Przemysław Nowacki

Clinical Evidence That Very Small Embryonic-Like Stem Cells Are Mobilized Into Peripheral Blood in Patients After Stroke

Background and Purpose— In a murine model of stroke, we identified a population of very small embryonic-like (VSEL) stem cells (SCs) in adult murine bone marrow that could be mobilized into peripheral blood (PB). This raised the question of whether a similar population of cells is mobilized in human stroke patients. Methods— We evaluated a number of cells that corresponded to VSEL SCs in the PB of 44 stroke patients and 22 age-matched controls. After each patient’s stroke, PB samples were harvested during the first 24 hours, on day +3, and on day +7 and then compared with normal controls. The circulating human cells with the phenotype of VSEL SCs were evaluated in PB by real-time quantitative polymerase chain reaction, fluorescence-activated cell sorting analysis, and direct immunofluorescence staining. In parallel, we also measured the serum concentration of stromal derived factor-1 by ELISA. Results— In stroke patients, we found an increase in the number of circulating cells expressing SC-associated antigens, such as CD133, CD34, and CXCR4. More important, we found an increase in the number of circulating primitive cells expressing the VSEL phenotype (CXCR4+lin-CD45- small cells), mRNA for Octamer-4 and Nanog, and Octamer-4 protein. All changes were accompanied by an increased serum concentration of stromal derived factor-1. Additionally, we found a positive correlation between stroke extensiveness, stromal derived factor-1 concentration in serum, and the number of CXCR4+ VSEL SCs circulating in the PB. Conclusions— We conclude that stroke triggers the mobilization of CXCR4+ VSEL SCs that have potential prognostic value in stroke patients. However, the potential role of these mobilized cells in brain regeneration requires further study.

Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism.

Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation.

Increased circulating endothelial progenitor cells in patients with haemorrhagic and ischaemic stroke: The role of Endothelin-1

Ischaemic stroke induces endothelial progenitor cell (EPC) mobilisation from bone marrow into peripheral blood. Circulating EPCs play an important role in post-injury regeneration of vasculature, whereas endothelial cells (ECs) have been shown to reflect endothelial damage and may be responsible for increased Endothelin-1 (ET-1) expression. We investigated herein the association between numbers of circulating ECs and EPCs, the levels of soluble factors regulating their migration and function, and the clinical outcome in patients with haemorrhagic (HS) or ischaemic stroke (IS). Sixteen patients with HS and eighteen with IS were assessed during the first 24h, day 3, and day 7 after stroke and compared them with twenty-three control subjects. We found elevated EPC and EC concentrations using flow cytometry and increase in VEGF, SDF-1, HGF, and ET-1 plasma levels by ELISA in the HS patients, while ET-1 mRNA expression in peripheral blood cells was elevated in the IS patients. Significant correlations were observed between EPCs or ECs and Big ET-1 protein or mRNA levels in HS but not in the IS patients. We suggest that ET-1 may play a role in pathophysiology of stroke and subsequent EPC mobilisation; however, further studies aimed at the precise elucidation of this issue are required.

Can we talk about CD4+CD28- lymphocytes as a risk factor for ischemic stroke?

Background: CD4+CD28– lymphocytes are implicated in the destabilization of atheromatous plaque, leading to acute coronary episodes. One may ask whether these cells play a similar role in ischemic stroke pathogenesis with an atherosclerotic background. Methods: Flow cytometry was applied to determine the percentage of CD4+CD28– lymphocytes in the peripheral blood of patients during the acute phase of their first ischemic stroke (group I) and in patients without a history of stroke but with two of the most important risk factors (hypertension, diabetes) for atherosclerosis-related ischemic stroke (group II). The results were compared with healthy controls. Results: The median percentages of CD4+CD28– lymphocytes in groups I and II did not differ significantly, but for each of these groups the percentage was higher than in the control group. The time of blood sampling from onset of stroke, presence of the ischemic focus in the CT brain scan and severity of neurological deficits did not correlate with the percentage of CD4+CD28– lymphocytes. Conclusions: We conclude that CD4+CD28– lymphocytes are implicated in mechanisms enhancing the risk of acute ischemic stroke and not a consequence of stroke.

Patients’ and Bystanders’ Awareness of Stroke and Pre-Hospital Delay after Stroke Onset: Perspectives for Thrombolysis in West Pomerania Province, Poland

Objective: Thrombolysis is a time-dependent therapy. It is therefore very important how fast stroke patients can reach hospital. The present study was designed to assess which proportion of patients with stroke (from the population of Szczecin, the capital of West Pomerania Province, Poland) reaches hospital within the recommended time from the thrombolytic therapy point of view. The purpose of our study was also to elucidate which factors can influence the time before the ambulance service is called. Patients and Methods: The study involved 1,015 patients with stroke admitted to the Emergency Department of the University Hospital, Szczecin. Results: 235 patients (23.1%) were admitted to the hospital within the appropriate period for thrombolytic therapy. Hospital arrival time was significantly earlier in older patients and in patients with severer neurological deficits. We also observed a tendency for faster hospitalization of women, the highly educated, and patients regularly using antiplatelet drugs for cardiovascular disease prevention. Conclusions: The percentage of stroke patients hospitalized within 2 h after stroke onset should be increased. The most susceptible subpopulations in our country seem to be older patients, the highly educated and patients regularly using antiplatelet drugs for cardiovascular disease prevention.

Normalization of the psychometric hepatic encephalopathy score in Polish population. A prospective, quantified electroencephalography study

The psychometric hepatic encephalopathy score (PHES) is recommended as a gold standard in evaluation of minimal hepatic encephalopathy (HE). Normative databases have been collected in few countries, clearly showing differences among studied groups. Thus, the standardization of PHES for selected populations remains necessary.

Mini-Mental State Examination in patients with hepatic encephalopathy and liver cirrhosis: a prospective, quantified electroencephalography study

BackgroundMini-Mental State Examination (MMSE) is one of the most commonly used methods in the assessment of cognitive mental status. MMSE has been used in hepatology but its usefulness in the evaluation of hepatic encephalopathy (HE) has never been properly assessed. The aim of the study was to investigate the value of MMSE in detection of HE in patients with cirrhosis.MethodsOne hundred and one consecutive patients with liver cirrhosis underwent neurological examination, MMSE and electroencephalography (EEG). Spectral analysis of EEG was done with calculation of mean dominant frequency (MDF) and relative power of delta, theta, alpha and beta rhythms. Minimal HE was diagnosed in patients with normal neurological status and alterations in spectral EEG. Statistical analysis included Fisher’s exact and Anova analysis. Categorical data were compared using Levene’s test for equality of variances. Correlation-coefficient analysis was performed by the Pearson’s r or Z-test, as needed. Tests performance was assessed by the calculating the area under the ROC curve (AUC) and evaluating its difference from reference area (AUC=0.5). A p value <0.05 was considered statistically significant.ResultsOvert HE was identified in 49 (48.5%) and minimal HE in 22 (21.8%) patients. Although there were significant correlations between both severity of liver disease (Child-Pugh classification), overt HE (West-Haven criteria) and various MMSE items, MDF showed no correlation with any of MMSE items as well as MMSE summary score. MMSE (score and items) did not discriminate patients without HE and minimal HE. The only significant differences between patients without HE and with overt HE were seen in respect of MMSE score (p<0.02), orientation to place (p<0.003), repetition (p<0.01) and complex commands-understanding (p<0.02). Test performance analysis has shown that MMSE has no value as a prediction method in determining minimal HE and in respect of overt HE has a sensitivity of 63% and specificity of 52% by a cut-off level at 27.5 points to diagnose overt HE.ConclusionsIn conclusion, although MMSE score and single items are altered in patients with overt HE, MMSE has no value in the assessment of minimal HE. Because MMSE could be impaired in several cognitive dysfunctions, more specific test should be used for measuring HE.

Potential role of statins in the intracerebral hemorrhage and subarachnoid hemorrhage

Statins are used in primary and secondary prevention of cardiovascular episodes. Most of recent studies regard ischemic stroke. There are more emerging results of studies suggesting usefulness of these drugs in the other types of stroke e.g. intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Searching for new methods of treatment is important, because both ICH and SAH lead to poor prognosis and severe psychomotor disability. The unquestionable role of inflammatory factors in the pathogenesis of these disorders justifies considering statin treatment. Previous results are contradictory, thus in present study we review results of studies and try to explain the potential pathomechanism of statin use in hemorrhagic strokes.

Anti-oxLDL antibodies are clinically insignificant for stroke patients.

Abstract Objectives: The question about anti-oxidized low-density lipoprotein antibodies (anti-oxLDL Abs) involvement in the pathogenesis of atherosclerosis-related ischemic stroke is still open. The aim of this study was to determine how anti-oxLDL Abs are involved in the pathogenesis of atherosclerosis-related ischemic stroke and identify the main risk factors for stroke, such as arterial hypertension, diabetes mellitus type 2, dyslipidemia, and atherosclerotic changes in the common and internal carotid arteries. Material and Methods: A total of 40 stroke patients and 25 age- and sex-matched healthy individuals were included in the study. For each subject, IgG anti-oxLDL Abs expression in peripheral blood was assessed and analyzed in relation to clinical data, carotid Doppler ultrasonography results, and results of peripheral blood laboratory tests, including inflammatory parameters and lipid profile. Results: The blood level of assessed antibodies was significantly higher in stroke patients than in control group. It did not relate to stroke severity and stroke outcome. The relationship between anti-oxLDL Abs and carotid plaques hyperechogenicity was observed. The antibodies concentration was significantly higher in patients with diabetes mellitus type 2 and also positively correlated with C-reactive protein blood level. However, multiple regression method did not confirm their independent influence. Discussion: Patients with atherogenic ischemic stroke may have significantly higher anti-oxLDL Abs concentrations. This should be interpreted as an attempt to limit the consequences of oxLDL production; however, this phenomenon does not seem to protect patients against cerebrovascular events.

In patients with liver cirrhosis, proinflammatory interleukins correlate with health-related quality of life irrespective of minimal hepatic encephalopathy.

Background Liver cirrhosis is associated with latent systemic inflammatory response syndrome as evidenced by elevated levels of proinflammatory cytokines. It has been proposed that inflammatory mediators play a role in the pathogenesis of minimal and overt hepatic encephalopathy (HE); hence, they may also have an effect on health-related quality of life (HRQL). The aim of this study was to investigate the relationship between serum levels of interleukin-1&bgr; (IL-1&bgr;), IL-6, and IL-18 and the occurrence of minimal HE and HRQL. Methods Forty-two consecutive patients with liver cirrhosis were prospectively enrolled to the study. Minimal HE was detected by the Psychometric Hepatic Encephalopathy Score (PHES) and critical flicker frequency. HRQL was assessed with Chronic Liver Disease Questionnaire and 36-Item Short Form Health Survey (SF-36) questionnaires. The interleukins studied were determined using colorimetric sandwich enzyme-linked immunosorbent assay. Results Serum levels of interleukins correlated with liver dysfunction, but did not discriminate patients with minimal HE from those with overt or absent HE. IL-1&bgr; and IL-6 showed significant correlations with PHES, but showed no relationship with critical flicker frequency. Serum IL-6 and IL-18 correlated with both physical-related general health and mental component summary evaluated by the SF-36 questionnaire. Conclusion This study shows that chronic inflammation plays a role in impaired HRQL in patients with cirrhosis irrespective of minimal HE.