ascorbic-acid and Cerebral-Infarction

The paper reviews the preliminary results of a multicenter randomized clinical research. The aim of the study was to determine the optimal duration of different types of energy-correction therapy. 99 case report forms of patients with cerebral infarction were reviewed with their prior envelope randomization into three groups. Patients in the first group (experimental group), consisting of 32 patients, as part of combined therapy received ascorbic acid (5% solution twice a day in a recommended dosage of 20 ml/day for 20 days); the second group (37 patients) received 10 ml of cytoflavin intravenously by drop infusion twice a day for 10 days; the third group received cytoflavin for 20 days (from day 1 to day 10 - 20 ml a day, from day 11 to day 20 - 10 ml a day). The average NIH scale score on admission was 14.9 ± 2.6. Prescription of cytoflavin came with average 1.7 - 1.8 time regression (p < 0.05) of the volumes of cerebral ischemia in the of cases of the 10- and 20-day courses of treatment, while there were no significant morphologic changes in the ascorbic acid group. These results correlated with the best dynamics and outcomes of the neurological and performance status of patients receiving cytoflavin. Despite the lack of significant general differences in the clinical and morphological data of the second and third groups, the patients with underlying grave medical condition in the 20-day cytoflavin group (with NIH score of 14-20 points on admission) tended to have improved neurologic status parameters in comparison with the experimental group and the 10-day cytoflavin group. These results attest to the advantages of personalized antioxidant energy-correction therapy.

Topics: Aged; Antioxidants; Ascorbic Acid; Cerebral Infarction; Cognition; Drug Administration Schedule; Drug Combinations; Female; Flavin Mononucleotide; Humans; Inosine Diphosphate; Male; Middle Aged; Niacinamide; Precision Medicine; Psychological Tests; Russia; Severity of Illness Index; Succinates; Treatment Outcome

This study aims to evaluate the efficacy and safety of α-lipoic acid in the treatment of aged type 2 diabetes mellitus (T2DM) complicated with acute cerebral infarction.. 90 patients were randomly divided into two groups, on the basis of conventional treatment. The experiment group was administrated with α-lipoic acid, while only Vitamin C for the control group, for 3 consecutive weeks. Before and after the experiment, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) levels were measured and scored with the NIHSS (National Institutes of Health Stroke Scale), and the changes of blood glucose, insulin function and other indicators were observed.. After the treatment, the plasma SOD and GSH-Px levels increased, while MDA decreased (p < 0.05), with statistical significance when compared with the control group (p < 0.01). NIHSS score, blood glucose, blood lipids and HOMA-IA of the experiment group decreased significantly (p < 0.01); and no significant adverse reactions were found in both groups.. α-lipoic acid was safe and effective in the treatment of aged T2DM complicated with acute cerebral infarction, significantly reducing the patient's oxidative stress, blood glucose and lipid levels and being able to improve islet function.

Topics: Acute Disease; Aged; Aging; Antioxidants; Ascorbic Acid; Blood Glucose; Cerebral Infarction; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Oxidative Stress; Thioctic Acid; Treatment Outcome

To examine the role of increased oxidative stress in the pathogenesis of cerebral infarction in stroke in stroke-prone spontaneously hypertensive rats (SHR-SP).. The differentially expressed brain protein profile was examined in spontaneously hypertensive rats (SHR) (control group) and SHR-SP using two-dimensional fluorescent difference gel electrophoresis (2D-DIGE). In addition, oxidative stress indicators including total antioxidation capacity (TAC), glutathione peroxidase (GPx) activity, and maleic dialdehyde (MDA) were also measured. Lastly, SHR-SP were randomly divided into untreated and treated (vitamins C (200 mg/kg/day) and E (100 mg/kg/day)) groups. After treatment for 4 weeks, half of the animals were sacrificed for detection of TAC, GPx, and MDA. The remaining rats underwent middle cerebral artery occlusion (MCAO) and the infarct areas were measured.. Compared with SHR, the infarct area of SHR-SP was larger (P < 0.01), and the antioxidative proteins including glutathione S-transferase (GST) Pi2 and GST A5 were lower; TAC and GPx activities were decreased and MDA levels. Treatment with vitamins C and E decreased MDA, and increased TAC and GPx activity significantly in SHR-SP, while also decreasing the infarct area (P < 0.01).. Our findings indicate that oxidative stress plays an important role in the pathogenesis of cerebral ischemia.

Topics: Aldehydes; Amino Acid Sequence; Animals; Antioxidants; Ascorbic Acid; Blotting, Western; Cerebral Infarction; Electrophoresis, Gel, Two-Dimensional; Glutathione Peroxidase; Image Processing, Computer-Assisted; Infarction, Middle Cerebral Artery; Lipid Peroxidation; Male; Mass Spectrometry; Molecular Sequence Data; Nerve Tissue Proteins; Oxidative Stress; Rats; Rats, Inbred SHR; Stroke; Vitamin E; Vitamins

Experimental stroke studies indicate that oxidative stress is a major contributing factor to ischemic cerebral injury. Oxidative stress is also implicated in activation of matrix metalloproteinases (MMPs) and blood-brain barrier injury after ischemia-reperfusion. Plasma biomarkers of oxidative stress may have utility as early indicators of efficacy in Phase 2 trials of antioxidant therapies in human stroke. To date, a valid biomarker has been unavailable. We measured F2-isoprostanes (F2IPs), free-radical induced products of neuronal arachadonic acid peroxidation, in acute ischemic stroke. We aimed to determine the change in plasma F2IP levels over time and relationship with plasma MMP-9 in tPA-treated and tPA-untreated stroke patients.. We performed a case-control study of consecutive ischemic stroke patients (25 tPA-treated and 27 tPA-untreated) presenting within 8 hours of stroke onset. Controls were individuals without prior stroke from a primary care clinic network serving the source population from which cases were derived. Infarct volume was determined on acute diffusion-weighted MRI (DWI) performed within 48 hours using a semi-automated computerized segmentation algorithm. Phlebotomy was performed at <8 hours, 24 hours, 2 to 5 days, and 4 to 6 weeks. F2IPs were measured by gas chromatography/mass spectrometry and MMP-9 by ELISA. Prestroke antioxidant dietary intake was measured by the 24-hour recall method.. In 52 cases and 27 controls, early (median 6 hours postonset) F2IPs were elevated in stroke cases compared with controls (medians 0. 041 versus 0.0295 pg/mL, P=0.012). No difference in F2IPSs was present at later time points. Early plasma F2IPs correlated with MMP-9 in all patients (P=0.01) and the tPA-treated subgroup (P=0.02). No correlation was found with NIHSS, DWI infarct volume, 90-day Rankin score, or C-reactive protein (P>0.05 for all).. In early human stroke we found evidence of increased oxidative stress and a relationship with MMP-9 expression, supporting findings from experimental studies.

Topics: Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Biomarkers; Brain Ischemia; Case-Control Studies; Cerebral Infarction; Diffusion Magnetic Resonance Imaging; F2-Isoprostanes; Female; Fibrinolytic Agents; Humans; Male; Matrix Metalloproteinase 9; Middle Aged; Oxidative Stress; Severity of Illness Index; Stroke; Tissue Plasminogen Activator; Treatment Outcome

Oxidative damage has been implicated in the pathogenesis of cerebral ischemia. We previously demonstrated that exogenously supplied dehydroascorbic acid (DHA), an oxidized, blood-brain barrier transportable form of the antioxidant ascorbic acid (AA), improves outcome after experimental stroke.. To investigate the neuroprotective effect of DHA therapy, we measured cerebral AA levels using a novel assay, quantified markers of lipid peroxidation, and evaluated infarct volume after reperfused stroke in a murine model. All experiments were performed using a new citrate/sorbitol-stabilized DHA formulation to improve the stability of the compound.. Intraparenchymal AA levels declined after cerebral ischemia/reperfusion and were repleted in a dose-dependent fashion by postischemic administration of intravenous DHA (P < 0.01). Repletion of these levels was associated with reductions in cerebral malondialdehyde levels (P < 0.05), which were also elevated after reperfused stroke. DHA repletion of interstitial AA levels and reduction in cerebral lipid peroxidation was associated with dose-dependent reductions in infarct volume (P < 0.05).. Together, these results indicate that an intravenous cerebroprotective dose of citrate/sorbitol-stabilized DHA is correlated with increased brain ascorbate levels and a suppression of excessive oxidative metabolism.

Topics: Animals; Antioxidants; Ascorbic Acid; Brain Ischemia; Cerebral Cortex; Cerebral Infarction; Citric Acid; Dehydroascorbic Acid; Disease Models, Animal; Excipients; Infarction, Middle Cerebral Artery; Injections, Intravenous; Lipid Peroxidation; Mice; Mice, Inbred C57BL; Nerve Degeneration; Neuroprotective Agents; Oxidative Stress; Reperfusion Injury; Sorbitol; Treatment Outcome; Up-Regulation

To explore the association of risk for human cerebral hemorrhage with blood cholesterol, free radicals, oxidation and lipoperoxidation.. 351 cerebral hemorrhage patients (CHP) in the acute phase and 100 healthy adult volunteers (HAV) were investigated by testing the contents of cholesterol (CH), lipoperoxides (LPO), nitric oxide (NO), vitamin C (VC) and vitamin E (VE) and activities of superoxide dismutase (SOD) in plasma and erythrocytes (RBC), and by assessing the contents of CH and LPO in RBC with spectrophotometric assays.. Compared with the average values (AV) of the above biochemical parameters (BP) in the HAV group, the AV of CH in plasma and RBC, VC and VE in plasma as well as SOD in plasma and RBC in the CHP group were significantly decreased (P = 0.0000), while the AV of the LPO in plasma and RBC as well as NO in plasma in the CHP group were significantly increased (P = 0.0000). The findings of linear correlation analysis for the CHP group showed that the above biochemical parameters were significantly correlated with both intracranial hemorrhagic sizes (IHS) and neurotic functional defective scales (NDS). The findings of stepwise correlation analysis for the CHA group suggested that HIS was closely correlated with the values of CH and LPO in RBC as well as NO and VE in plasma, and that NDS was closely correlated with the values of CH and LPO in RBC as well as NO and VC in plasma.. The findings of the present study suggest that marked low RBC cholesterol and marked high RBC lipoperoxides may constitute the potential main risk factors for human cerebral hemorrhage, and that the oxidative and lipoperoxidative stress in the CHP bodies is pathologically aggravated, leading to the oxidative and lipoperoxidative damages in the CHP.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Cerebral Hemorrhage; Cerebral Infarction; Cholesterol; Erythrocytes; Female; Free Radicals; Humans; Lipid Peroxidation; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Risk Factors; Superoxide Dismutase; Vitamin E

Free radical generation and consequent oxidative stress in thrombotic cerebrovascular stroke have a distinctive role in the pathogenesis of ischemic brain injury. One of the potential injurious effects of homocyst(e)ine in occlusive vascular diseases is free radical generation. In the current study, we investigated the status of oxidant stress in the acute phase of thrombotic cerebrovascular stroke and the possible role of homocyst(e)ine.. We determined levels of plasma homocyst(e)ine, lipid peroxide, ascorbic acid, superoxide dismutase, and nitric oxide in 30 patients with thrombotic cerebrovascular stroke within 2 days of the onset of the attack as well as in 22 healthy volunteers of comparable age and gender.. Statistically significant elevation of homocyst(e)ine (P<0. 001), lipid peroxide (P<0.001), and nitric oxide (P<0.001) plasma levels were observed in stroke patients compared with healthy controls. On the other hand, the antioxidant ascorbic acid plasma levels were significantly lower in the patient group compared with healthy control subjects (P<0.001). Meanwhile, superoxide dismutase plasma levels were not statistically different in either groups. The study also revealed a significant and strong positive correlation between homocyst(e)ine and lipid peroxide (r=0.85, P<0.001). Ascorbic acid plasma levels were significantly negatively correlated with both homocyst(e)ine (r=-0.875, P<0.001) and lipid peroxide (r=-0.576, P<0.001). The nitric oxide level was positively correlated with superoxide dismutase (r=0.396, P<0.05).. We conclude that hyperhomocyst(e)inemia is a possible causal factor in free radical generation during the acute phase of thrombotic cerebrovascular stroke. Pharmacological intervention could potentially be beneficial in this setting and warrants further evaluation.

Topics: Acute Disease; Ascorbic Acid; Biomarkers; Cerebral Infarction; Female; Free Radical Scavengers; Homocysteine; Humans; Intracranial Thrombosis; Lipid Peroxides; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Prognosis; Risk Factors; Superoxide Dismutase

Epidemiological evidence suggests that vitamin C may decrease the risk of stroke. The purpose of the present study was to examine the association of serum vitamin C concentration with the subsequent incidence of stroke.. In a Japanese rural community, a cohort of 880 men and 1241 women aged 40 years and older who were initially free of stroke was examined in 1977 and followed until 1997. The baseline examination included a measurement of serum vitamin C concentration. The incidence of stroke was determined by annual follow-up examinations and registry.. During the 20-year observation period, 196 incident cases of all stroke, including 109 cerebral infarctions and 54 hemorrhagic strokes, were documented. Strong inverse associations were observed between serum vitamin C concentration and all stroke (sex- and age-adjusted hazard ratios were 0.93, 0.72, and 0.59, respectively, for the second, third, and fourth quartiles compared with the first quartile; P for trend=0.002), cerebral infarction (0.71, 0.59, and 0.51; P for trend=0.015), and hemorrhagic stroke (0.89, 0.75, and 0. 45; P for trend=0.013). Additional adjustments for blood pressure, serum total cholesterol, body mass index, physical activity, smoking, alcohol drinking, antihypertensive medication, atrial fibrillation, and history of ischemic heart disease did not attenuate these associations markedly.. Serum vitamin C concentration was inversely related to the subsequent incidence of stroke. This relationship was significant for both cerebral infarction and hemorrhagic stroke. Additional mechanistic hypotheses may be required to explain our findings.

Topics: Adult; Age Distribution; Aged; Ascorbic Acid; Cerebral Hemorrhage; Cerebral Infarction; Cohort Studies; Comorbidity; Diet; Female; Follow-Up Studies; Humans; Incidence; Japan; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Risk Factors; Rural Population; Sex Distribution; Stroke

Antioxidants may protect against atherosclerosis and thus prevent cerebrovascular disease. We studied the association between dietary antioxidants and subtypes of stroke.. The study cohort consisted of 26 593 male smokers, aged 50 to 69 years, without a history of stroke. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire at baseline. Incident cases were identified through national registers.. During a 6.1-year follow-up, 736 cerebral infarctions, 83 subarachnoid hemorrhages, and 95 intracerebral hemorrhages occurred. Neither dietary flavonols and flavones nor vitamin E were associated with risk for stroke. The dietary intake of beta-carotene was inversely associated with the risk for cerebral infarction (relative risk [RR] of highest versus lowest quartile 0.74, 95% CI 0.60 to 0. 91), lutein plus zeaxanthin with risk for subarachnoid hemorrhage (RR 0.47, 95% CI 0.24 to 0.93), and lycopene with risks of cerebral infarction (RR 0.74, 95% CI 0.59 to 0.92) and intracerebral hemorrhage (RR 0.45, 95% CI 0.24 to 0.86). Vitamin C intake was inversely associated with the risk for intracerebral hemorrhage (RR 0.39, 95% CI 0.21 to 0.74). After simultaneous modeling of the antioxidants, a significant association remained only between beta-carotene intake and risk for cerebral infarction (RR 0.77, 95% CI 0.61 to 0.99).. Dietary intake of beta-carotene was inversely associated with the risk for cerebral infarction. No association was detected between other dietary antioxidants and risk for stroke.

Topics: Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cerebral Hemorrhage; Cerebral Infarction; Cohort Studies; Comorbidity; Diet; Finland; Flavonoids; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Risk; Risk Assessment; Smoking; Stroke; Subarachnoid Hemorrhage; Vitamin E; Vitamins

Temporary occlusion of major cerebral blood vessels occasionally becomes necessary during surgical procedures. Ascorbic acid (Vitamin C) is an important non-enzymatic scavenger of free radicals and its protective effect on the brain in permanent focal cerebral ischaemia has been proven in a primate model of focal cerebral ischaemia [16]. Additional damage caused by reperfusion of the infarcted area has been shown in the rat model [22]. This study was undertaken to study the efficacy of ascorbic acid in decreasing infarct size in ischaemic reperfused brain. Maccaca radiata monkeys in the treated group were given two grams of ascorbic acid, parentally immediately before clipping the middle cerebral artery and the control group was given placebo. Reperfusion was done after four hours. Mean infarct size in all the three brain slices in the ascorbic acid pretreated group was 7.3% +/- 2.7 and in the placebo group 22.1 +/- 6.7 under similar conditions. The mean infarct size in the ascorbic acid pretreated group of monkeys was significantly lower when compared with the placebo group (p = 0.0003).

Topics: Animals; Ascorbic Acid; Brain; Brain Ischemia; Cerebral Infarction; Macaca radiata; Male; Neuroprotective Agents; Premedication; Rats; Reperfusion Injury

Neuronal cell damage following ischaemia is postulated to be due to free radical induced lipid peroxidation, and ascorbic acid is supposedly an important non-enzymatic scavenger of such free radicals. This study was undertaken to evaluate the protective effect of ascorbic acid on the brain in a primate model after focal cerebral ischemia. Consumption of ascorbic acid in the monkey brain following ischaemia and its effect on macroscopic infarct size as demonstrated by 2, 3, 5, Triphenyl tetrazolium chloride (TTC) staining were used as parameters. The monkeys in the treated group were given 1 gram ascorbic acid parenterally every day for six days. The mean level of total ascorbic acid in right basal ganglia was 35.1 +/- 4.2 micrograms/mg of protein in the treated group as opposed to 22.9 +/- 2.1 micrograms/mg of protein in the nontreated group both before ischaemia. After right middle cerebral artery occlusion to produce focal cerebral ischaemia, the total ascorbic acid in the right basal ganglia 2 hours post ischaemia was 13.3 +/- 3.1 micrograms/mg of protein in the treated group as opposed to 9 +/- 1.6 micrograms/mg of protein in the untreated group. The average consumption of total ascorbic acid was 21.8 micrograms/mg of protein in the treated group and 13.9 micrograms/mg of protein in the nontreated group. Macroscopic infarct size as determined by TTC staining in the right cerebral hemisphere was 11.7 +/- 6.9 in treated group whereas it was 24.4 +/- 4.4 (expressed as percentage of right hemisphere) in the non-treated group. There was significant reduction in the size of the infarct in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Ascorbic Acid; Basal Ganglia; Brain Ischemia; Cerebral Infarction; Female; Free Radicals; Lipid Peroxidation; Macaca radiata; Male; Mammillary Bodies; Optic Chiasm; Reactive Oxygen Species; Temporal Lobe

Oxygen free radicals have been implicated in the pathogenesis of brain injury induced by ischemia/reperfusion. We studied the role of endogenous reduced glutathione (GSH) in brain infarction associated with focal cerebral ischemia caused by permanent ligation of the right middle cerebral artery (MCA) and the right common carotid artery (CCA) plus temporary occlusion of the left CCA. GSH levels in the ischemic side of cortex decreased with time after ischemia and preceded cortical infarction estimated by the staining of mitochondrial respiratory enzymes with 2,3,5-triphenyltetrazolium chloride. GSH levels in the contralateral cortex were unchanged through the experimental periods. The extent of decrease of GSH levels and the severity of infarction in the ischemic cortex at 24 h after ischemia depended on the duration of occlusion of the left CCA. Depletion of brain GSH with buthionine sulfoximine, a selective inhibitor for gamma-glutamylcysteine synthetase, exacerbated cortical infarction and edema after ischemia. These results suggest that the endogenous brain GSH is an important determinant in the defense mechanisms against lesion formation after ischemia and support the possible role of oxygen radicals in the pathogenesis of ischemic brain injury.

Topics: Animals; Ascorbic Acid; Brain; Brain Ischemia; Buthionine Sulfoximine; Cerebral Infarction; Glutathione; Injections, Intraventricular; Male; Methionine Sulfoximine; Rats; Rats, Inbred Strains

Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia.

Topics: Animals; Ascorbic Acid; Body Water; Brain; Brain Chemistry; Cerebral Cortex; Cerebral Infarction; Glutathione; Humans; Ischemic Attack, Transient; Male; Mice; Mice, Transgenic; Superoxide Dismutase

The uptake of 99mTc-pertechnetate (TcO4), 99mTc-iron-ascorbic acid (Feasc), 99mTc-Solcocitran (Solcocitran), 99mTc-diphosphonate (HEDP) and 67Ga-citrate (Ga) in various brain lesions was compared. Influence of time from injection was also studied on the first three compounds. A rank correlation method was used to compare the scans which were judged visually by three independent observers. There was good agreement between the observers, as measured by Kendall's tau, but the concordance between rankings within the same type of lesion, as measured by Kendall's W, was rather poor. There was no significant difference in the uptake of TcO4, Feasc and Solcocitran. Ga showed generally poor uptake and its uptake in tumours and infarcts did not differ significantly. However, when HEDP and TcO4 were compared in two groups (I: Infarcts, haemorrhages and bone invading meningiomas, and II: Tumours not invaded into bone) a highly significant difference was obtained with much higher uptake of HEDP in Group I.

Topics: Adult; Ascorbic Acid; Brain Diseases; Brain Neoplasms; Cerebral Hemorrhage; Cerebral Infarction; Citrates; Diphosphonates; Gallium Radioisotopes; Humans; Organotechnetium Compounds; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium; Technetium Compounds