meta-Analysis of the Efficacy of MLC901 (NeuroAiD IITM) for Acute Ischemic Brain Injury in Animal Models.

INTRODUCTION: Moleac (MLC) 901 is a traditional Chinese medication approved by the Sino Food and Drug Administration in 2001 for treating stroke. This study aims to analyze the efficacy of MLC901 in animal stroke models after medial cerebral artery occlusion (MCAO). METHODS: Literature selection was performed according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) 2015. Inclusion criteria for the experimental studies were the use of animal models, publication in English between 1990 and 2020, information regarding the intervention technique used, and outcomes regarding the efficacy of MLC901 administration. RESULTS: MLC901 administration resulted in significantly less infarction volume by a mean difference of 17.17 compared to the control group (p < .00001). The MLC901 group resulted in significant improvement in 5-bromo-20-deoxyuridine (BrdU)-positive cells expression by a mean difference of 662.79 (p < .00001) and neurological function, which was indicated by a mean difference in the Bederson Neurological Outcome Score of 1.40 (p < .00001). CONCLUSIONS: MLC901 administration in an animal stroke model resulted in a better reduction in infarction volume and improvement in BrdU expression and neurologic function. These data could help in further determining the efficacy of MLC901 for acute ischemic brain injury in humans.

Splenic non-infarction volume determines a clinically significant hepatic venous pressure gradient response to partial splenic embolization in patients with cirrhosis and hypersplenism.

BACKGROUND: This study aimed to investigate changes in the hepatic venous pressure gradient (HVPG) by partial splenic embolization (PSE) and to identify the determinants of a clinically meaningful postoperative HVPG reduction. METHODS: Sixty-eight patients with cirrhosis and hypersplenism who underwent PSE at our department between September 2007 and June 2020 were included. The HVPG was evaluated pre- and immediately post-PSE. The patients were divided into three groups according to their preprocedural HVPG: low-HVPG (< 10 mmHg, n = 22), intermediate-HVPG (10 mmHg ≤ HVPG < 16 mmHg, n = 33), and high-HVPG (≥ 16 mmHg, n = 13). RESULTS: Overall, PSE significantly reduced HVPG from 12.2 ± 4.0 to 9.4 ± 3.6 mmHg (p < 0.01) with a relative decrease of 22.2 ± 20.4%. In addition, HVPG reductions were 19.4 ± 28.7%, 24.0 ± 15.9%, and 22.5 ± 13.3% in the low-, intermediate-, and high-HVPG groups, respectively, indicating no significant difference in HVPG reduction between the groups. An HVPG decrease of ≥ 20% from the baseline, defined in this study as a clinically significant HVPG response to PSE, was achieved in 55.9% of all patients. Multivariate logistic regression and receiver operating characteristic curve analyses identified splenic non-infarction volume as an independent determinant of a 20% decrease in HVPG (p < 0.05), with a cut-off of 139.2 cm3 (sensitivity, 76.3%; specificity, 60.0%; p < 0.05). CONCLUSIONS: The splenic non-infarction volume, namely the residual functional spleen volume, independently determines a clinically significant HVPG response to PSE in patients with cirrhosis and hypersplenism.

Comparison of a Bayesian estimation algorithm and singular value decomposition algorithms for 80-detector row CT perfusion in patients with acute ischemic stroke.

PURPOSE: A variety of postprocessing algorithms for CT perfusion are available, with substantial differences in terms of quantitative maps. Although potential advantages of a Bayesian estimation algorithm are suggested, direct comparison with other algorithms in clinical settings remains scarce. We aimed to compare performance of a Bayesian estimation algorithm and singular value decomposition (SVD) algorithms for the assessment of acute ischemic stroke using an 80-detector row CT perfusion. METHODS: CT perfusion data of 36 patients with acute ischemic stroke were analyzed using the Vitrea implemented a standard SVD algorithm, a reformulated SVD algorithm and a Bayesian estimation algorithm. Correlations and statistical differences between affected and contralateral sides of quantitative parameters (cerebral blood volume [CBV], cerebral blood flow [CBF], mean transit time [MTT], time to peak [TTP] and delay) were analyzed. Agreement of the CT perfusion-estimated and the follow-up diffusion-weighted imaging-derived infarct volume were evaluated by nonparametric Passing-Bablok regression analysis. RESULTS: CBF and MTT of the Bayesian estimation algorithm were substantially different and showed a better correlation with the standard SVD algorithm (ρ = 0.78 and 0.80, p < 0.001) than with the reformulated SVD algorithm (ρ = 0.59 and 0.39, p < 0.001). There is no significant difference in MTT only when using the reformulated SVD algorithm (p = 0.217). Regarding the regression lines, the slope and intercept were nearly ideal with the Bayesian estimation algorithm (y = 2.42 x-6.51; ρ = 0.60, p < 0.001) in comparison with the SVD algorithms. CONCLUSIONS: The Bayesian estimation algorithm can lead to a better performance compared with the SVD algorithms in the assessment of acute ischemic stroke because of better delineation of abnormal perfusion areas and accurate estimation of infarct volume.

Novel Metabolites as Potential Indicators of Ischemic Infarction Volume: a Pilot Study.

Metabolomics may identify biomarkers for acute ischemic stroke (AIS). Previously, circulating metabolites were compared in AIS and healthy controls without accounting for stroke size. The goal of this study was to identify metabolites that associate with the volume of AIS. We prospectively analyzed 1554 serum metabolites in the acute (72 h) and chronic (3-6 months) stages of 60 ischemic stroke patients. We calculated infarct volume using diffusion-weighted images with MR segmentation software and associated the volume with stage-specific metabolites, acute-to-chronic stage changes, and multiple mixed regression in metabolite concentrations using multivariate regression analysis. We used the two-stage Benjamini and Hochberg (TSBH) procedure for multiple testing. Four unknown metabolites at the acute stage significantly associated with infarct volume: X24541, X24577, X24581, and X2482 (all p < 0.01). Nine metabolites at the chronic stage are significantly associated with infarct volume: indolpropinate, alpha ketoglutaramate, picolinate, X16087, X24637, X24576, X24577, X24582, X24581 (all p < 0.048). Infarct volume is also associated with significant changes in serum concentrations of twenty-seven metabolites, with p values from 0.01 to 1.48 × 10-7, and on five metabolites using mixed regression model. This prospective pilot study identified several metabolites associated with the volume of ischemic infarction. Confirmation of these findings on a larger dataset would help characterize putative pathways underlying the size of ischemic infarction and facilitate the identification of biomarkers or therapeutic targets.

Relationship between 25-hydroxyvitamin D and infarction volume in patients with acute ischemic stroke in anterior circulation / 中华危重病急救医学

Objective:To investigate the correlation between the level of serum 25-hydroxyvitamin D [25(OH)D] and infarction volume in patients with acute ischemic stroke (AIS) with internal carotid artery system (anterior circulation).Methods:A prospective cohort study was conducted. Patients with AIS admitted to the department of emergency of Beijing Boai Hospital from October 2017 to September 2019 were enrolled. Nutritional risk screening 2002 (NRS 2002) were assessed in all cases within 24 hours after enrollment. Fasting venous blood was collected for biochemical analysis, including albumin (ALB), homocysteine (HCY), uric acid (UA), hypersensitive C-reactive protein (hs-CRP), etc. Serum 25(OH)D level was detected by electrochemiluminescence immunoassay. Magnetic resonance imaging (MRI) was performed to calculate the volume of cerebral infarction. According to the volume of cerebral infarction, the patients were divided into small volume (≤ 1 cm 3) group, medium volume (1 cm 3 < infarct volume < 20 cm 3) group and large volume (≥20 cm 3) group. The differences of serum 25(OH)D and other indicators in each group were compared; the influencing factors of infarct volume were analyzed by Logistic regression; and the goodness of fit of regression model was tested by Hosmer-Lemeshow (HL). Results:A total of 224 patients with AIS were enrolled, 92 in small volume group, 90 in medium volume group and 42 in large volume group, and there was no significant difference in serum 25(OH)D level among small, medium and large volume groups [μg/L: 13.21 (7.47, 19.33), 11.20 (7.00, 15.07), 9.19 (6.30, 17.10), H = 4.994, P = 0.082]. There were 124 patients with AIS in anterior circulation, 45, 56 and 23 patients in the small, medium and large volume groups, respectively, with the increase of the cerebral infarction volume, the serum 25(OH)D level in small, medium and large volume groups decreased gradually, and the difference was statistically significant [μg/L: 13.22 (9.00, 19.65), 10.41 (6.72, 14.92), 8.30 (4.70, 11.30), H = 11.068, P = 0.004]. In addition, with the increase of the cerebral infarction volume, the older the patients with AIS in anterior circulation [years old: 63.0 (54.0, 75.5), 76.0 (63.0, 84.0), 82.0 (67.5, 85.0), H = 14.981, P = 0.001], the higher the nutritional risk ratio (35.6%, 53.6%, 73.9%, χ2 = 9.271, P = 0.010), the higher the serum hs-CRP level [mg/L: 1.91 (0.92, 3.40), 4.10 (1.73, 22.42), 19.74 (4.02, 68.81), H = 21.477, P < 0.001], and the lower the ALB level (g/L: 42.30±12, 38.11±5.06, 35.14±5.49, F = 19.347, P < 0.001). After adjusting for age, gender, atrial fibrillation, nutritional risk, hs-CRP and other confounding factors, serum 25(OH)D was an independent protective factor for the infarct volume of AIS in anterior circulation [odds ratio ( OR) = 0.962, P = 0.040], For every 10 μg/L decrease of 25(OH)D, the risk of one grade increase in infarction volume was increased by 47.7% respectively (goodness of fit: χ2 = 5.357, P = 0.719). Conclusion:The low serum 25(OH)D level was associated with the increase of infarct volume in the anterior circulation cerebral infarction, and early detection of serum 25(OH)D level can help risk stratification of AIS patients.

Prognostic value of cerebral infarction coefficient in patients with massive cerebral infarction.

OBJECTIVE: We proposed the concept of the cerebral infarction coefficient, which is cerebral infarction volume/brain volume. This study aimed to evaluate the prognostic value of the cerebral infarction coefficient in patients with massive cerebral infarction (MCI). METHODS: According to the modified Rankin score, 71 patients with acute MCI were divided into good prognosis and poor prognosis groups. Clinical and imaging data of the two groups were collected and univariate analysis was carried out. If there were significant differences in the data between the two groups, binary logistic regression analysis was performed. RESULTS: The poor prognosis group had a significantly higher cerebral infarction volume, cerebral infarction coefficient, and D-dimer levels, older age, the highest body temperature, a higher rate of a history of atrial fibrillation, and a lower rate of a history of hypertension compared with the good prognosis group (all P < 0.05). Binary logistic regression analysis showed that the cerebral infarction coefficient was an independent risk factor for a poor prognosis of patients with MCI (P < 0.05, 95 % confidence interval, 2.091, 42.562), and the odds ratio was 8.506. The area under the receiver operating characteristic curve for the cerebral infarction coefficient was 0.753. When the cut-off value was 7.8 %, the sensitivity of predicting a poor prognosis of patients with MCI was 92.5 %. CONCLUSION: The cerebral infarction coefficient may have predictive value in determining the prognosis of patients with MCI.

Antioxidative effects of a novel dietary supplement Neumentix in a mouse stroke model.

BACKGROUND: During an acute stroke, reactive oxygen species are overproduced and the endogenous antioxidative defense systems are disrupted. Therefore, antioxidative therapy can be a promising scheme to reduce the severity of stroke. Neumentix is a novel antioxidative supplement produced from a patented mint line and contains a high content of rosmarinic acid (RA). Although Neumentix has proven diverse efficacy and safety in clinical trials, its effect on strokes is unclear. METHODS: Mice that were treated with Neumentix or vehicle for 14 days underwent transient middle cerebral artery occlusion (tMCAO) for 60 min. Mice were sacrificed 5 days after tMCAO. RESULTS: Neumentix preserved body weight after tMCAO, showed a high antioxidative effect in serum, and reduced infarction volume compared to the vehicle. The expression of 4-hydroxy-2-nonenal, Nε-(carboxymethyl) lysine, and 8-hydroxy-2'-deoxyguanosine was reduced in Neumentix-treated mice. CONCLUSION: The antioxidative effect of Neumentix was confirmed. This is the first report to demonstrate the antioxidative effect of Neumentix on strokes.

Relation of infarction location and volume to vertigo in vertebrobasilar stroke.

OBJECTIVE: Vertigo is a common presentation of vertebrobasilar stroke. Anecdotal reports have shown that vertigo occurs more often in multiple than in single brainstem or cerebellar infarctions. We examined the relation between the location and volume of infarction and vertigo in patients with vertebrobasilar stroke. METHODS: Consecutive patients with vertebrobasilar stroke were prospectively recruited. The infarction location and volume were assessed in the diffusion-weighted magnetic resonance imaging. RESULTS: Fifty-nine patients were included, 32 (54.2%) with vertigo and 27 (45.8%) without vertigo. The infarction volume did not correlate with National Institute of Health Stroke Scale (NIHSS) score on admission (Spearman ρ = .077, p = .56) but correlated with modified Rankin Scale (ρ = .37, p = .004) on discharge. In the vertigo group, the proportion of men was lower (53.1% vs. 77.8%, p = .049), fewer patients had focal neurological deficits (65.6% vs. 96.3%, p = .004), patients tended to present later (median [IQR] was 7.5 [4-46] vs. 4 [2-12] hours, p = .052), numerically fewer patients received intravenous thrombolysis (15.6% vs. 37%, p = .06), and the total infarction volume was larger (5.6 vs. 0.42 cm3 , p = .008) than in nonvertigo group. In multivariate logistic regression, infarction location either in the cerebellum or in the dorsal brainstem (odds ratio [OR] 16.97, 95% CI 3.1-92.95, p = .001) and a total infarction volume of >0.48 cm3 (OR 4.4, 95% CI 1.05-18.58, p = .043) were related to vertigo. In another multivariate logistic regression, after adjusting for age, sex, intravenous thrombolysis, serum level of white blood cells, and atrial fibrillation, vertigo independently predicted a total infarction volume of >0.48 cm3 (OR 5.75, 95% CI 1.43-23.08, p = .01). CONCLUSION: Infarction location in the cerebellum and/or dorsal brainstem is an independent predictor of vertigo. Furthermore, larger infarction volume in these structures is associated with vertigo. A considerable proportion of patients with vascular vertigo present without focal neurological deficits posing a diagnostic challenge. National Institute of Health Stroke Scale is not sensitive for vertebrobasilar stroke.

High On-Treatment Platelet Reactivity Affects the Extent of Ischemic Lesions in Stroke Patients Due to Large-Vessel Disease.

BACKGROUND: Excessive platelet activation and aggregation plays an important role in the pathogenesis of ischemic stroke. Correlation between platelet reactivity and ischemic lesions in the brain shows contradictory results and there are not enough data about the potential role of stroke etiology and its relationships with chronic lesions. The aim of this study is to assess the relationship between platelet reactivity and the extent of ischemic lesions with the particular role of etiopathogenesis. METHODS: The study involved 69 patients with ischemic stroke, including 20 patients with large-vessel disease and 49 patients with small-vessel disease. Evaluation of platelet reactivity was performed within 24 h after the onset of stroke using two aggregometric methods (impedance and optical), while ischemic volume measurement in the brain was performed using magnetic resonance imaging (in diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences) at day 2-5 after the onset of stroke. RESULTS: In the large-vessel disease subgroup, a correlation was found between platelet reactivity and acute ischemic focus volume (correlation coefficient (R) = 0.6858 and p = 0.0068 for DWI; R = 0.6064 and p = 0.0215 for FLAIR). Aspirin-resistant subjects were significantly more likely to have a large ischemic focus (Odds Ratio (OR) = 45.00, 95% Confidence Interval (CI) = 1.49-135.36, p = 0.0285 for DWI; OR = 28.00, 95% CI = 1.35-58.59, p = 0.0312 for FLAIR) than aspirin-sensitive subjects with large-vessel disease. CONCLUSION: In patients with ischemic stroke due to large-vessel disease, high on-treatment platelet reactivity affects the extent of acute and chronic ischemic lesions.

The Short-Term Effects of Isolated Traumatic Brain Injury on the Heart in Experimental Healthy Rats.

BACKGROUND: To date, cardiac dysfunction after traumatic brain injury (TBI) has not been consistent. In this study, we hypothesized that TBI may play a role in the development of new-onset cardiac dysfunction in healthy experimental rats. MATERIALS AND METHODS: Anesthetized healthy male Sprague-Dawley rats were divided into two groups: a sham-operated control group and a TBI group. The brain was injured with 2.4 atm percussion via a fluid percussion injury model. During the 120 min after TBI, we continuously measured brain parameters, including intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and cardiac parameters, such as heart rate (HR), inter-ventricular septum dimension (IVSD), left ventricular internal dimension diastole (LVIDd), end-diastolic volume (EDV), ejection fraction (EF), fractional shortening (FS), and LV mass diastole (LVd mass) by cardiac echo. On days 1, 3, 7, and 14 after TBI, the brain damage volume was evaluated with triphenyltetrazolium chloride; the physiological parameters of the heart, including HR, IVSd, LVIDd, EDV, EF, FS, and LVd mass, were evaluated with cardiac echo; the morphology of cardiomyocytes was examined by hematoxylin and eosin (HE) and Masson trichrome staining; and the biomarkers of cardiac injury troponin I and B-type natriuretic peptide (BNP) were also examined. RESULTS: Compared to sham-operated controls, the TBI groups had higher ICP, lower CPP, and higher brain neuronal apoptosis and infarction contusion volume. The impact of TBI on heart function showed hyperdynamic response trends in IVSd, LVIDd, EDV, EF, FS, and LVd mass within 30 min after TBI; however, EF and FS exhibited eventual decreasing trends. Simultaneously, the values of the biomarkers troponin I and BNP were within normal limits, and HE and Mass trichrome staining revealed no significant differences between the sham-operated control group and the TBI group. CONCLUSIONS: Our results suggest that TBI due to 2.4 atm fluid percussion injury in healthy experimental rats may cause significant damage to the brain and affect the heart function as investigated by cardiac echo but not as investigated by HE and Masson trichrome stainings or troponin I and BNP evaluation.

Neuron-specific enolase is correlated with lesion topology, relative infarct volume and outcome of symptomatic NAIS.

OBJECTIVE: To correlate neuron-specific enolase (NSE) levels in cerebrospinal fluid (CSF) in neonate infants with symptomatic neonatal arterial ischaemic stroke (NAIS) with the arterial distribution of infarct, infarct volume and outcome. DESIGN: Prospective observational multicentre cohort. SETTING: Three paediatric university hospitals in Spain. SUBJECTS: Thirty-eight neonates with more than 35 weeks' gestational age between 2006 and 2016 were studied. They were diagnosed with NAIS by MRI. They underwent a lumbar puncture to measure CSF-NSE concentrations within 96 hours after the onset of symptoms. Sixty-seven neonates admitted with suspected infections served as controls. We used a classification based on the arterial distribution, and the lesions were segmented with ITK-Snap software to determine their volume. Neurodevelopment was assessed at 24 months using the Bayley-III, Gross Motor Function Classification System and Bimanual Fine Motor Function. RESULTS: CSF-NSE levels were higher in patients with symptomatic NAIS when compared with controls. Neonates with multifocal NAIS and with NAIS located in middle cerebral artery (MCA)-M1 arterial territory showed higher CSF-NSE levels when compared with cases with MCA-M2-M3-M4 territories (p<0.001). A significant correlation was found between CSF-NSE and relative infarction volume (rs=0.597; p<0.001). CSF-NSE values were higher in those infants with symptomatic NAIS with adverse outcome compared with infants with good development (p=0.020). Infants with CSF-NSE values above 55 ng/mL had an OR of adverse outcome of 6.48 (95% CI 1.48 to 28.33). CONCLUSIONS: CSF-NSE is a potential early prognostic biomarker after an NAIS due to the relation between volume, topology and neurodevelopment at 2 years of age.

Development of a three-channel automatic climbing training system for rat rehabilitation after ischemic stroke

This paper reports the development of a three-channel automatic speed-matching climbing training system that could train three rats at the same time for rehabilitation after an ischemic stroke. An infrared (IR) remote sensor was installed at the end of each channel to monitor the real-time position of a climbing rat. This research was carried out in five stages: i) system design; ii) hardware circuit; iii) running speed control; iv) functional testing; and v) verification using an animal model of cerebral stroke. The rehabilitated group significantly outperformed the middle cerebral artery occlusion (MCAo) sedentary group in the rota-rod and inclined plate tests 21 days after a stroke. The rehabilitated group also had a cerebral infarction volume of 28.34±19.4%, far below 56.81±18.12% of the MCAo group 28 days after the stroke, validating the effectiveness of this training platform for stroke rehabilitation. The running speed of the climbing rehabilitation training platform was designed to adapt to the physical conditions of subjects, and overtraining injuries can be completely prevented accordingly.

MiR-150-5p protects rats from middle cerebral artery occlusion by inhibiting the toll-like receptor-5/nuclear factor-kappa B p65 signaling pathway / 中国组织工程研究

BACKGROUND: There is an inflammatory response in the lesion tissue of ischemic cerebral infarction, and the expression of miR-150-5p is significantly decreased. Whether miR-150-5p inhibits the release of inflammatory factors and alleviates the injury of ischemic cerebral infarction tissue through the Toll-like receptor-5/nuclear factor-KB pathway remains unclear. OBJECTIVE: To investigate the role and preliminary mechanism of miR-150-5p in ischemic cerebral infarction in rats. METHODS: (1) The rat models of middle cerebral artery occlusion were constructed and the rat models were divided into five groups: Control, miR-150-5p agomir, agomir control, miR-150-5p antagomir and antagomir control groups. (2) The rats in the control group was given the intracerebroventricular injection of normal saline, and the rats in the latter four groups were given the intracerebroventricular injection of miR-150-5p agomir (miR-150-5p agonist), agomir negative control, miR150-5p antagomir (miR150-5p inhibitor) and antagomir negative control, respectively. (3) After 7 days, the brain was graded by modified neurological severity score, the cerebral infarct volume was measured by MRI, and the histopathological changes were observed by hematoxylin-eosin staining. The expression levels of miR-150-5p, interleukin-6, tumor necrosis factor-a, Toll-like receptor-5 and nuclear factor-KB p65 in brain tissues were detected by qRT-PCR, ELISA and western blot assay, respectively. The target relationship between miR150-5p and Toll-like receptor-5 was verified by luciferase assay by retrieving the bioinformatics website Targetscan to predict the binding sites of miR-150-5p and Toll-like receptor-5. RESULTS AND CONCLUSION: (1) Compared with the control group, the modified neurological severity score, and levels of interleukin-6, tumor necrosis factor-a, Toll-like receptor-5 and nuclear factor-KB p65 proteins were significantly decreased in the miR-150-5p agomir group (P 0.05). (3) TargerScan website prediction results and luciferase reporter gene analysis results showed that miR-150-5p and Toll-like receptor-5 had a targeted binding site. (4) These results imply that miR-150-5p can inhibit the inflammatory signaling pathway of Toll-like receptor-5/nuclear factor-KB p65 in brain injury caused by ischemia and reduce the inflammatory response, thereby alleviating the damage of nerve function and playing a protective role.