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Losy J. and Bernat R.: Catecholamines in the rat brain during hypoglycemic convulsions and coma. Acta physiol, pol. 1989,40 (5-6): 479-485. The purpose of the study was to investigate the relation between the catecholamines: noradrenaline and dopamine in the rat brain on one hand and hypoglycemic convulsions and coma on the other. Concentrations of naradrenaline in the hypothalamus, brain stem and cerebral cortex were decreased during hypoglycemic convulsions and were lower during coma than those during convulsions. Dopamine concentration in the striatum was decreased during convulsions and coma. It was shown that the decrease in concentration of catecholamines was a result of hypoglycemia but not of insulin action itself. Clonidine-α₂ agonist accelerated occurrence and prolonged duration of hypoglycemic convulsions. Haloperidol-dopamine receptor blocker had no effect on the time of occurrence or duration of convulsions and coma. The results indicate that noradrenaline may exert an inhibitory influence on hypoglycemic convulsions, No evidence has been provided to support involvement of dopamine in the control of hypoglycemic convulsions and coma.
Stroke-induced inflammatory reaction leads to the accumulation of leukocytes in the brain ischaemic region, where they exert a detrimental effect - promotion and extension of cerebral damage. Intracerebral infiltration of peripheral blood leukocytes requires prior endothelial-leukocyte interactions that are mediated by such cell surface proteins as adhesion molecules. Among adhesion molecules, it is the immunoglobulin gene superfamily (IgSF) that is responsible for strong attachment and transendothelial migration of leukocytes. The principal members of IgSF are: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1). In this review the following issues were described and discussed: an increased expression of ICAM-1 and VCAM-1 in ischaemic brain as well as a detection of their soluble(s) forms in sera of stroke victims. The presented data suggest the involvement of both ICAM-1 and VCAM-1 in the sequence and timing of the infiltration of leukocytes into the brain ischaemic zone after stroke. They have also revealed changes in serum concentrations of sICAM-1 and sVCAM-1 that are characteristic for stroke. Recently, increase in sPECAM-1 levels in serum and cerebrospinal fluid (CSF) has been shown within 24 h of the onset of stroke, having indirectly suggested involvement of the molecule in the inflammatory events during the early phase of stroke.
Stroke-induced inflammatory reaction, which leads to invasion of leukocytes into the evolving brain infarct, seems to play a key role in the deterioration of brain ischaemic impairment. We have studied CSF and serum levels of tumour necrosis factor-alpha (TNF-alpha), the potent proinflammatory cytokine, and peripheral white blood cells (WBC) counts in patients within the first 24 hours of ischaemic stroke. TNF-alpha levels in CSF and serum as well as WBC counts were increased. There was no correlation between TNF-alpha levels either in CSF and serum or in WBC counts. The results of our study suggest that increased CSF TNF-alpha levels may represent acute intracerebral inflammation in stroke, whereas elevated levels of TNF-alpha in serum may reflect the peripheral proinflammatory state as well as stroke-induced systemic inflammatory reaction. Increased CSF and serum TNF-alpha levels do not correlate with the elevation of WBC counts, suggesting that TNF-alpha overexpression observed in early phase of stroke is not dependent on increased total number of peripheral leukocytes.
β-2 Microglobulin (β2M) is a low molecular weight protein located extracellularly and associated with class 1 antigens of the major histocompatibility complex and is considered a marker for disease activity in immune disorders. Cladribine (2-chloro-2-deoxyadenosine, 2-CDA) is a potent lymphocytotoxic agent under investigation in the treatment in MS patients. As β2M levels may indicate inflammatory events in CNS we determined CSF-β2M and serum β2M levels in patients with relapsing-remitting MS before and after cladribine treatment as well as in a control group. There was a significant β2M decrease in sera but not in CSF in MS patients after the cladribine treatment, associated with a slight but significant clinical improvement measured by Kurtzke’s Expanded Disability Status Scale. We also found a significant decrease in sICAM-1 level in CSF but not in sera in MS patients. The data support a role of cladribine in MS therapy and deliver new information on cladribine immunological effects in MS patients.
Introduction: Migraine is a known risk factor for ischemic stroke. Recent studies have shown endothelial dysfunction in migraine patients. The aim of this study was to examine the levels of circulating Vascular Endothelial Growth Factor (VEGF) during interictal period. Material and methods: We included in the study 52 migraineurs (aged 37.9 ± 9.6 years). All patients satisfi ed criteria of IHS for the diagnosis of migraine. The control group was represented by 34 healthy subjects (aged 28.9 ±7.0 years). Serum VEGF, Macrophage Infl ammatory Protein-1 (MIP-1) and tumor necrosis factor (TNF) were analyze by means of ELISA. Results: The level of circulating VEGF was decreased (<0.05) during interictal period of migraine patients (281.53 ± 180.37 pg/ml) comparing to controls (441.80 ± 295.93 pg/ml). There were no differences (P>0.05) between TNF concentration in migraineurs and controls (median, min.ñmax.: 2.04; 0.49ñ18.6 and 2.14; 0.49ñ8.97, respectively). Similarly, serum MIP-1 did not showed differences (P>0.05) between both groups (migraineurs: 0.0; 0.0ñ285.25 and controls: 0.0; 0.0ñ333.54 pg/ml). Serum VEGF correlated with MIP-1 (rS=0.7684, P<0.05) and TNF level (rS=0.4791, P<0.05). Conclusion: Migraineurs have decreased serum VEGF concentration, which may be related endothelial dysfunction and responsible for increased risk of stroke. Both TNF and MIP may be involved in regulatory processes of VEGF production.
Chemokines may play a role in the pathogenesis of multiple sclerosis (MS), facilitating the traffi cking of immune cells across the blood-brain barrier. Interferon-inducible T cell alpha chemoattractant (CXCL11) recruits activated Th1 cells to sites of infl ammation. We have estimated the levels of CXCL11 chemokine and IL-18 also known as IFN-gamma inducing factor in sera of 30 relapsingremitting MS patients during relapse, both before and after methylprednisolone (MP) treatment and compared the results with those in control group. The serum CXCL11 and IL-18 concentrations were measured by the ELISA method. The serum levels of CXCL11 were detectable in 23 relapsing-remitting MS patients. The levels were signifi cantly higher in sera of studied patients before (55.4 ± 63.1 pg/ml) and after steroid therapy (40.7 ± 43.2 pg/ml) in comparison with control group (17 ± 18.3 pg/ml, P=0.002). The serum levels of CXCL11 before and after MP treatment did not differ signifi cantly. The levels of IL-18 were detectable in the sera of all studied MS patients. The serum concentration of IL-18 in relapsing-remitting MS patients before MP therapy was 246.6 ± 143.5 pg/ml and was signifi cantly higher than the level of IL-18 in healthy controls (171.06 ± 56.8 pg/ml, P=0.008). IL-18 levels in the sera of MS patients after steroid therapy was 258.76 ± 292.5 pg/ml and was higher than that in the control group (P=0.006) but did not differ signifi cantly from the serum concentration of IL-18 in the same patients before the onset of MP treatment. The results suggest involvement of CXCL11 and IL-18 in immunopathogenesis of MS.
The acute phase response follows tissue injury and contributes to its exacerbation with pro-inflammatory and pro-thrombotic mechanisms. Acute phase proteins promote erythrocyte aggregation and falling, with the result that the erythrocyte sedimentation rate (ESR) is a measure of the acute phase response. As the acute phase response accompanies ischaemic brain damage, we studied ESR values in patients within the first 24 hours of ischaemic stroke and evaluated whether these values may be related to the volume of anatomically relevant single hemispheric brain computed tomography (CT) areas observed at the same period, indicating early stroke-related cerebral changes. We observed an increase in ESR in stroke patients and a positive correlation between the ESR values and the volume of early brain CT hypodense areas. The results suggest that elevation in ESR values is observed soon after a stroke and may reflect the relationship between the degree of acute phase response in the early phase of ischaemic stroke and the extent of local brain damage.
The examination of oligoclonal bands (OCB) in cerebrospinal fl uid (CSF) is important for the diagnosis of multiple sclerosis, however the correlation between quality, number and disease progression is uncertain. The aim of this study was to test the automatic system, for detection and identifi cation of OCB. The patterns of OCB, obtained from isoelectrofocusing of CSF proteins, were scanned with the use of fl atbed scanner. Next, for each of the scanned images, the selected features of the pattern were extracted by the means of the image processing algorithms, and arranged into the feature vector. That created the ìsignatureî of the image that was subsequently analyzed by classifi er based on the Artifi cial Neural Networksí. The result was the positive (P), negative (N) or ìuncertainî (U) classifi cation of the bandsí pattern. We have used database of the 225 samples, manually classifi ed by the expert, that formed the training set for the classifi er with the equal number of positive and negative results. Among 20 samples (10P/10N) used in the testing phase of the system 17 were classifi ed correctly, 3 were ìuncertainî, no false results was obtained. The system is implemented in the MATLAB environment. The future work focus on designing the system that would be able not only to classify the OCB patterns, but also to possibly cluster the images into the groups with common parameters.
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