ascorbic-acid and Brain-Edema

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Brain Edema; Brain Injuries; Cohort Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glasgow Outcome Scale; Humans; Male; Middle Aged; Treatment Outcome; Vitamin E; Young Adult

Delayed treatment of stroke with recombinant tissue plasminogen activator (r-tPA) induces overexpression of matrix metalloproteinase 9 (MMP-9) which leads to breakdown of the blood-brain barrier (BBB) and causes more injuries to the brain parenchyma. In this study, the effect of ascorbic acid (AA), an antioxidant agent, on the delayed administration of r-tPA in a rat model of permanent middle cerebral artery occlusion (MCAO) was investigated. Forty male rats were randomly divided into four groups: untreated control rats (ischaemic animals), AA-treated (500 mg/kg; 5 hr after stroke) rats, r-tPA-treated (5 hr after stroke 1 mg/kg) rats and rats treated with the combination of AA and r-tPA. Middle cerebral artery occlusion was induced by occluding the right middle cerebral artery (MCA). Infarct size, BBB, brain oedema and the levels of MMP-9 were measured at the end of study. Neurological deficits were evaluated at 24 and 48 hr after stroke. Compared to the control or r-tPA-treated animals, AA alone (p < 0.001) or in combination with r-tPA (p < 0.05) significantly decreased infarct volume. Ascorbic acid alone or r-tPA + AA significantly reduced BBB permeability (p < 0.05), levels of MMP-9 (p < 0.05 versus control; p < 0.01 versus r-tPA) and brain oedema (p < 0.001) when compared to either the control or the r-tPA-treated animals. Latency to the removal of sticky labels from the forepaw was also significantly decreased after the administration of AA + r-tPA (p < 0.05) at 24 or 48 hr after stroke. Based on our data, acute treatment with AA may be considered as a useful candidate to reduce the side effects of delayed application of r-tPA in stroke therapy.

Topics: Animals; Antioxidants; Ascorbic Acid; Behavior, Animal; Blood-Brain Barrier; Brain; Brain Edema; Capillary Permeability; Disease Models, Animal; Drug Administration Schedule; Fibrinolytic Agents; Infarction, Middle Cerebral Artery; Male; Matrix Metalloproteinase 9; Motor Activity; Rats; Recombinant Proteins; Thrombolytic Therapy; Time Factors; Time-to-Treatment; Tissue Plasminogen Activator

Ascorbate is an essential antioxidant in the CNS, localized predominantly in neuronal cytosol. Slices of mammalian brain rapidly lose ascorbate, however, when incubated in ascorbate-free media; brain slices also take up water and swell. Here we investigated water gain in coronal slices of rat forebrain incubated with and without ascorbate for 1-3 h at 34 degrees C. Slices progressively gained water in ascorbate-free media, with a significant 12% water increase after 3 h at 34 degrees C, compared with the water content of slices after a 1-h recovery period at 24 degrees C, immediately following slice preparation. Inclusion of 400 micro M ascorbate in the medium led to an increase in tissue ascorbate content and prevented water gain at 34 degrees C. By contrast, water gain was not inhibited by isoascorbate or thiourea, which are antioxidants that are not accumulated in brain cells. The oxidant H2O2 enhanced water gain, whereas a cocktail of NMDA and non-NMDA receptor blockers inhibited edema formation to the same extent as ascorbate. These data demonstrate that brain edema, linked to glutamate-receptor activation, can result from intracellular oxidative stress and that this can be prevented by ascorbate.

Topics: Animals; Ascorbic Acid; Body Water; Brain Edema; In Vitro Techniques; Oxidative Stress; Prosencephalon; Rats; Receptors, Glutamate

Diabetes mellitus is a metabolic disorder associated with central nervous system impairments. Recent studies implicate oxidative stress mediated by reactive oxygen species (ROS) in the pathogenesis of diabetic complications. ROS have been shown to play role in the pathophysiology of brain injury. In the present study, closed head injury (CHI) was induced in diabetic rats to test the hypothesis that chronic oxidative stress exacerbates brain damage following CHI. Neurological recovery, edema, levels of low molecular weight antioxidants (LMWA), and markers of lipid peroxidation were determined at different intervals after injury. Diabetic rats (4 weeks after induction with streptozotocin) were subjected to CHI. Brain edema (percent water) and clinical status (neurological severity score) were assessed during 7 days. Brain LMWA were determined using cyclic voltammetry (CV) and HPLC-EC. In addition, conjugated dienes and thiobarbituric acid reactive substances (TBARS) were measured. Diabetic-CHI rats exhibited a lower rate of recovery and greater and more sustained edema (p < 0.01), as compared with the controls. At all times diabetic rats had higher levels of TBARS and conjugated dienes and lower concentrations of LMWA, and of vitamins C and E, suggesting chronic oxidative stress. At 5 min of CHI, the amounts of LMWA in control-CHI brains decreased (approximately 50%, p < 0.01) and returned to normal by 48 h and 7 days. In the diabetic-CHI brain only one class of LMWA slightly declined but remained low for 7 days. The present results support the hypothesis that diabetic rats are under chronic oxidative stress, and suffer greater neurological dysfunction, associated with further lipid peroxidation following CHI.

Topics: Animals; Ascorbic Acid; Brain; Brain Edema; Craniocerebral Trauma; Diabetes Mellitus, Experimental; Electric Conductivity; Electrophysiology; Male; Oxidative Stress; Rats; Rats, Wistar; Recovery of Function; Severity of Illness Index; Thiobarbituric Acid Reactive Substances; Vitamin E; Wounds, Nonpenetrating

Ascorbate and glutathione (GSH) are normally concentrated in brain cells at millimolar levels. However, both of these low-molecular-weight antioxidants are washed out of mammalian brain tissue during slice preparation and subsequent incubation. Ascorbate, which is not synthesized in the brain, can be added back to slices by active uptake from the incubation medium. Levels of GSH, on the other hand, are regulated by synthesis rather than uptake, and cannot be readily maintained in slices. Importantly, maintenance of brain slice ascorbate content at at least 50% of that in vivo, prevents the increase in slice water content that normally occurs during incubation. Slices with maintained ascorbate levels also have better histological characteristics than ascorbate-depleted tissue. The medium concentration of ascorbate sufficient to maintain content and inhibit edema formation is 400 microM, which is the normal concentration in brain extracellular fluid. This paper describes methods to maintain ascorbate levels in brain slices, including procedures to minimize oxidation in oxygenated incubation media. Also described is an HPLC analysis for ascorbate and GSH that is based on direct injection rather than extraction of samples.

Topics: Analysis of Variance; Animals; Ascorbic Acid; Brain; Brain Edema; Chromatography, High Pressure Liquid; Female; Glutathione; In Vitro Techniques; Pyramidal Cells; Rats; Rats, Sprague-Dawley

Ascorbate (reduced vitamin C) is an important enzyme cofactor, neuromodulator, and antioxidant that is stored at millimolar concentrations in the cytosol of cerebral astrocytes. Because these cells swell during hyponatremia, cerebral ischemia, and trauma, we investigated the effects of osmotic stress on astrocytic transport of ascorbate. Ascorbate efflux from primary cultures of rat astrocytes was rapidly (within 1 min) increased by incubation in hypotonic medium. Efflux also increased when astrocytes, which had been adapted to a hypertonic environment, were swollen by transfer to isotonic medium. Swelling-induced ascorbates efflux was inhibited by the anion-transport inhibitors 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS). The pathway that mediates ascorbate efflux was found to be selective because a larger anion, 2',7'-bis(carboxyethyl)-5-(or -6)-carboxyfluorescein (BCECF), was retained in the swollen astrocytes. Na(+)-dependent ascorbate uptake into astrocytes was inhibited slightly during the first minute of hypotonic stress, indicating that the sodium ascorbate cotransporter does not mediate swelling-induced efflux. Cell concentration of authentic ascorbate was measured by HPLC with electrochemical detection. When astrocytes were incubated in ascorbate-free medium, hypotonicity decreased cell ascorbate concentration by 50% within 3 min. When astrocytes were incubated in ascorbate-supplemented hypotonic medium, intracellular ascorbate concentration was restored within 10 min because uptake remained effective. Many pathological conditions cause brain cell swelling and formation of reactive oxygen species. Ascorbate release during during astrocytic swelling may contribute to cellular osmoregulation in the short-term and the scavenging of reactive oxygen species.

Topics: Adaptation, Physiological; Animals; Ascorbic Acid; Astrocytes; Biological Transport; Brain; Brain Edema; Culture Media; Hypertonic Solutions; Isotonic Solutions; Osmosis; Rats; Rats, Wistar

The aim of the present study was to investigate the oxidative status in astrocytoma. Samples of brain tissue from the centre to the periphery of the tumor were obtained from 11 astrocytoma patients undergoing computer tomography-guided stereotaxic operation, who had been previously treated with the corticosteroid dexamethasone. Part of the sample was investigated histologically for clarification of tumor type, and the presence of neoplastic and non-neoplastic tissue and necrosis. The rest was used for the quantification of the antioxidants ascorbic acid, uric acid, glutathione and cysteine by high performance liquid chromatography, and for quantification of DNA. Levels of antioxidants were calculated as micrograms/g fresh tissue and mumol/g DNA, a parameter related to cell content. There was significantly more DNA in neoplastic samples than in non-neoplastic ones, indicating increased cell density. Uric acid (micrograms/g fresh tissue) was significantly increased in neoplastic compared with non-neoplastic tissue, and levels were even higher in necrotic tissue. There were no significant differences between neoplastic and non-neoplastic tissue levels of ascorbic acid, glutathione or cysteine, expressed as micrograms/g fresh tissue. However, when levels of these three compounds were expressed as mumol/g DNA, i.e. taking into account the higher cell density, ascorbic acid, glutathione and cysteine were significantly reduced in neoplastic samples compared with non-neoplastic ones. Results thus show that there are differences between the antioxidant levels in astrocytoma and non-neoplastic tissue, providing additional support for the hypothesis that free radicals play a role in tumor growth.

Topics: Adult; Aged; Antioxidants; Artifacts; Ascorbic Acid; Astrocytoma; Biopsy; Brain Chemistry; Brain Edema; Brain Neoplasms; Combined Modality Therapy; Cysteine; Dexamethasone; DNA, Neoplasm; Female; Free Radicals; Glioblastoma; Glutathione; Humans; Male; Middle Aged; Necrosis; Neoplasm Proteins; Oxidation-Reduction; Oxidative Stress; Phenytoin; Solubility; Stereotaxic Techniques; Tomography, X-Ray Computed; Uric Acid; Water

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

Effect of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1, CAS 127061-56-7), a diester of alpha-tocopherol and ascorbic acid, on transient cerebral ischemia was studied in Mongolian gerbils. Cerebral energy metabolism and intracellular pH (pHi) were estimated employing in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Intraperitoneal injection of EPC-K1 (5 or 10 mg/kg) prior to ischemia significantly ameliorated pHi reduction in a dose dependent manner during ischemia. After reperfusion, energy and pHi recoveries were significantly faster in the EPC-K1 groups than in the control group. EPC-K1 (10 mg/kg) significantly reduced the extent of cerebral edema. Moreover, administration of EPC-K1 immediately after reperfusion significantly shortened the consciousness recovery in a dose dependent manner. The results suggest that EPC-K1 may exert protective effects on ischemic brain and may have therapeutic value in ischemic stroke.

Topics: Animals; Ascorbic Acid; Brain Chemistry; Brain Edema; Brain Ischemia; Consciousness; Dose-Response Relationship, Drug; Energy Metabolism; Gerbillinae; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Vitamin E

The authors present their results regarding the use of a buffered solution of glycerol 30%-sodium ascorbate 20% (GLIAS) for the treatment of brain oedema and intracranial hypertension. GLIAS was perfused intravenously in 80 patients with several types of brain oedema. In every patients serum and urinary osmolarity, diuresis, main blood and urine parameters, and ICP were monitored. Following GLIAS infusion an increase in plasma osmolarity was observed, changing the average basal value plus 13.4% after 15 min., 10.5% after 30'. At the same time there was a reduction of ICP and improvement in cerebral compliance. In each case there was a decrease in intracranial hypertension and brain oedema without significant collateral effects.

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Brain Edema; Brain Injuries; Brain Neoplasms; Buffers; Cerebral Hemorrhage; Child; Dose-Response Relationship, Drug; Female; Glycerol; Humans; Hypertonic Solutions; Infusions, Intravenous; Intracranial Aneurysm; Intracranial Pressure; Male; Middle Aged; Postoperative Complications; Pseudotumor Cerebri

Previous work has shown that unsaturated fatty acid components of model membrane phospholipids in vitro, damaged via a free radical mechanism, are protected by the presence of cholesterol in these membranes. The participation of these membrane lipids in the pathogenesis of traumatic injury to brain was studied in vivo using the Klatzo method of cryogenic injury in rats. Increased edema 4 hr after cryogenic injury was noted on the lesioned side. Total cerebral cholesterol was decreased significantly in the lesioned hemispheres 10 hr following injury. In lesioned animals pretreated and post-treated with methylprednisolone, there were no significant differences in the cholesterol levels. Arachidonic acid isolated from total membrane phospholipids was significantly reduced on the injured side 24 hr after injury, but not before. Other fatty acids were not significantly affected. Methylprednisolone treatment prevented the decrease in arachidonic acid. Animals that had received a cold injury had significant decreases in ascorbic acid levels after 4 hr on the lesioned side of the brain. This decrease was significantly ameliorated by corticosteroid administration. These results support the hypothesis that the protective effect of corticosteroids in cryogenic cerebral trauma may be due to antioxidant protection of major cell membrane lipid components such as cholesterol and phospholipids.

Topics: Animals; Ascorbic Acid; Brain; Brain Edema; Brain Injuries; Cholesterol; Fatty Acids, Unsaturated; Free Radicals; Freezing; Membrane Lipids; Methylprednisolone; Phospholipids; Rats; Rats, Inbred Strains

Topics: Animals; Ascorbic Acid; Brain Edema; Drug Therapy, Combination; Glucose; Glycerol; Humans; Intraocular Pressure; Rabbits

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Brain Edema; Child; Child, Preschool; Drug Therapy, Combination; Female; Glycerol; Humans; Injections, Intravenous; Male; Middle Aged; Pseudotumor Cerebri

Topics: Animals; Ascorbic Acid; Blood Pressure; Brain Diseases; Brain Edema; Dehydration; Glycerol; Hematuria; Injections, Intravenous; Intracranial Pressure; Male; Rabbits

Topics: Aesculus; Ascorbic Acid; Brain Edema; Capillary Permeability; Drug Therapy; Fagaceae; Flavones; Flavonoids; Hemorrhagic Disorders; Humans; Hypertension; Intracranial Arteriosclerosis; Rutin