ascorbic-acid and Subarachnoid-Hemorrhage

The antiproteasic activity of alpha1-antitrypsin (alpha1-AT) is reduced in cases of subarachnoid hemorrhage from ruptured intracranial aneurysm and particularly in patients currently smoking; alpha1-AT is very sensitive to oxidant agents. About 50% of physiological anti-oxidant systemic capacity is represented by Vitamin A, E and C. Plasmatic amounts of alpha1-AT, alpha1-AT Collagenase Inhibitory Capacity (CIC) and levels of vitamin A, vitamin E and vitamin C were analyzed in 39 patients, 26 women and 13 men, operated for intracranial aneurysm; 11 patients with unruptured intracranial aneurysm were considered as controls while 28 patients were included within 12 hours from subarachnoid hemorrhage (SAH). Plasmatic levels of vitamin A and vitamin E were significantly lower (p=0.038 and p=0.0158) in patients suffering SAH than in controls, while no statistically significant differences were found in mean plasmatic vitamin C levels. Level of alpha1-AT was not statistically different in controls and in patients with SAH; however, the activity of alpha1-AT, evaluated as CIC, is significantly reduced in patients with SAH (p=0.019). We have observed that systemic plasmatic levels of vitamins did not significantly differ in relation to smoking habit. Vitamin A and E represent an important defensive system against free radicals reactions. Particularly, vitamin E acts as an antioxidant by scavenging free-radicals. A reduced anti-oxidant status might be related to the higher sensibility of alpha1-AT to oxidative reactions and the activity of alpha1-AT is dependent on the antioxidant capacity of liposoluble vitamins. We can speculate that an acute systemic oxidative stress condition might influence the rupture of intracranial aneurysms.

Topics: alpha 1-Antitrypsin; Antioxidants; Ascorbic Acid; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Oxidative Stress; Smoking; Subarachnoid Hemorrhage; Vitamin A; Vitamin E

Increased vascular contractility plays a fundamental role in cerebral vasospasm in subarachnoid haemorrhage (SAH). We investigated the role of thrombin and its receptor, proteinase-activated receptor 1 (PAR1), and other G protein-coupled receptors in the increased contractility, and examined the preventive effects of the thrombin inhibitor, argatroban, and anti-oxidative agents, vitamin C and tempol.. A rabbit model of SAH was utilized. Contractile responses of the isolated basilar artery and the level of oxidative stress of brain tissues were evaluated.. Contractile responses to thrombin and PAR1-activating peptide (PAR1-AP) were enhanced and prolonged after SAH. The thrombin-induced contraction persisted even after terminating thrombin stimulation. When sequentially stimulated with PAR1-AP, the second response was maintained in SAH, while it was substantially attenuated in the control. Only a combination of argatroban with vitamin C or tempol prevented both the enhancement and prolongation of the contractile response to PAR1-AP and restored the reversibility of the thrombin-induced contraction. The responses to angiotensin II, vasopressin and PGF(2α) were enhanced and prolonged after SAH to varying degrees, and responded differently to the treatment. The response to vasopressin exhibited a similar phenomenon to that seen with PAR1-AP. Oxidative stress was increased in SAH, and normalized by the treatment with argatroban, vitamin C or their combination.. Increased vascular reactivity to agonists in SAH was attributable to the enhancement and prolongation of the contractile response. A combination of argatroban and anti-oxidative agents was required to prevent both the enhancement and prolongation of the contractile response.

Topics: Animals; Antioxidants; Arginine; Ascorbic Acid; Drug Therapy, Combination; Male; Pipecolic Acids; Rabbits; Receptor, PAR-1; Signal Transduction; Subarachnoid Hemorrhage; Sulfonamides; Thiobarbituric Acid Reactive Substances; Thrombin; Thrombosis; Vasoconstriction

Cerebral vasospasm (CVS) is a common serious complication after the spontaneous subarachnoid hemorrhage (SAH). Despite recent advances in medical and surgical treatments, the 30-day mortality rate of SAH remains high, and there is lack of especially effective clinical treatment to alleviate and improve CVS. The present study has investigated the therapeutic effect of insulin and vitamin C on CVS after SAH.. Five days after SAH, there is obvious basilar artery spasm in SAH group, whose average vascular cross-sectional area (233,099 ± 16,750 μm²) is significantly smaller than that in control group (462,128 ± 74,756 μm²), which is also significantly different from those in SAH + insulin group (221,114 ± 43,457 μm²) and SAH + vitamin C group (237,820 ± 21,703 μm²). SAH + insulin + vitamin C group shows no evident vasospasm and maintains a vascular cross-sectional area of 425,530 ± 45,503 μm², which is significantly different from that in SAH group. Insulin receptor α (InRα) expression is significantly downregulated in the vascular endothelial cells of SAH, SAH + insulin, and SAH + vitamin C groups (P < 0.01) but remains unchanged in vascular endothelial cells of SAH + insulin + vitamin C group (P > 0.05). Five days after SAH, serum and cerebrospinal fluid NO levels in SAH, SAH + insulin, and SAH + vitamin C groups decrease significantly (P < 0.01) compared to that in control group, whereas the reduction is not evident in SAH + insulin + vitamin C group (P > 0.05).. Combinatorial treatment with insulin and vitamin C has effectively relieved the CVS after SAH in rabbit, possibly through increasing the InRα expression and NO level, whereas treatment with insulin or vitamin C alone fails to do so.

Topics: Animals; Ascorbic Acid; Disease Models, Animal; Drug Therapy, Combination; Hypoglycemic Agents; Insulin; Rabbits; Subarachnoid Hemorrhage; Vasospasm, Intracranial; Vitamins

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Cerebral Ventricles; Drainage; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Oxyhemoglobins; Subarachnoid Hemorrhage; Therapeutic Irrigation; Time Factors; Vasospasm, Intracranial

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Cerebral Ventricles; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Plasminogen Activators; Subarachnoid Hemorrhage; Therapeutic Irrigation; Tomography, X-Ray Computed; Treatment Outcome; Urokinase-Type Plasminogen Activator; Vasospasm, Intracranial

Cisternal irrigation therapy with urokinase and ascorbic acid was introduced to prevent symptomatic vasospasm after aneurysmal subarachnoid hemorrhage (SAH). To dissolve and wash out the subarachnoid clot, cisternal irrigation with urokinase is used. Ascorbic acid is added to degenerate oxy-hemoglobin, one of the strongest spasmogenic substances, into verdohemelike products, which are nonspasmogenic. The efficacy and safety of this therapy were evaluated.. This therapy was performed consecutively in 217 patients. The degree of SAH of the patients was classified as Fisher CT Group 3, and the highest CT number (Hounsfield number) exceeded 60 in the SAH, which suggested a significant risk for symptomatic vasospasm. All patients underwent surgery within 72 hours from the onset of SAH. After clipping the aneurysm, irrigation tubes were placed in the Sylvian fissure (inlet) unilaterally or bilaterally and in the prepontine or chiasmal cistern (outlet). Lactated Ringer's solution with urokinase (120 IU/mL) and ascorbic acid (4 mg/mL) was infused at a rate of 30 mL/hour/side for approximately 10 days.. Of the 217 patients studied, symptomatic vasospasm was observed in 6 cases (2.8%), and two of these six cases (0.9%) demonstrated sequelae. The average total blood volume calculated from the drainage fluid was approximately 114 mL. Analysis of the absorption spectrum of the drainage fluid revealed disappearance of the oxy-hemoglobin-specific 576-nm peak. Complications occurred in eight patients during irrigation therapy; two patients experienced seizures, two patients developed meningitis, and four patients had an intracranial hemorrhage. However, all of these patients recovered without neurological deficits.. These results suggest that cisternal irrigation therapy with urokinase and ascorbic acid is effective in preventing symptomatic vasospasm after aneurysmal SAH.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Cisterna Magna; Clinical Protocols; Female; Free Radical Scavengers; Humans; Intracranial Aneurysm; Male; Middle Aged; Oxyhemoglobins; Plasminogen Activators; Radionuclide Imaging; Radiopharmaceuticals; Subarachnoid Hemorrhage; Technetium Tc 99m Pentetate; Therapeutic Irrigation; Tomography, X-Ray Computed; Treatment Outcome; Urokinase-Type Plasminogen Activator; Vasospasm, Intracranial

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

Topics: Antioxidants; Ascorbic Acid; Cisterna Magna; Humans; Intracranial Aneurysm; Plasminogen Activators; Subarachnoid Hemorrhage; Therapeutic Irrigation; Treatment Outcome; Urokinase-Type Plasminogen Activator; Vasospasm, Intracranial

The pathophysiology of subarachnoid hemorrhage (SAH) may involve free radical production and lipid peroxidation. We examined plasma levels of cholesteryl ester hydroperoxides (CEOOH) and antioxidants in 25 patients with SAH, and 10 neurologic controls with lacunar stroke. Patients with SAH had significantly increased plasma levels of CEOOH, which peaked on day 5 after the ictus. Concentrations of CEOOH were significantly increased, and ascorbic acid concentrations were significantly decreased in patients who developed vasospasm compared with patients without vasospasm. Increased levels of CEOOH were associated with increased mortality and correlated with clinical outcome scales. These results implicate oxidative stress in the pathogenesis of SAH and suggest that measurements of CEOOH in plasma may be useful both prognostically as well as in monitoring therapeutic interventions.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Biomarkers; Cholesterol Esters; Female; Humans; Lipid Peroxides; Male; Middle Aged; Oxidation-Reduction; Severity of Illness Index; Subarachnoid Hemorrhage; Ubiquinone; Uric Acid; Vitamin E

Using microdialysis, levels of metabolites in the extracellular fluid of the cerebral cortex were monitored during neurovascular surgery (9 aneurysm and 5 extra-intracranial bypass operations). Our aim was to use microdialysis to detect any local ischemia which might be caused by brain retraction or temporary clipping. Parameters were therefore quantified whose levels in the dialysate are known to be influenced by ischemia (on-line pH, ascorbic acid, uric acid, glutathione, cysteine, glucose, lactate, glucose:lactate ratio). In the aneurysm series, on-line pH fell after introduction of the retractor, and in the majority of cases the other parameters also showed changes in accordance with ischemic conditions in the region of the probe. These changes disappeared at the end of retraction, or sometimes even before. During the bypass operations, there were no marked changes in on-line pH or in any of the measured parameters. However, in some of these patients values for the glucose:lactate ratio, ascorbic acid and uric acid lay outside the suggested basal levels for minimally disturbed cortex, indicating possible changes in metabolism caused by inadequate perfusion (carotid artery occlusion). We conclude that microdialysis is a sensitive method of detecting intraoperative changes in cerebral metabolism.

Topics: Ascorbic Acid; Biomarkers; Brain Ischemia; Carotid Artery Diseases; Carotid Artery, Internal; Cerebral Cortex; Cerebral Revascularization; Constriction; Cysteine; Energy Metabolism; Extracellular Space; Glucose; Glutathione; Humans; Hydrogen-Ion Concentration; Intracranial Aneurysm; Intraoperative Complications; Lactates; Microdialysis; Monitoring, Intraoperative; Sensitivity and Specificity; Subarachnoid Hemorrhage; Uric Acid

We will report on our preliminary findings using microdialysis to monitor three patients in intensive care with either severe head injury (SHI) or severe subarachnoid hemorrhage (SAH) for up to 72 hours. In addition, basal levels in uninjured brain were assessed during an extra-intracranial bypass operation. Samples were collected hourly or half-hourly (flow rate 2 microliters/min, perfusion medium 0.9% saline). Parameters measured were the antioxidants ascorbic acid, uric acid, glutathione and cysteine. In 2 patients, the pH of the dialysate (pHD) was also measured on-line with a specially constructed flow-through meter, and glucose and lactate levels were assessed in the dialysate. In patient 1 (SHI), there was practically no cerebral perfusion pressure because of high ICP; cysteine and lactate levels were very high and glucose not measurable. In patient 2 (SAH) a hypoxic episode was accompanied by increased uric acid and decreased glucose. In patient 3 (SHI), the pHD reflected normalisation of blood gases after hyperventilation. Results indicate that parameters are in the range known from experimental studies, and can be correlated with clinical situations. The pHD as valuable indicator of metabolic changes is also feasible bedside.

Topics: Acid-Base Equilibrium; Adult; Ascorbic Acid; Blood Glucose; Blood-Brain Barrier; Brain Edema; Brain Injuries; Cerebrospinal Fluid Shunts; Craniotomy; Critical Care; Cysteine; Energy Metabolism; Female; Glutathione; Humans; Hydrogen-Ion Concentration; Hypoxia, Brain; Intracranial Pressure; Lactates; Lactic Acid; Male; Microdialysis; Middle Aged; Monitoring, Physiologic; Online Systems; Postoperative Complications; Signal Processing, Computer-Assisted; Subarachnoid Hemorrhage; Uric Acid

Topics: Aged; Animals; Ascorbic Acid; Cats; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Subarachnoid Hemorrhage

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Astrocytoma; Cerebral Hemorrhage; Congenital Abnormalities; Humans; Intracranial Aneurysm; Subarachnoid Hemorrhage