Joanna Bielewicz

The significance of matrix metalloproteinase (MMP)-2 and MMP-9 in the ischemic stroke

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.

SERUM BILIRUBIN AND URIC ACID LEVELS AS THE BAD PROGNOSTIC FACTORS IN THE ISCHEMIC STROKE

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.

Matrix metalloproteinase-9 contributes to the increase of tau protein in serum during acute ischemic stroke

Previous studies indicate that tau protein, a marker of damage to neurons, is present in the serum of healthy patients at a concentration approximately 40 percent that of patients with ischemic stroke We assumed that increased serum activity of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9) can influence the level of tau protein in serum, probably due to disruption of the blood-brain barrier. We obtained blood sera from 31 patients admitted within the first 24 hours of ischemic stroke on days 1, 5 and 10, following the onset of stroke. Tau protein was detected in the serum of 12 patients (38.7 percent). The highest MMP-9 activity was recorded on day 5 (p < 0.05). Serum gelatinase activity did not differ between tau protein-positive or -negative individuals. However, a high degree of correlation between mean MMP-9 activity and the maximum tau protein level was observed for patients with detectable tau protein (r = 0.71, p = 0.009). Our study suggests that MMP-9 can increase the tau protein level in the sera of patients during acute ischemic stroke.

The effect of recombinant tissue plasminogen activator on MMP-2 and MMP-9 activities in vitro

Abstract 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.

CT volume/density ratio as the marker of ischaemic brain injury

Kurzepa J, Bielewicz J, Czekajska‐Chehab E, Kurzepa J, Bartosik‐Psujek H, Grabarska A, Stelmasiak Z. CT volume/density ratio as the marker of ischaemic brain injury.
Acta Neurol Scand: 2011: 123: 310–315.
© 2010 John Wiley & Sons A/S.

Wernicke-Korsakoff syndrome as a rare phenotype of sporadic Creutzfeldt-Jakob disease

ABSTRACT We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66-year-old female complained of dizziness and imbalance which mostly occurred while walking. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory disturbances with confabulations. The disturbances increased during the course of the disease, which led to the death of the patient four months after the appearance of the signs. The patient was finally diagnosed with sCJD disease. The most useful ancillary examination results supporting sCJD diagnosis were brain diffusion DWI MRI (diffusion weighted magnetic resonance imaging) and the presence of 14–3-3 protein in CSF (cerebrospinal fluid). Since that manifestation of sCJD is very unique other causes should be taken into consideration while making a final diagnosis.

Correlation between CH2DS2-VASc Score and Serum Leptin Levels in Cardioembolic Stroke Patients: The Impact of Metabolic Syndrome

Objective To determine adipokines levels in patients with different etiologic subtypes of acute ischemic stroke (AIS) and metabolic syndrome (MetS) status. Methods Serum adiponectin, leptin, and resistin levels were determined by ELISA in 99 AIS patients and 59 stroke-free control group subjects. Stroke patients were grouped based on MetS, modified TOAST classification, and CHA2DS2-VASc scale in case of cardioembolic stroke following atrial fibrillation. Results No differences were found in all adipokine serum levels between AIS patients and appropriately matched control group. MetS-AIS patients had significantly higher leptin levels (22.71 ± 19.01 ng/ml versus 8.95 ± 9.22 ng/ml, p < 0.001) and lower adiponectin levels (10.71 ± 8.59 ng/ml versus 14.93 ± 10.95 ng/ml, p < 0.05) than non-MetS-AIS patients. In patients with cardioembolic stroke, leptin levels were significantly higher than in remaining stroke cases (19.57 ± 20.53 ng/ml versus 13.17 ± 12.36 ng/ml, p < 0.05) and CHA2DS2-VASc score positively correlated with leptin levels only (p < 0.001). Analysis of individual components of CHA2DS2-VASc score showed that hypertension, female gender, and diabetes had greatest impact on elevated serum leptin level. Conclusion This pilot study revealed that leptin could be a potential biomarker for risk stratification of cardioembolic stroke in MetS patients and that heterogeneity of stroke subtypes should be considered for more refined and precise clinical stroke studies.

Can CRP affect the blood-brain barrier during acute ischemic stroke?

Abstract Introduction. Ischemic strokes (IS) are one of the main causes of death and disabilities around the globe. Therefore, there is a huge need for researching the pathogenesis of IS. The C-reactive protein (CRP) plays a role during inflammatory processes. Results of some studies conducted on animal models indicate that CRP affects the blood-brain barrier (BBB) stability during IS. The presence of S100BB protein can be considered as an indication of BBB injury. Aim. The purpose of this study was to discover the relationship between CRP and S100BB protein. Material and methods. The study looked at fifty four IS patients, with the disease confirmed by computer tomography (CT). The clinical status was evaluated on the 1st, 3rd, 5th, 10th day and 3 months following the onset of IS. Neurological status was estimated using the National Institute of Health Stroke Scale (NIHSS). Patients’ disability level was determined, using Modified Rankin Scale (mRS) and Barthel Index (BI). The volume of ischemic focus was calculated on the 10th day after the stroke, using CT. The levels of CRP and S100BB were evaluated on 1st, 3rd, 5th and 10th day after the stroke onset with usage of ELISA method. Results. The mean level of CRP and its concentration on the 1st, 3rd, 5th and 10th day directly correlates with a deteriorated clinical status, as measured with the use of NIHSS, BI and mRS on day 10 and 3 months after the onset of IS. We found a correlation with the mean CRP level and bigger volume of ischemic injury. The mean CRP level correlated with the mean level of S100BB protein. In the group of patients with low CRP (0.51-24.68 mg/mL) the level of S100BB and the volume of ischemic focus were lower than in the group with a high level of CRP (24.69-209 mg/mL). Conclusions. CRP can be considered as a predictor of a worse clinical outcome after stroke. The relationship between CRP and S100BB protein can suggest the active role of CRP during IS