[The novel views on the patomechanism of ischemic stroke]. / Nowe poglady na patomechanizm udaru niedokrwiennego mózgu.

Stroke is the third cause of death and the first cause of handicap. Current knowledge about stroke allows to apply the effective methods of treatment or prophylaxis. Eighteen five percent of all strokes are ischemic (IS), 15% are haemmorrhagic (HS). Unequal oxygen supply and the changes occurring in the macro and microcirculation results in the division of ischemic focus into the two areas; central core with an irreversible destruction of brain cells and penumbra, "semi-shadow area" around the core. The insufficient blood flow within the penumbra manifests the clinical symptoms of IS however the changes are reversible after the restoration of the correct circulation. We assumed five pathways leading to neurons' death: excitotoxicity and ionic imbalance, oxidative stress, inflamamation, peri-infract depolarization and apoptosis. This review briefly describes biochemical mechanism of IS development.

Influence of vitamin C on markers of oxidative stress in the earliest period of ischemic stroke.

Experimental studies have demonstrated that oxidative stress plays an essential role in the pathophysiology of ischemic stroke. The objective of the present study was to assess some serum markers of oxidative stress in patients in the early period of ischemic stroke and determine whether vitamin C supplementation affects the parameters of oxidative stress and the clinical status of patients. The study included 60 patients with ischemic stroke and 20 controls. Patients with ischemic stroke were divided into two groups: group I (n = 30), which did not receive vitamin C therapy, and group II (n = 30), which received vitamin C (500 mg/day, i.v.) for 10 days beginning on day 1 after ischemic stroke. Blood levels of bilirubin, creatinine, uric acid and total antioxidative capacity (TAC) were measured on stroke-days 1, 3, 5, and 10. Moreover, the neurological status of patients was evaluated on the same days using the NIHSS, Rankin and Bartel scales. Neurological status was also assessed with the Rankin scale after 3 months. Uric acid and TAC were decreased in group I on all measurement days. However, we did not observe any differences in the clinical status of patients receiving vitamin C during the first ten days of stroke or after 3 months. Although administration of vitamin C (500 mg/day, iv) to ischemic stroke patients since the first day ischemic stroke resulted in elevated serum levels of antioxidants, it did not substantially improve the clinical and functional status of patients after 3 months.

Enkephalin derivative, cyclo[Nepsilon,Nbeta-carbonyl-D-Lys2, Dap5] enkephalinamide (cUENK6), induces a highly potent antinociception in rats.

The aim of the study was to evaluate whether the newly synthesized analog of enkephalin, cyclo[N(epsilon),N(beta)-carbonyl-D-Lys(2), Dap(5)] enkephalinamide (cUENK6), a highly potent mu- (guinea pig ileum assay) and delta-receptors (mouse vas deferens assay) ligand, induces an antinociceptive effect in the hot-plate test and tail-immersion test after intracerebroventricular administration. Our study indicated that this peptide at the dose of 0.25 nmol produced comparable but at the dose of 0.5 nmol stronger than morphine (13 nmol), antinociceptive effect in both tests. Furthermore, rats with developed tolerance to morphine indicated cross-tolerance to antinociceptive effects of cUENK6. The antinociceptive effects of cUENK6 and morphine were inhibited by non-selective opioid receptor antagonist--naloxone. More detailed study indicated that the delta-opioid receptor antagonist - naltrindole very strongly and, to the lower extent, mu-opioid antagonist - beta-funaltrexamine (beta-FNA), inhibited antinociceptive effect of cUENK6 in the tail-immersion test. Nor-binaltorphimine (nor-BNI), a kappa-opioid receptor antagonist, did not influence this effect. These data suggest the dominant role of delta-opioid receptors as compared with mu-receptors in mediation antinociceptive effect of cUENK6. Furthermore, we found that cUENK6 is much more effective in inhibiting pain in the hot-plate (ED(50)=0.0792 nmol) than in the tail-immersion (ED(50)=0.3526 nmol) test. However, cUENK6 at the antinociceptive doses induced hypolocomotion, and although this effect is observed after administration of opioid agonists in rats as a one phase of their biphasic action (inhibition followed by activation), in our study it was not naloxone-reversible. Therefore, our study suggests that not only opioid receptors may be involved in behavioral effects of cUENK6.

[Oxidative stress in cerebral stroke]. / Stres oksydacyjny w udarze mózgu.

Free radicals are molecules or ions containing non-paired electrons on the external orbit, which ensures their high chemical activity. In systemic homeostasis, free radicals are inactivated by endo- and exogenous antioxidants and do not have destructive effects. The human organism possesses protective mechanisms, i.e. enzymatic systems (peroxide dismutase, glutathione peroxidase, catalase) and non-enzymatic systems (vitamin C and E selenium, coenzyme Q, lipoid acid, bilirubin). Imbalance between continuous production of reactive oxygen forms and their elimination due to enzymatic and non-enzymatic neutralization reactions as well as effects of exogenous antioxidants is defined as oxidative stress. Recent studies demonstrated a significant role of inflammatory processes and oxidative stress in the pathomechanism of cerebral stroke. Increased production of free radicals was observed in both the ischaemic and haemorrhagic strokes and oxidative stress was shown to be one of the causative mechanisms of tissue damage in these diseases. This was confirmed by numerous studies assessing the concentration of oxidative stress biomarkers and levels of plasma antioxidants (enzymatic and non-enzymatic). At present, studies are being carried out about the use of antioxidative substances for the therapy of cerebral stroke. The present study reports current findings concerning oxidative stress issues in patients with stroke.