The aim of this study was to investigate the exogenous agmatine influence on nitrosative and oxidative stress parameters in acute phase of multiple sclerosis (MS) experimental model, experimental autoimmune encephalomyelitis (EAE). EAE was induced by subcutaneous injection of myelin basic protein (50 μg per animal). Sprague-Dawley rats were divided into five groups: I group -(CG), treated by PBS (i.p.), II group -(EAE), III group -(CFA), treated with Complete Freund's adjuvant (0.2 ml subcutaneously), IV group -(EAE+AGM), treated by agmatine (75 mg/kg bw i.p.) upon EAE induction and V group -(AGM), received only agmatine in the same dose. The animals were treated every day during experimentfrom day 0 to 15, and clinically scored every day. They were sacrificed on day 16 from MBP application. NO 2 +NO 3 , S-nitrosothiols (RSNO), malondyaldehide (MDA) and reduced glutathione (GSH) concentrations and superoxide dismutase (SOD) activity were determined in rat whole encephalitic mass (WEM) and cerebellum homogenates.Agmatine exerted strong protective effects on EAE clinical symptoms (p<0.05). In EAE brain homogenates, NO 2 +NO 3 , RSNO and MDA concentrations were increased compared to CG values. Agmatine treatment diminished NO 2 +NO 3 , RSNO and MDA levels in EAE animals (p<0.05). In EAE rats, GSH level and SOD activity were decreased compared to CG values, but agmatine treatment increased both parameters compared to EAE untreated animals (p<0.05). Immunohistochemical staining supported the clinical and biochemical findings in all groups.The CNS changes in EAE are successfully supressed by agmatine application, which could be the the new aspect of the neuroprotective effects of agmatine.
Summary: Nitric oxide (NO) is an important signalling molecule in a variety of physiological processes. NO, a gas, is produced from L-arginine by different isoforms of the nitric oxide synthase and serves as mediator in important physiological functions, such as promoting vasodilation of blood vessels and mediating communication between nervous system cells. Contradictory to its physiologic actions, free radical activity of NO can cause cellular damage by the induction of nitrosative stress with significant implications on nervous system diseases. Although the mechanism of NOmediated neurodegeneration still remains unclear, numerous studies suggest its crucial role in modification of protein functions by nitrosylation and nitro-tyrosination. NO contributes to glutamate excitotoxicity, participates in organelle fragmentation, inhibits mitochondrial respiratory complexes and mobilizes zinc from the internal stores. Recently, NO has been emerged as a mediator of epigenetic gene expression and chromatin changes. Besides, NO is a key mediator in the regulation of inflammatory and immune response of the central nervous system. It is involved in down regulation of several aspects of CNS inflammation, but also has a dual role in that it is required for inflammation in some situations.
Keywords: nitric oxide, nitrosative stress, protein S-nitrosylation, neuroinflammation, neurodegenerationKratak sadr`aj: Azot monoksid je va`an signalni molekul u brojnim fiziolo{kim procesima. Ovaj gas se stvara iz L-arginina dejstvom tri izoforme azot monoksid sintaze i medijator je va`nih fiziolo{kih funkcija, kao {to su posredovanje u regulaciji tonusa krvnih sudova i komunikaciji }elija nervnog sistema. Nasuprot ovim ulogama, kao slobodni radikal, NO mo`e izazvati }elijsko o{te}enje indukcijom nitrozativnog stresa, {to ima zna~ajne implikacije u bolestima nervnog sistema. Mada je mehanizam neurodegeneracije posredovane azot monoksidom jo{ uvek nerazja{njen, brojne studije ukazu ju na njegovu klju~nu ulogu u modifikaciji funkcije proteina kroz procese S-nitrozilacije i nitrovanja tirozina. On doprinosi glutamatnoj ekscitotoksi~nosti, u~estvuje u fragmentaciji organela, inhibi{e mitohondrijalne respiratorne komplekse i mobili{e cink iz unutra{njih depoa. Nedavno je ukazano da mo`e biti medijator epigenetske genske ekspresije i promena hromatina. Pored toga, NO je klju~ni posrednik u regulaciji inflamatornog i imunog odgovora CNS. On u~estvuje u nishodnoj regulaciji nekoliko aspekata inflamacije CNS, ali tako|e ispoljava dualisti~ke efekte u uslovima inflamacije.
The aim of the paper was to identify the correlation between the parameters of hospital admission and clinical outcome in nontraumatic intracerebral hemorrhage (ICH) patients younger than 65 years, who were not surgically but conservatively treated only. The analyzed data was collected from the medical records of 341 consecutive patients who suffered a nontraumatic ICH and were conservatively treated. Demographics, medical history, clinical, radiological and biochemical variables on hospital admission and other relevant findings were analyzed in reference to functional outcome of non-traumatic ICH (measured on discharge from hospital). The following parameters were recognized as the predictors of fatal clinical outcome: lower values of GCS (OR 0.686, p = 0.023), high values of NIHSS (OR 1.258, p < 0.001), body temperature on hospital admission (OR 1.896, p = 0.034), absence of headache in ICH clinical presentation (OR 0.298, p = 0.012) as well as the sedimentation rate (OR 1.028, p = 0.045). The predictors of good clinical outcome after ICH were as follows: high values of GCS (OR 1.876, p = 0.032), lower values of NIHSS (OR 0.841, p = 0.002) and persistence of headache in ICH clinical presentation (OR 5.115, p = 0.001). Recognition of predictive factors could help to identify the patients at high risk of ICH progression and can help in the selection of pathogenetic therapy that could minimize the possibility of ICH progression.
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