There is a continuous urgent need to explore the pathogenesis and biochemical changes within the infarcted area during acute ischemic stroke (IS). Matrix metalloproteinases (MMPs), prevailing extracellular endopeptideses, can digest proteins located extracellulary, e.g. collagen, proteoglycans, elastin or fibronectin. Among MMPs, gelatinases (MMP-2 and MMP-9) are the most investigated enzymes. Gelatinases possess the ability to active numerous pro-inflammatory agents as chemokine CXCL-8, interleukin 1β or tumor necrosis factor α. Moreover, due to digestion of collagen type IV (the component of basal membranes) and tight junction proteins (TJPs) they facilitate to cross the endothelium by leukocytes. Due to the significant role of gelatinases during brain ischemia, their selective inhibition seems to be an interesting kind of treatment of acute stroke. The synthetic inhibitors of gelatineses decrease the infarct volume in animal models of IS. In clinical practice statins, the lipid-lowering drugs possess the ability to inhibit the activity of MMP-9 during acute IS. This review briefly provides the most important information about the involvement of MMP-2 and MMP-9 in the pathogenesis of brain ischemia.
The prediction of outcome after ischemic stroke (IS) is currently based on indirect data from clinical and radiological evaluation. We evaluated the usefulness of serum Tau protein as possible prognostic markers for IS. Fifty-six patients with computed tomography-confirmed IS were enrolled. Blood samples were obtained on days 1, 3, 5, and 10 after stroke onset. Tau and S100BB serum levels were measured by commercially available enzyme-linked immunosorbent assay. Neurological deficits were quantified by the National Institute of Health Stroke Scale on days 1, 3, 5, and 10 of stroke. Functional disability was rated with the Barthel Index and Rankin Scale on days 1, 3, 5, and 10 and additionally 3 months after the stroke. Computed tomography scan was performed to calculate infarct volume on admission to hospital and on day 10 from the diagnosis of IS onset. Tau protein was detected in the serum of 47.8% patients with IS. Patients in whom Tau protein was detected in serum, when compared with patients without Tau protein, developed more severe neurological deficits, had worse functional status measured in the early and late phase of IS, and were found to have larger volume of infarction. However, Tau protein concentrations measured within the early phase of IS did not correlate with degrees of neurological deficit and disability in the early phase and also after 3 months of IS. Detection of Tau protein in the serum of patients with IS but not its concentration can be considered as a bad prognostic factor for the clinical outcome in early and late phase of IS.
Bilirubin (Bil) and uric acid (UA) are the endogenous antioxidant compounds possibly involved in the pathogenesis of ischemic stroke (IS). Our goal was to find the relationship between serum Bil and UA levels with clinical presentation and outcomes of patients suffering from IS. Forty-three patients (mean age: 71.9 years, +/- 12.1; women: 48.8%) with confirmed IS were enrolled. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) after 1, 3, 5, and 10 days and functional disability was assessed three months after stroke onset using the Barthel Index (BI). Serum Bil and UA levels were measured 1, 3, 5, and 10 days after stroke. The difference between NIHSS scores from days 1 and 10 (improvement ratio) inversely correlated with the average UA serum level (r = -0.48, p < .01) but not with the average Bil level. Negative correlations were observed between the BI measured three months after stroke compared to the average Bil serum level (r = -0.5, p < .01). However, no relationship between BI and UA level was observed. Our results indicated that Bil and UA levels are poor prognostic factors for ischemic stroke.
Objectives We investigated the influence of spinal cord stimulation (SCS) on IFN-γ, IL-1β, IL-6, TNF-α, IL-10, and TGF-β serum levels in failed back surgery syndrome (FBSS) patients. The study will try to give new insights into the mechanism of SCS action and the role of IFN-γ and other cytokines in neuropathic pain (NP) development. Materials and Methods Clinical and biochemical assessment was conducted in four groups of patients: group 0 consisted of 24 FBSS patients qualified to SCS therapy, group 1 included 17 patients who were one month after implantation, group 2 featured 12 patients who were 3 months after the implantation, and group C (the control group) with no NP. Clinical status was assessed with the use of Numeric Rating Scale (NRS), the Pain Rating Index of McGill Pain Questionnaire (SF-MPQ), the Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). The plasma concentrations of IFN-γ were ascertained by an immunoenzymatic method. Results We found a significant difference between the patients before SCS and controls' serum level of IFN-γ. Similarly, a significantly higher level of TNF-α and significantly lower level of IL-10 in FBSS patients than controls were observed. The significant differences were not observed between SCS patients 3 months after the procedure and controls' serum level of IFN-γ and other cytokines. We noticed a positive correlation between IFN-γ concentration with NRS back value before SCS and positive correlation between IFN-γ concentration after SCS with NRS leg value before SCS. Higher IFN-γ concentrations accompanied higher NRS values. Levels of TGF-β and IL-10 may correlate with physical ability and depressive behavior. Conclusions SCS did not influence serum cytokine levels significantly. Serum concentration of IFN-γ may be recognized as an occasional pain factor because of its significantly higher level in FBSS patients versus controls and higher IFN-γ value accompanying higher pain intensity.
Objectives. To compare the viability of the numerical rating scale (NRS) and the visual analogue scale (VAS) as a pain assessment tools among a large cohort of patients who underwent microdiscectomy. Summary of Background Data. The pain intensity (PI) reduction is a parameter of surgical treatment efficacy. The two most commonly used scales of PI are NRS and VAS. Many studies have shown strong similarities between those two scales, but the direct interchange is difficult. Methods. Patients, who underwent microdiscectomy, were prospectively enrolled into the study and assessed using VAS and NRS for the back (NRS-B) and the leg (NRS-L), Short Form of McGill Pain Questionnaire (SF-MPQ) included Pain Rating Index (PRI) and Oswestry Disability Index (ODI) 1 day before and 1 month and 3 months after the procedure. Results. 131 patients were included in the study. NRS-L, NRS-B, VAS, and ODI were significantly lower ( p < 0.001 ) 1 month after microdiscectomy. NRS-L and NRS-B ratings remained at a similar level while VAS and ODI decreased after 3 months. The rate of decline of PI measured by NRS-L correlated statistically significant (rs = 0.366; p < 0.001 ) with ODI 1 month after surgery. Before surgery, the most significant correlation was found between ODI and NRS-L (rs = 0.494; p < 0.001 ), the lowest with NRS-B (rs = 0.319; p < 0.001 ). 3 months after surgery, there was higher correlations between ODI and VAS (rs = 0.634) than NRS-L (rs = 0.265). PRI correlated significantly ( p < 0.001 ) and more stronger with VAS than with NRS-L and NRS-B in every points of assessment. Conclusion. The results showed that PI measurements by NRS-L/NRS-B and VAS mutually correlate and impair functionality evaluated by ODI (convergent validity) but in different modes (differential validity). NRS and VAS are not parallel scales and assess different aspects of pain. The measurement of NRS-L 1 month after microdiscectomy seems to give quick insight into the effectiveness of the procedure.
High serum albumin levels during ischemic stroke (IS) decrease the risk of a poor outcome. This study aimed to determine whether serum albumin levels within the first days after IS correlate with radiological and biochemical markers of brain tissue damage. Fifty-six IS patients were enrolled into the study. Neurological examinations were based on the National Institute of Health Stroke Scale. Serum albumin levels and S100BB were evaluated using commercially available ELISA kits. The albumin decrease index (ADI) was calculated as the difference between serum albumin levels measured on days 1 and 10 of IS. All parameters were estimated on the 1st, 3rd, 5th, and 10th days of IS, and the volume of ischemic focus was measured on the 10th day. Mean serum albumin levels were decreased during acute IS. There were correlations between the ADI and mean S100BB serum levels (r = 0.36, p < 0.05), the volume of ischemic focus (r = 0.39, p < 0.05), and the patients’ neurological state when measured on day 10 of IS (r = 0.59, p < 0.001). A decrease in serum albumin levels during the acute phase of IS corresponds to a worse neurological state as a result of a large ischemic focus with intense catabolic processes.
One of the most significant side effects during recombinant tissue plasminogen activator (rtPA) for acute stroke treatment is intracranial bleeding. Gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] are one of the agents involved in the blood-brain barrier destruction resulting in secondary bleeding into the ischemic area during stroke. Previous papers revealed that patients with high baseline MMP-9 serum level have higher risk of intracranial bleeding after thrombolytic therapy. Our objective was to evaluate rtPA influence on serum MMP-2 and MMP-9 activities in vitro. Nine sera obtained from healthy donors were applied for experiment. The commercially available rtPA (Actylise) were diluted with included solvent and additionally with phosphate-buffered saline (PBS) to get concentrations: 2, 4, 8, and 16 μg/ml. Next, 100 μl of serum was mixed with equal proportion with different concentrations of rtPA to obtain final rtPA concentrations: 1, 2, 4, and 8 μg/ml. The sera together with rtPA were incubated for 1 or 2 hours at 37 °C. The activity of gelatinases was estimated with zymography. The activities of MMP-9 (92 kDa) and MMP-2 (72 kDa) were increased by incubation with rtPA in a dose-dependent manner. Simultaneously, the activity of band at 200 kDa (MMP-9/MMP-9 homodimer) was decreased. The activity of gelatinases incubated for 2 hours was elevated in comparison with 1-hour incubation; however, the increase was observed even for sample without rtPA. In conclusion, this study showed that rtPA can increase the biological activity of MMP-2 and MMP-9 on posttranslational level.
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