Stroke:干细胞疗法可有效治疗中风

正患有中风的患者在经过向大脑中注射干细胞治疗,能够明显地提高其讲话能力、身体强度以及行动力。其中一些患者甚至能够重新行走。这一临床试验的成功意味着我们低估了大脑自愈的能力,也许有一天这种疗法能够使大脑重新恢复功能。"一位71岁的老年女性在治疗开始前仅仅能够活动左手大拇指",该研究的首席研究员,来自斯坦福大学的神经科医生Gary Steinberg说道:"如今她能够行走以及将手举过头顶"。     

Stroke:权威研究——PM2.5的确损伤大脑

<正>空气污染,甚至是适度水平的污染都被认为是增加中风风险的因子,近日,一篇发表于国际杂志Stroke上的研究论文中,来自波士顿大学医学院等处的研究人员通过研究发现,长期暴露于空气污染中会促进大脑结构的损伤,并且损伤中老年个体的认知功能。文章中研究者对900多名弗兰明汉心脏研究中心的参与者进行研究发现了个体大脑结构变小及隐秘脑梗塞的发病原因,隐秘脑梗塞是一种     

Blood Glutathione S-Transferase-π as a Time Indicator of Stroke Onset

Background

Ability to accurately determine time of stroke onset remains challenging. We hypothesized that an early biomarker characterized by a rapid increase in blood after stroke onset may help defining better the time window during which an acute stroke patient may be candidate for intravenous thrombolysis or other intravascular procedures.

Methods

The blood level of 29 proteins was measured by immunoassays on a prospective cohort of stroke patients (N = 103) and controls (N = 132). Mann-Whitney U tests, ROC curves and diagnostic odds ratios were applied to evaluate their clinical performances.

Results

Among the 29 molecules tested, GST-π concentration was the most significantly elevated marker in the blood of stroke patients (p<0.001). More importantly, GST-π displayed the best area under the curve (AUC, 0.79) and the best diagnostic odds ratios (10.0) for discriminating early (N = 22, <3 h of stroke onset) vs. late stroke patients (N = 81, >3 h after onset). According to goal-oriented distinct cut-offs (sensitivity(Se)-oriented: 17.7 or specificity(Sp)-oriented: 65.2 ug/L), the GST-π test obtained 91%Se/50%Sp and 50%Se/91%Sp, respectively. Moreover, GST-π showed also the highest AUC (0.83) and performances for detecting patients treated with tPA (N = 12) compared to ineligible patients (N = 103).

Conclusions

This study demonstrates that GST-π can accurately predict the time of stroke onset in over 50% of early stroke patients. The GST-π test could therefore complement current guidelines for tPA administration and potentially increase the number of patients accessing thrombolysis.     

Pre-Existing Hypertension Dominates γδT Cell Reduction in Human Ischemic Stroke

T lymphocytes may play an important role in the evolution of ischemic stroke. Depletion of γδT cells has been found to abrogate ischemia reperfusion injury in murine stroke. However, the role of γδT cells in human ischemic stroke is unknown. We aimed to determine γδT cell counts and γδT cell interleukin 17A (IL-17A) production in the clinical setting of ischemic stroke. We also aimed to determine the associations of γδT cell counts with ischemic lesion volume, measures of clinical severity and with major stroke risk factors. Peripheral blood samples from 43 acute ischemic stroke patients and 26 control subjects matched on race and gender were used for flow cytometry and complete blood count analyses. Subsequently, cytokine levels and gene expression were measured in γδT cells. The number of circulating γδT cells was decreased by almost 50% (p = 0.005) in the stroke patients. γδT cell counts did not correlate with lesion volume on magnetic resonance diffusion-weighted imaging or with clinical severity in the stroke patients, but γδT cells showed elevated levels of IL-17A (p = 0.048). Decreased γδT cell counts were also associated with older age (p = 0.004), pre-existing hypertension (p = 0.0005) and prevalent coronary artery disease (p = 0.03), with pre-existing hypertension being the most significant predictor of γδT cell counts in a multivariable analysis. γδT cells in human ischemic stroke are reduced in number and show elevated levels of IL-17A. A major reduction in γδT lymphocytes also occurs in hypertension and may contribute to the development of hypertension-mediated stroke and vascular disease.     

Impaired Limb Shortening following Stroke: What’s in a Name?

Background

Difficulty advancing the paretic limb during the swing phase of gait is a prominent manifestation of walking dysfunction following stroke. This clinically observable sign, frequently referred to as ‘foot drop’, ostensibly results from dorsiflexor weakness.

Objective

Here we investigated the extent to which hip, knee, and ankle motions contribute to impaired paretic limb advancement. We hypothesized that neither: 1) minimal toe clearance and maximal limb shortening during swing nor, 2) the pattern of multiple joint contributions to toe clearance and limb shortening would differ between post-stroke and non-disabled control groups.

Methods

We studied 16 individuals post-stroke during overground walking at self-selected speed and nine non-disabled controls who walked at matched speeds using 3D motion analysis.

Results

No differences were detected with respect to the ankle dorsiflexion contribution to toe clearance post-stroke. Rather, hip flexion had a greater relative influence, while the knee flexion influence on producing toe clearance was reduced.

Conclusions

Similarity in the ankle dorsiflexion, but differences in the hip and knee, contributions to toe clearance between groups argues strongly against dorsiflexion dysfunction as the fundamental impairment of limb advancement post-stroke. Marked reversal in the roles of hip and knee flexion indicates disruption of inter-joint coordination, which most likely results from impairment of the dynamic contribution to knee flexion by the gastrocnemius muscle in preparation for swing. These findings suggest the need to reconsider the notion of foot drop in persons post-stroke. Redirecting the focus of rehabilitation and restoration of hemiparetic walking dysfunction appropriately, towards contributory neuromechanical impairments, will improve outcomes and reduce disability.     

Copeptin,Procalcitonin and Routine Inflammatory Markers–Predictors of Infection after Stroke

Background

Early predictors for the development of stroke-associated infection may identify patients at high risk and reduce post-stroke infection and mortality.

Methods

In 383 prospectively enrolled acute stroke patients we assessed time point and type of post-stroke infections (i.e. pneumonia, urinary tract infection (UTI) other infection (OI)). Blood samples were collected on admission, and days 1, and 3 to assess white blood cells (WBC), monocytes, C-reactive protein (CRP), procalcitonin (PCT), and copeptin. To determine the magnitude of association with the development of infections, odds ratios (OR) were calculated for each prognostic blood marker. The discriminatory ability of different predictors was assessed, by calculating area under the receiver operating characteristic curves (AUC). Prognostic models including the three parameters with the best performance were identified.

Results

Of 383 patients, 66 (17.2%) developed an infection after onset of stroke. WBC, CRP, copeptin and PCT were all independent predictors of any infection, pneumonia and UTI developed at least 24 hours after measurements. The combination of the biomarkers WBC, CRP and copeptin (AUC: 0.92) and WBC, CRP and PCT (AUC: 0.90) showed a better predictive accuracy concerning the development of pneumonia during hospitalization compared to each marker by itself (p-Wald <0.0001).

Conclusion

Among ischemic stroke patients, copeptin, PCT, WBC and CRP measured on admission were predictors of infection in general, and specifically for pneumonia and UTI within 5 days after stroke. The combination of these biomarkers improved the prediction of patients who developed an infection.     

Cytidine 5′-Diphosphocholine (CDP-Choline) in Stroke and Other CNS Disorders

Brain phosphatidylcholine (PC) levels are regulated by a balance between synthesis and hydrolysis. Pro-inflammatory cytokines such as tumor necrosis factor- (TNF-) and interleukin-1 (IL-1/) activate phospholipase A₂ (PLA₂) and PC-phospholipase C (PC-PLC) to hydrolyze PC. PC hydrolysis by PLA₂ releases free fatty acids including arachidonic acid, and lyso-PC, an inhibitor of CTP-phosphocholine cytidylyltransferase (CCT). Arachidonic acid metabolism by cyclooxygenases/lipoxygenases is a significant source of reactive oxygen species. CDP-choline might increase the PC levels by attenuating PLA₂ stimulation and loss of CCT activity. TNF- also stimulates proteolysis of CCT. TNF- and IL-1 are induced in brain ischemia and may disrupt PC homeostasis by increasing its hydrolysis (increase PLA₂ and PC-PLC activities) and inhibiting its synthesis (decrease CCT activity). The beneficial effects of CDP-choline may result by counteracting TNF- and/or IL-1 mediated events, integrating cytokine biology and lipid metabolism. Re-evaluation of CDP-choline phase III stroke clinical trial data is encouraging and future trails are warranted. CDP-choline is non-xenobiotic, safe, well tolerated, and can be considered as one of the agents in multi-drug treatment of stroke.     

Does Hepatitis C Virus Infection Increase Risk for Stroke? A Population-Based Cohort Study

Background

The relationship between hepatitis C virus infection and risk of stroke remains inconsistent. This study evaluates the risk of stroke in association with chronic hepatitis C infection in a longitudinal population-based cohort.

Methods

We identified 4,094 adults newly diagnosed with hepatitis C infection in 2002–2004 from the Taiwan National Health Insurance Research Database. Comparison group consisted of 16,376 adults without hepatitis C infection randomly selected from the same dataset, frequency matched by age and sex. Events of stroke from 2002–2008 were ascertained from medical claims (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM, codes 430–438). Multivariate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for potential associated factors including HCV infection, age, sex, low-income status, urbanization, cessation of cigarette smoking, alcohol-related illness, obesity, history of chronic diseases and medication use.

Findings

During 96,752 person-years of follow-up, there were 1981 newly diagnosed stroke cases. The HRs of stroke associated with medical conditions such as hypertension, diabetes and heart disease were 1.48 (95% CI 1.33 to 1.65), 1.23 (95% CI 1.11 to 1.36) and 1.17 (95% CI 1.06 to 1.30), respectively, after adjustment for covariates. The cumulative risk of stroke for people with hepatitis C and without hepatitis C infections was 2.5% and 1.9%, respectively (p<0.0001). Compared with people without hepatitis C infection, the adjusted HR of stroke was 1.27 (95% CI 1.14 to 1.41) for people with hepatitis C infection.

Conclusion

Chronic hepatitis C infection increases stroke risk and should be considered an important and independent risk factor.     

Is There a Link between Exertional Heat Stroke and Susceptibility to Malignant Hyperthermia?

Objective

The identification of a predisposition toward malignant hyperthermia (MH) as a risk factor for exertional heat stroke (EHS) remains a matter of debate. Such a predisposition indicates a causal role for MH susceptibility (MHS) after EHS in certain national recommendations and has led to the use of an in vitro contracture test (IVCT) to identify the MHS trait in selected or unselected EHS patients. The aim of this study was to determine whether the MHS trait is associated with EHS.

Methods

EHS subjects in the French Armed Forces were routinely examined for MHS after experiencing an EHS episode. This retrospective study compared the features of IVCT-diagnosed MHS (iMHS) EHS subjects with those of MH-normal EHS patients and MH patients during the 2004–2010 period. MHS status was assessed using the European protocol.

Results

During the study period, 466 subjects (median age 25 years; 31 women) underwent MHS status investigation following an EHS episode. None of the subjects reported previous MH events. An IVCT was performed in 454 cases and was diagnostic of MHS in 45.6% of the study population, of MH susceptibility to halothane in 18.5%, of MH susceptibility to caffeine in 9.9%, and of MH susceptibility to halothane and caffeine in 17.2%. There were no differences in the clinical features, biological features or outcomes of iMHS EHS subjects compared with those of MH-normal or caffeine or halothane MHS subjects without known prior EHS episode. The recurrence rate was 12.7% and was not associated with MH status or any clinical or biological features. iMHS EHS patients exhibited a significantly less informative IVCT response than MH patients.

Conclusions

The unexpected high prevalence of the MHS trait after EHS suggested a latent disturbance of calcium homeostasis that accounted for the positive IVCT results. This study did not determine whether EHS patients have an increased risk of MH, and it could not determine whether MH susceptibility is a risk factor for EHS.     

Post-Stroke Mortality,Stroke Severity,and Preadmission Antipsychotic Medicine Use – A Population-Based Cohort Study

Background and Purpose

It has been suggested that antipsychotic medication may be neuroprotective and may reduce post-stroke mortality, but studies are few and ambiguous. We aimed to investigate the post-stroke effects of preadmission antipsychotic use.

Methods

We conducted a nationwide, population-based cohort study of 81,143 persons admitted with stroke in Denmark from 2003–2010. Using Danish health care databases, we extracted data on preadmission use of antipsychotics and confounding factors. We examined the association between current, former, and never use of antipsychotics and stroke severity, length of hospital stay, and 30-day post-stroke mortality using logistic regression analysis, survival analysis, and propensity score matching.

Results

Current users of antipsychotics had a higher risk of severe or very severe stroke on The Scandinavian Stroke Scale than never users of antipsychotics (adjusted odds ratios, 1.43; 95% CI, 1.29–1.58). Current users were less likely to be discharged from hospital within 30 days of admission than never users (probability of non-discharge, 27.0% vs. 21.9%). Antipsychotics was associated with an increased 30-day post-stroke mortality among current users (adjusted mortality rate ratios, 1.42; 95% CI, 1.29–1.55), but not among former users (adjusted mortality rate ratios, 1.05; 95% CI, 0.98–1.14).

Conclusions

Preadmission use of antipsychotics was associated with a higher risk of severe stroke, a longer duration of hospital stay, and a higher post-stroke mortality, even after adjustment for known confounders. Antipsychotics play an important role in the treatment of many psychiatric conditions, but our findings do not support the hypothesis that they reduce stroke severity or post-stroke mortality.     

Where Do Neurologists Look When Viewing Brain CT Images? An Eye-Tracking Study Involving Stroke Cases

The aim of this study was to investigate where neurologists look when they view brain computed tomography (CT) images and to evaluate how they deploy their visual attention by comparing their gaze distribution with saliency maps. Brain CT images showing cerebrovascular accidents were presented to 12 neurologists and 12 control subjects. The subjects' ocular fixation positions were recorded using an eye-tracking device (Eyelink 1000). Heat maps were created based on the eye-fixation patterns of each group and compared between the two groups. The heat maps revealed that the areas on which control subjects frequently fixated often coincided with areas identified as outstanding in saliency maps, while the areas on which neurologists frequently fixated often did not. Dwell time in regions of interest (ROI) was likewise compared between the two groups, revealing that, although dwell time on large lesions was not different between the two groups, dwell time in clinically important areas with low salience was longer in neurologists than in controls. Therefore it appears that neurologists intentionally scan clinically important areas when reading brain CT images showing cerebrovascular accidents. Both neurologists and control subjects used the "bottom-up salience" form of visual attention, although the neurologists more effectively used the "top-down instruction" form.     

Clinical Manifestation of Depression after Stroke: Is It Different from Depression in Other Patient Populations?

Background

Despite ample research on depression after stroke, the debate continues regarding whether symptoms such as sleep disturbances, loss of energy, changes in appetite and diminished concentration should be considered to be consequences of stroke or general symptoms of depression. By comparing symptoms in depressed and non-depressed stroke patients with patients in general practice and patients with symptomatic atherosclerotic diseases, we aim to further clarify similarities and distinctions of depression after stroke and depression in other patient populations. Based on this, it is possible to determine if somatic symptoms should be evaluated in stroke patients in diagnosing depression after stroke.

Methods

An observational multicenter study is conducted in three hospitals and seven general practices including 382 stroke patients admitted to hospital with a clinical diagnosis of intracerebral hemorrhage or ischemic infarction, 1160 patients in general practice (PREDICT-NL), and 530 patients with symptomatic atherosclerotic diseases (SMART-Medea).

Results

The prevalence of major depressive disorder according to DSM-IV criteria was 14.1% (95% CI 11.0%-18.0%) in the stroke cohort, 5.4% (95% CI 3.8%-7.9%) in the symptomatic atherosclerotic diseases cohort and 12.9% (95% CI 11.1%-15.0%) in the general practice cohorts. Comparing depressed patients of the three cohorts demonstrated broadly similar symptom profiles, as well as comparable levels of individual symptom prevalence. However, the stroke patients suffered more severely from these symptoms than patients in the other populations.

Conclusions

The findings suggest that depression after stroke is not a different type of depression. This finding indicates that all depressive symptoms should be evaluated in stroke patients, including somatic symptoms.     

T2* “Susceptibility Vessel Sign” Demonstrates Clot Location and Length in Acute Ischemic Stroke

Objectives

The aim of our study was to evaluate, in acute ischemic stroke patients, the diagnostic accuracy of the MRI susceptibility vessel sign (SVS) against catheter angiography (DSA) for the detection of the clot and its value in predicting clot location and length.

Materials and Methods

We identified consecutive patients (2006–2012) admitted to our center, where 1.5 T MRI is systematically implemented as first-line diagnostic work-up, with: (1) pre-treatment 6-mm-thick multislice 2D T2* sequence; (2) delay from MRI-to-DSA <3 hrs; (3) no fibrinolysis between MRI and DSA. The location and length of SVS on T2* was independently assessed by three readers, and compared per patient, per artery and per segment, to DSA findings, obtained by two different readers. Clot length measured on T2* and DSA were compared using intra-class correlation coefficient (ICC), Bland & Altman test and Passing & Bablok regression analysis.

Results

On DSA, a clot was present in 85 patients, in 126 of 1190 (10.6%) arteries and 175 of 1870 (9.4%) segments. Sensitivity of the SVS, as sensed by the used protocol at 1.5 T, was 81.1% (69 of 85 patients) and was higher in anterior (55 of 63, 87.3%), than in posterior circulation stroke (14 of 22, 63.6%, p=0.02). Sensitivity/specificity was 69.8/99.6% (per artery) and 76.6/99.7% (per segment). Positive (PPV) and negative predictive value (NPV) and accuracy were all >94%. Inter- and intra-observer ICC was excellent for clot length as measured on T2* (ĸ ≥0.97) and as measured on DSA (ĸ ≥0.94). Correlation between T2* and DSA for clot length was excellent (ICC: 0.88, 95%CI: 0.81–0.92; Bland & Altman: mean bias of 1.6% [95%CI: -4.7 to 7.8%], Passing & Bablok: 0.91).

Conclusions

SVS is a specific marker of clot location in the anterior and posterior circulation. Clot length greater than 6 mm can be reliably measured on T2*.     

Depressive Symptoms and the Risk of Ischemic Stroke in the Elderly—Influence of Age and Sex

Although a relationship between depression and cardiovascular events has been suggested, past study results regarding the risk of stroke in relation to depression by subgroups are ambiguous. The aim of this study was to investigate the influence of depressive symptoms on risk of incident ischemic stroke in elderly according to age and sex. This prospective cohort study followed up 3852 subjects older than 55 years. Baseline depressive symptoms were defined by a score ≥5 on the Geriatric Depression Scale or antidepressant intake. The outcome measure was incident ischemic stroke within 6 years of follow-up. Multivariate Cox-proportional hazard models as well as cumulative survival analyses were computed. A total of 156 ischemic strokes occurred during the study period (24 strokes in the age-group<65 years and 132 strokes in the age-group≥65 years). The distribution of strokes in sex-subgroups was 4.5% in men and 3.7% in women. The multivariate analysis showed an elevated stroke risk (Hazard Ratio (HR): 2.84, 95% CI 1.11–7.29, p = 0.030) in subjects from 55 to 64 years with depressive symptoms at baseline but not in subjects older than 65 years. In the multivariate analysis according to sex the risk was increased in women (HR: 1.62, 95% CI 1.02–2.57, P = 0.043) but not in men. The Cox-regression model for interaction showed a significant interaction between age and sex (HR: 3.24, 95% CI 1.21–8.69, P = 0.020). This study corroborates that depressive symptoms pose an important risk for ischemic stroke, which is particularly remarkable in women and patients younger than 65 years.     

Does Adhesive Capsulitis of the Shoulder Increase the Risk of Stroke? A Population-Based Propensity Score-Matched Follow-Up Study

Objectives

A previous population-based study reported an increased risk of stroke after the occurrence of adhesive capsulitis of the shoulder (ACS), but there were substantial imbalances in the distribution of age and pre-existing vascular risk factors between subjects with ACS and without ACS, which might lead to a confounded association between ACS and stroke. The purpose of the present large-scale propensity score-matched population-based follow-up study was to clarify whether there is an increased stroke risk after ACS.

Methods

We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 22025 subjects with at least two ambulatory visits with the principal diagnosis of ACS in 2001 was enrolled in the ACS group. The non-ACS group consisted of 22025, propensity score-matched subjects without ACS. The stroke-free survival curves for these 2 groups were compared using the Kaplan-Meier method. Stratified Cox proportional hazard regression with patients matched on propensity score was used to estimate the effect of ACS on the occurrence of stroke.

Results

During the two-year follow-up period, 657 subjects in the ACS group (2.98%) and 687 in the non-ACS group (3.12%) developed stroke. The hazard ratio (HR) of stroke for the ACS group was 0.93 compared to the non-ACS group (95% confidence interval [CI], 0.83–1.04, P = 0.1778). There was no statistically significant difference in stroke subtype distribution between the two groups (P = 0.2114).

Conclusions

These findings indicate that ACS itself is not associated with an increased risk of subsequent stroke.     

Dynamic Scapular Movement Analysis: Is It Feasible and Reliable in Stroke Patients during Arm Elevation?

Knowledge of three-dimensional scapular movements is essential to understand post-stroke shoulder pain. The goal of the present work is to determine the feasibility and the within and between session reliability of a movement protocol for three-dimensional scapular movement analysis in stroke patients with mild to moderate impairment, using an optoelectronic measurement system. Scapular kinematics of 10 stroke patients and 10 healthy controls was recorded on two occasions during active anteflexion and abduction from 0° to 60° and from 0° to 120°. All tasks were executed unilaterally and bilaterally. The protocol’s feasibility was first assessed, followed by within and between session reliability of scapular total range of motion (ROM), joint angles at start position and of angular waveforms. Additionally, measurement errors were calculated for all parameters. Results indicated that the protocol was generally feasible for this group of patients and assessors. Within session reliability was very good for all tasks. Between sessions, scapular angles at start position were measured reliably for most tasks, while scapular ROM was more reliable during the 120° tasks. In general, scapular angles showed higher reliability during anteflexion compared to abduction, especially for protraction. Scapular lateral rotations resulted in smallest measurement errors. This study indicates that scapular kinematics can be measured reliably and with precision within one measurement session. In case of multiple test sessions, further methodological optimization is required for this protocol to be suitable for clinical decision-making and evaluation of treatment efficacy.     

Digital Subtraction Angiography Imaging Characteristics of Patients with Extra–Intracranial Atherosclerosis and Its Relationship to Stroke

To investigate the angiographic characteristics and clinical features in patients with suspected extra–intracranial atherosclerosis in a large cohort of Chinese population. On the basis of digital subtraction angiography characteristics, pathological morphology of extra–intracranial atherosclerosis was divided into tortuosity, kinking, coiling, and stenosis in 2,218 individuals aged 45–89 years. The degree of stenosis was further divided into low-grade (<30 %), intermediate-grade (30–69 %), and high-grade stenosis (≥70 %). Clinical manifestations were divided into transient ischemic attack, cerebral infarction and cerebral hemorrhage. The prevalence of tortuosity and stenosis were significantly higher in the extracranial arterial system than that of intracranial arterial system. The prevalence of tortuosity and kinking were significantly higher on the left side than the right side. The prevalence of mild and moderate stenosis in the internal carotid artery was significantly higher in the left side than the right side. The incidence of cerebral infarction was significantly higher in the internal carotid arterial (ICA) system than the vertebrobasilar arterial (VBA) system. Tortuosity is a common carotid abnormality in the Chinese population. The prevalence of ICA tortuosity is higher than that of VBA. The incidence of cerebral infarction in each atherosclerosis group was significantly higher in ICA than that of VBA. The prevalence of stroke is higher in the ICA system than the VBA system. Kinkings and coilings may not have a clinical significance if these lesions are not associated with atheromatous plaques or carotid stenosis.     

Evidence that NF-κB and MAPK Signaling Promotes NLRP Inflammasome Activation in Neurons Following Ischemic Stroke

Multi-protein complexes, termed “inflammasomes,” are known to contribute to neuronal cell death and brain injury following ischemic stroke. Ischemic stroke increases the expression and activation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) Pyrin domain containing 1 and 3 (NLRP1 and NLRP3) inflammasome proteins and both interleukin (IL)-1β and IL-18 in neurons. In this study, we provide evidence that activation of either the NF-κB and MAPK signaling pathways was partly responsible for inducing the expression and activation of NLRP1 and NLRP3 inflammasome proteins and that these effects can be attenuated using pharmacological inhibitors of these two pathways in neurons and brain tissue under in vitro and in vivo ischemic conditions, respectively. Moreover, these findings provided supporting evidence that treatment with intravenous immunoglobulin (IVIg) preparation can reduce activation of the NF-κB and MAPK signaling pathways resulting in decreased expression and activation of NLRP1 and NLRP3 inflammasomes, as well as increasing expression of anti-apoptotic proteins, Bcl-2 and Bcl-xL, in primary cortical neurons and/or cerebral tissue under in vitro and in vivo ischemic conditions. In summary, these results provide compelling evidence that both the NF-κB and MAPK signaling pathways play a pivotal role in regulating the expression and activation of NLRP1 and NLRP3 inflammasomes in primary cortical neurons and brain tissue under ischemic conditions. In addition, treatment with IVIg preparation decreased the activation of the NF-κB and MAPK signaling pathways, and thus attenuated the expression and activation of NLRP1 and NLRP3 inflammasomes in primary cortical neurons under ischemic conditions. Hence, these findings suggest that therapeutic interventions that target inflammasome activation in neurons may provide new opportunities in the future treatment of ischemic stroke.     

Gingival Inflammation Associates with Stroke – A Role for Oral Health Personnel in Prevention: A Database Study

Objectives

Gingival inflammation is the physiological response to poor oral hygiene. If gingivitis is not resolved the response will become an established lesion.We studied whether gingivitis associates with elevated risk for stroke. The hypothesis was based on the periodontitis–atherosclerosis paradigm.

Methods

In our prospective cohort study from Sweden 1676 randomly selected subjects were followed up from 1985 to 2012. All subjects underwent clinical oral examination and answered a questionnaire assessing background variables such as socio-economic status and pack-years of smoking. Cases with stroke were recorded from the Center of Epidemiology, Swedish National Board of Health and Welfare, Sweden, and classified according to the WHO International Classification of Diseases. Unpaired t-test, chi-square tests, and multiple logistic regression analyses were used.

Results

Of the 1676 participants, 39 subjects (2.3%) had been diagnosed with stroke. There were significant differences between the patients with stroke and subjects without in pack-years of smoking (p = 0.01), prevalence of gingival inflammation (GI) (p = 0.03), and dental calculus (p = 0.017). In a multiple regression analysis the association between GI, confounders and stroke, GI showed odds ratio 2.20 (95% confidence interval 1.02–4.74) for stroke.

Conclusion

Our present findings showed that gingival inflammation clearly associated with stroke in this 26-year cohort study. The results emphasize the role of oral health personnel in prevention.