ascorbic-acid and Spinal-Cord-Injuries

Many animal studies have evaluated the role of vitamins in the recovery of motor function after spinal cord injury, but their results have been contradictory and no consensus has been reached.. This meta-analysis aimed to investigate the effects of vitamin C and vitamin E on recovery of motor function after spinal cord injury in animal models.. Two authors independently collected the records of relevant articles published in MEDLINE, Embase, Scopus, and Web of Science through November 2018.. All studies conducted in animal models to evaluate the therapeutic effects of vitamin C or vitamin E or both on recovery of motor function after spinal cord injury were included. Studies that lacked a control group or a standard treatment, lacked an assessment of motor function, included genetically modified/engineered animals, included animals pretreated with vitamin C or vitamin E, or combined vitamin treatment with other methods, such as cell therapies, were excluded.. Data from 10 articles met the inclusion criteria for meta-analysis, conducted in accordance with PRISMA guidelines.. Daily supplementation with vitamin C (P < 0.0001) and vitamin E (P < 0.0001) significantly improved the recovery of motor function in animals affected by spinal cord injury. Vitamin C supplementation is effective only when administered intraperitoneally (P < 0.0001). Concurrent supplementation with both vitamins does not show better efficacy than treatment with either one alone.. Administration of vitamin C and vitamin E in animal models of spinal cord injury significantly improves the recovery of motor function.

Topics: Animals; Ascorbic Acid; Dietary Supplements; Humans; Recovery of Function; Spinal Cord Injuries; Vitamin E; Vitamins

Urinary tract infections (UTI) remain one of the most prevalent and frustrating morbidities for neurogenic bladder patients, and death attributed to urosepsis in the spinal cord injury (SCI) patient is higher when compared to the general population. Risk factors include urinary stasis, high bladder pressures, bladder stones, and catheter use. While classic symptoms of UTI include dysuria, increased frequency and urgency, neurogenic bladder patients present differently with increased spasticity, autonomic dysreflexia, urinary incontinence, and vague pains. Multiple modalities have been assessed for prevention including catheter type, oral supplements, bladder irrigation, detrusor injections and prophylactic antimicrobials. Of these, bladder inoculation with E. coli HU2117, irrigation with iAluRil(®), detrusor injections, and weekly prophylaxis with alternating antibiotics appear to have a positive reduction in UTI but require further study. Ultimately, treatment for symptomatic UTI should account for the varied flora and possible antibiotic resistances including relying on urine cultures to guide antibiotic therapy.

Topics: Administration, Intravesical; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Antibiotic Prophylaxis; Antioxidants; Ascorbic Acid; Botulinum Toxins, Type A; Catheter-Related Infections; Escherichia coli; Escherichia coli Infections; Humans; Immunotherapy, Active; Mannose; Methenamine; Multiple Sclerosis; Neuromuscular Agents; Proanthocyanidins; Probiotics; Recurrence; Spinal Cord Injuries; Urinary Bladder, Neurogenic; Urinary Catheterization; Urinary Catheters; Urinary Tract Infections

Oxygen radical-mediated lipid peroxidation appears to be a critical factor in posttraumatic neuronal degeneration. Thus, numerous studies have evaluated the neuroprotective efficacy of pharmacologic agents with lipid antioxidant activity in models of spinal cord and brain injury. Intensive pretreatment of animals with the endogenous lipid peroxyl radical scavenger alpha tocopherol (i.e., vitamin E) has been shown to decrease posttraumatic spinal cord ischemia and to enhance chronic neurologic recovery. However, the slow CNS tissue uptake of vitamin E requires chronic dosing, making it an impractical agent for the treatment of acute neural injury. The glucocorticoid steroid methylprednisolone has been shown to possess significant antioxidant efficacy and, when administered to animals or humans in antioxidant dosages, improves chronic neurologic recovery after spinal cord injury. This activity of methylprednisolone is independent of the steroid's glucocorticoid receptor-mediated actions. Novel antioxidant 21-aminosteroids have been developed that are devoid of glucocorticoid activity but have greater antioxidant efficacy than methylprednisolone. One of these, U74006F or tirilazed mesylate, has been shown to be effective in animal models of brain and spinal cord injury and is currently undergoing phase II clinical trials. Compounds that combine the amino functionality of the 21-aminosteroids with the peroxyl radical scavenging chromanol portion of vitamin E (i.e., 2-methylaminochromans) have also recently shown promise as neuroprotective agents. The consistent benefit afforded by antioxidant compounds adds further support to the concept that lipid peroxidation is an important therapeutic target for acute pharmacologic neuroprotection.

Topics: Animals; Antioxidants; Ascorbic Acid; Brain Injuries; Methylprednisolone; Spinal Cord Injuries; Steroids; Vitamin E

The effect of ascorbic acid on urine pH was studied in spinal cord injury patients. Their urine was not colonized by urease positive microorganisms. The study was designed to compare the baseline urine pH value and the urine pH value after the administration of placebo or ascorbic acid 500 mg/6 h. The diet and medical treatment were not controlled. A significant decrease in urine pH value was not obtained. There was no clinical benefit from the use of ascorbic acid.

Topics: Adolescent; Adult; Ascorbic Acid; Diet; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Single-Blind Method; Spinal Cord Injuries; Urease; Urinary Bladder, Neurogenic; Urinary Tract Infections

We conducted 202 trials in 161 male hospital patients to determine if prophylactic administration of ascorbic acid or antibacterials (trimethoprim-sulfamethoxazole, nalidixic acid, methenamine hippurate or nitrofurantoin macrocrystals) would prevent bacteriuria infections in spinal cord injury patients who had had at least 1 bout of bacteriuria. None of the drugs tested appeared to be statistically effective in the doses used in preventing bacteriuria in these patients. Moreover, sensitivities were lost to several drugs other than those used prophylactically. We conclude that use of prophylactic doses of ascorbic acid or antibacterials has not proved to be beneficial in spinal cord injury patients free of indwelling catheters.

Topics: Anti-Infective Agents, Urinary; Ascorbic Acid; Bacteriuria; Clinical Trials as Topic; Drug Combinations; Humans; Male; Methenamine; Nalidixic Acid; Nitrofurantoin; Spinal Cord Injuries; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Catheterization

The ability of ascorbic acid to lower urinary pH in patients with spinal cord injury and neurogenic bladder was studied. Ascorbic acid (1 g four times daily) or placebo was administered for five days in a double-blind, crossover study to 20 patients with spinal cord injury and neurogenic bladder. Urine pH was measured for two days before and during administration of placebo or ascorbic acid. The mean decrease in urinary pH with ascorbic acid was 0.58, but this reduction was not statistically or clinically significant. Only 7 of 20 patients showed a mean urine pH of 5.5 or less (acidic) during treatment with ascorbic acid. The study suggests that an ascorbic acid dosage of 1 g four times daily should not be used to maintain an acidic urinary pH for control of urinary tract infections in patients with spinal cord injuries.

Topics: Adolescent; Adult; Ascorbic Acid; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Spinal Cord Injuries; Urinary Bladder, Neurogenic; Urinary Catheterization; Urinary Tract Infections; Urine

Topics: 5-Methylcytosine; Animals; Ascorbic Acid; Axons; Contusions; Dioxygenases; Epigenesis, Genetic; Female; Motor Cortex; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries

In recent years, systemic hypothermia has taken the spotlight for its use in spinal cord injury (SCI) research fields, but detailed molecular mechanisms are still not fully understood. In this study, we use an online-electrochemical system (OECS) to in vivo continuously monitor the ascorbate of the rats' spinal cord. We find that the basal level of ascorbate in rat spinal cord is 1.85 ± 0.88 μmol L

Topics: Acute Disease; Animals; Ascorbic Acid; Extracellular Space; Hypothermia, Induced; Male; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries

Recently we reported that fluoxetine (10 mg/kg) improves functional recovery by attenuating blood spinal cord barrier (BSCB) disruption after spinal cord injury (SCI). Here we investigated whether a low-dose of fluoxetine (1 mg/kg) and vitamin C (100 mg/kg), separately not possessing any protective effect, prevents BSCB disruption and improves functional recovery when combined. After a moderate contusion injury at T9 in rat, a low-dose of fluoxetine and vitamin C, or the combination of both was administered intraperitoneally immediately after SCI and further treated once a day for 14 d. Co-treatment with fluoxetine and vitamin C significantly attenuated BSCB permeability at 1 d after SCI. When only fluoxetine or vitamin C was treated after injury, however, there was no effect on BSCB disruption. Co-treatment with fluoxetine and vitamin C also significantly inhibited the expression and activation of MMP-9 at 8 h and 1 d after injury, respectively, and the infiltration of neutrophils (at 1 d) and macrophages (at 5 d) and the expression of inflammatory mediators (at 2 h, 6 h, 8 h or 24 h after injury) were significantly inhibited by co-treatment with fluoxetine and vitamin C. Furthermore, the combination of fluoxetine and vitamin C attenuated apoptotic cell death at 1 d and 5 d and improved locomotor function at 5 weeks after SCI. These results demonstrate the synergistic effect combination of low-dose fluoxetine and vitamin C on BSCB disruption after SCI and furthermore support the effectiveness of the combination treatment regimen for the management of acute SCI.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood-Brain Barrier; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Fluoxetine; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Recovery of Function; Selective Serotonin Reuptake Inhibitors; Spinal Cord; Spinal Cord Injuries

Spinal cord injury [SCI] leads to complex cellular and molecular interactions which affects various organ systems. The present study focused on determining the protection offered by Vitamin C against spinal injury-induced kidney damage in wistar rats. The experimental protocol was performed with three groups; Sham, SCI and Vitamin C [20 mg/kg/bw] followed by SCI. The kidney tissue was investigated for oxidative stress parameters [reactive oxygen species, protein carbonyl, sulphydryl content, thiobarbituric acid reactive species [TBARS], and myeloperoxidase activity] and antioxidant status [glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase activity]. Further, inflammation studies were performed by analyzing expression of NF-κB, cycloxygenase-2, iNOS through western blot analysis and inflammatory cytokines by TNF-α and IL-1β levels. The present study shows clear evidence that Vitamin C treatment abrogated spinal injury-induced oxidative stress and inflammatory responses and enhanced the antioxidant status. Thus, the protection offered by Vitamin C against spinal cord injury-induced kidney damage is attributed to its anti-oxidant and anti-inflammatory effects.

Topics: Animals; Antioxidants; Ascorbic Acid; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Down-Regulation; Glutathione; Laminectomy; Male; NF-kappa B; Nitric Oxide Synthase Type II; Peroxidase; Protein Carbonylation; Rats; Rats, Wistar; Reactive Oxygen Species; Retinal Diseases; Spinal Cord Injuries

Experimental, controlled, animal study.. To assess the effects of vitamins C and E (VCE) treatment on oxidative stress and programmed cell deaths after rat spinal cord injury (SCI), as well as functional recovery.. Taiwan.. Fifty-four Sprague-Dawley rats were used for the experimental procedure. In the sham group, laminectomy at T10 was performed, followed by impactor contusion of the spinal cord. In the control group, only a laminectomy was performed without contusion. Oxidative stress status was assessed by measuring the spinal cord tissue content of superoxide dismutase (SOD) and gluthatione peroxidase (GSH-Px) activities. We also evaluated the effects of combined VCE treatment using western blot to analyze expression of cleaved caspase-3 and microtubule-associated protein light chain 3 (LC3), and the Basso, Beattie and Bresnahan (BBB) scale to evaluate functional outcomes.. Combined treatment of VCE significantly counteracted the effects of spinal cord contusion on oxidative stress represented by activities of SOD and GSH-Px (P<0.05). The VCE treatment also significantly enhanced LC3-II expression and decreased cleaved caspase-3 compared with the sham (P<0.05). Furthermore, BBB scores significantly improved in the VCE-treated group compared with the sham group (on day 14 and 28 after SCI; P<0.05).. The combined administration of VCE was clearly capable of modulating the antioxidant effects, and of reducing apoptosis and increasing autophagy at the lesion epicenter leading to an improved functional outcome. Use of such clinically ready drugs could help earlier clinical trials in selected cases of human SCIs.

Topics: Animals; Antioxidants; Apoptosis; Ascorbic Acid; Blotting, Western; Disease Models, Animal; Female; Oxidative Stress; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord Injuries; Vitamin E

To evaluate the effects of different doses of ascorbic acid (AA) on the functional performance of rats subjected to standardized spinal cord injury (SCI).. Thirty female Sprague-Dawley rats were divided into three groups (10 animals in each group): control group: rats were subjected to SCI injury and received intraperitoneal saline administration; normal-dose AA group: rats were subjected to SCI injury and received daily intraperitoneal administration of AA at 100 mg kg(-1) bodyweight; high-dose AA group: rats were subjected to SCI injury and received daily intraperitoneal administration of AA at 200 mg kg(-1) bodyweight. The Basso, Beattie, Bresnahan Locomotor Rating Score (BBB score) and footprint analysis were performed to evaluate the functional performance of the rats in each group, and hematoxylin and eosin staining was performed to evaluate necrosis at the injury site.. At days 14 and 28 after SCI, rats in the high-dose AA group, but not the normal-dose AA group, exhibited significantly better BBB score compared with the control group (P<0.05). Compared with the control and normal-dose AA group, the high-dose AA group also showed increased stride length, decreased stride width and reduced toe dragging (P<0.05). Histological analysis revealed that both the normal- and high-dose AA groups had reduced necrosis in the injury site compared with the control group (P<0.05).. High-dose AA administration during the acute phase post SCI significantly reduced secondary injury-induced tissue necrosis and improved functional performance in rats.

Topics: Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Injections, Intraperitoneal; Locomotion; Psychomotor Performance; Rats; Rats, Sprague-Dawley; Recovery of Function; Severity of Illness Index; Spinal Cord Injuries; Time Factors

A total of 30 female Sprague-Dawley rats (180-220 g) subjected to spinal cord injury (SCI) were divided into three groups of ten rats each. Group 1 served as control (SCI + Saline), Group 2 received daily dose of ascorbic acid 2,000 mg/kg body weight and group 3 rats received alpha tocopherol daily with the dose of 2,000 mg/kg body weight for 14 days. The Spontaneous coordinate activity (SCA), Basso, Beattie, and Bresnahan (BBB) and Tarlov locomotor scores were used to assess functional recovery of SCI rats. Compared to group 1, group 2 showed statistically insignificant improvement in the SCA, BBB and Tarlov scores at the end of the study. Compared to group 1, group 3 showed statistically significant improvement in the SCA (P < 0.001), BBB (P < 0.001) and Tarlov (P < 0.01) scores at the end of the study. In conclusion, the administration of alpha-tocopherol enhances the reparative effects against SCI and it is more effective than ascorbic acid.

Topics: alpha-Tocopherol; Analysis of Variance; Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Drug Administration Routes; Female; Locomotion; Rats; Rats, Sprague-Dawley; Recovery of Function; Severity of Illness Index; Spinal Cord Injuries; Time Factors

Some studies have made use of the antioxidative capabilities of high doses of vitamins C and E with the aim of neutralizing the noxious effects of free radicals following spinal cord lesion.. To evaluate the effects of vitamins C and E, separately and together, on the functional performance of rats that were subjected to standardized spinal cord contusion.. Forty male Wistar rats were used, divided into four groups of 10 animals each. Group 3 received vitamin C 100 mg kg(-1) day(-1) intraperitoneally; Group 2 received vitamin E 100 mg kg(-1) day(-1) orally; Group 1 received vitamins C and E, at the same dosages; and Group 4 was the control. The vitamin therapy was administered for 1 month and then the animals were killed. A direct contusional injury was caused and functional evaluation was performed using the Basso, Beattie and Bresnahan rating scale. The rats were evaluated on the second postoperative day and weekly thereafter, until the end of the experiment.. The results were evaluated by means of the one-tailed, non-paired and non-parametric Mann-Whitney test, comparing the groups two by two. No significant difference in functional performance was observed between the groups.. The use of vitamins C and E in these rats did not improve their neurological performance. However, histopathological examination showed that the inflammatory response was less intense following administration of the combination of vitamins C and E.

Topics: Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Laminectomy; Male; Rats; Rats, Wistar; Spinal Cord Injuries; Vitamin E

Ascorbic acid plays important roles in mammalian central nervous system. We employed an on-line analytical system to monitor the extracellular ascorbic acid concentrations in anesthetized rat spinal cord before and after the experimental injury. A microdialysis probe (216 microm od, 200 microm id, 3 mm in length) was implanted into an anesthetized rat spinal cord (Thoratic-12). Microdialysis perfusate (2 microl/min) was collected in the sample loop (20 microl) of an on-line injector for direct injection onto a High Performance Liquid Chromatography (HPLC) system equipped with an electrochemical detector. Normal ascorbic acid concentrations in the spinal cord extracellular fluids ranged from 1.8 microM to 10.8 microM (mean +/- S.D. 5.6 +/- 2.4 microM, n = 8). The experimental spinal cord injury, induced by a lesion at T-10, gradually yet significantly increased the extracellular ascorbic acid levels. The effect of exogenous glutamate perfusion (0.2 mM, 2 mM, and 20 mM) through the microdialysis probe also increased the extracellular ascorbic acid concentrations in a dose dependent manner. These results suggested that the injury-induced ascorbic acid accumulation may result from elevated extracellular glutamate levels that are commonly observed in spinal cord injury. This on-line, continuous and automatic monitoring system can be applied to future investigations on the roles of ascorbic acid in spinal cord injuries.

Topics: Anesthesia; Animals; Ascorbic Acid; Extracellular Space; Glutamic Acid; Male; Microdialysis; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries

To investigate the therapeutic effect of high-dose Vitamin C on acute spinal cord injury (SCI) in rats.. Forty-eight SD rats were randomly divided into 3 groups (A, B, C), and SCI was made by Allen's Mode (7 g x 4 cm) on spinal cord T11 extradurally. Half an hour after SCI, the rats of groups A and B were given methylprednosolone (30 mg/kg, i.p.) and Vitamin C (200 mg/kg, i.p.) respectively. The rats of Group C recevied normal saline i.p. only. The results of hematoxylin staining+Olsiwski corpuscle staining and the moisture of spinal cord 48 h after SCI were observed. Inclined plate and Gale scale were observed 2 weeks after SCI.. In both group A and group B, there was less scope of neuro-necrosis and bleeding, less degree of hydrops and more Olsiwski corpuscle count in neure of injured areas 48 h after injury, and much better behavioral assessment (inclined plate+Gale scale) 2 weeks after injury in comparison with those in group C (P<0.05), while there were no diffferences between group A and group B statistically (P>0.05).. Early administration of high-dose Vitamin C is effective for treating SCI, but its effectiveness is not superior to that of high-dose methylprednisolone.

Topics: Animals; Ascorbic Acid; Female; Free Radical Scavengers; Male; Methylprednisolone; Neuroprotective Agents; Random Allocation; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries

To determine serum levels of vitamins A, C, and E among individuals with spinal cord injury (SCI) living in the community, to compare these levels with general population norms, and to assess their association with demographic and injury-related data (age at onset, time since onset, level and completeness of injury), function, nutritional behaviors, and health status.. Descriptive and correlational.. General community.. A total of 110 adults (> or =18y) with traumatic SCI of at least 2 years in duration living within a 13-county area in Texas.. Not applicable.. Demographic information, age at onset, time since onset, American Spinal Injury Association (ASIA) total motor index score, ASIA impairment score, assay of serum vitamins, FIM trade mark instrument motor items, Health-Promoting Lifestyle Profile nutrition subscale, Medical Outcomes Study 36-Item Short-Form Health Survey general health subscale, and pressure ulcer occurrence in past 12 months.. Many (16%-37%) of the participants had serum levels below the reference range for each vitamin. Being older at onset or less impaired was associated with higher serum vitamin A levels. Higher levels of serum vitamin A also were related to better function and health status and with not having a pressure ulcer within the past 12 months. Being older or older at onset was associated with higher serum levels of vitamin E. No relationships with vitamin C were found.. Vitamin levels may be related to function, general health, and pressure ulcer incidence in persons with SCI. Further study is needed to determine effective interventions to improve vitamin levels and determine the effect of such improvements on overall health and rehabilitation outcomes.

Topics: Activities of Daily Living; Adult; Age Factors; Age of Onset; Aged; Aged, 80 and over; Ascorbic Acid; Feeding Behavior; Female; Health Status; Humans; Incidence; Life Style; Male; Middle Aged; Nutrition Surveys; Nutritional Status; Pressure Ulcer; Risk Factors; Spinal Cord Injuries; Texas; Time Factors; Vitamin A; Vitamin E

A study in which levels of lipid peroxidation were measured, the thiobarbituric acid-reactive substances were estimated in an experimental rat model, and the recovery was assessed.. To ascertain the occurrence of thiobarbituric acid-reactive substances in the damaged spinal cord, and to investigate the effectiveness of a hydroxyl radical scavenger EPC-K1, a phosphate diester linkage of vitamins E and C, in attenuating the severity of spinal cord injury.. Lipid peroxidation has been reported to play an important role in spinal cord injury. There is no report on the use of EPC-K1 to attenuate the severity of spinal cord injury in either animal or human studies.. Spinal cord injury was induced by placing a 25-g weight on T12, and the animals were divided into six groups. Group 1 (sham) received only laminectomy. Group 2 (control) received spinal cord injury. Group 3 received EPC-K1 5 minutes before injury. Group 4 received it 5 minutes after injury. Group 5 received it 3 hours after injury. Group 6 received it five times, respectively: at 5 minutes, then 1, 2, 3, and 4 hours after injury. The levels of thiobarbituric acid-reactive substances were measured in the spinal cord, and the recovery was assessed.. The thiobarbituric acid-reactive substances content increased after injury, with two peaks, at 1 and 4 hours. Concentration at the 4-hour peak was lower in nitrogen mustard-induced leukocytopenia rats than in the control rats. The EPC-K1 injection reduced thiobarbituric acid-reactive substances content at 1 and 4 hours after injury in Group 3 (respectively, 34.3% and 42.7% vs. control) and only that at 4 hours in Group 6 (24.9% vs. control). Motor function recovery and histologic findings were better in these two groups than in Group 2.. Repeated injection of EPC-K1 attenuated the severity of spinal cord injury.

Topics: Alkylating Agents; Animals; Ascorbic Acid; Free Radical Scavengers; Leukocyte Count; Lipid Peroxidation; Male; Mechlorethamine; Motor Activity; Rats; Rats, Wistar; Spinal Cord Injuries; Statistics, Nonparametric; Thiobarbituric Acid Reactive Substances; Vitamin E

Generation of free radicals and subsequent lipid peroxidation have been proposed to contribute to delayed tissue damage following traumatic spinal cord injury (SCI). Ubiquinols (reduced coenzyme Q), ascorbate (vitamin C), and alpha-tocopherol (vitamin E) are endogenous antioxidants; decreases in tissue levels of these compounds may, therefore, reflect ongoing oxidative reactions. In the present studies, alterations in tissue levels of ubiquinol-9 and -10, ascorbate, and alpha-tocopherol were examined after SCI of varying severity in the rat. Levels of alpha-tocopherol did not change significantly after injury. Ascorbate and ubiquinol levels were decreased after trauma. Changes in tissue levels of ubiquinol, but not ascorbate reflected the degree of trauma. Thus, ubiquinol levels may provide a useful marker of the oxidative component of the secondary injury response.

Topics: Animals; Antioxidants; Ascorbic Acid; Male; Rats; Rats, Inbred Strains; Spinal Cord Injuries; Ubiquinone; Vitamin E

The development of permanent paraplegia in spinal injured cats is accompanied by a large progressive decline in total ascorbic acid (AA) and a transient increase in oxidized (AAox) ascorbate. Since AA is involved in a variety of processes required for normal central nervous system (CNS) performance we suggested that such large ascorbate loss may contribute to derangements in spinal cord function following injury. We now demonstrate that methylprednisolone (15 mg/kg) and naloxone (10 mg/kg), two treatments that preserve neurologic function in this model, rapidly block deteriorating ascorbate status. Naloxone at 1 mg/kg, a treatment providing no therapeutic benefit, has no protective effect on ascorbate. The results strongly support the hypothesis that loss of ascorbate homeostasis reflects irreversible loss of neurologic function following spinal cord injury.

Topics: Animals; Ascorbic Acid; Cats; Disease Models, Animal; Homeostasis; Locomotion; Methylprednisolone; Naloxone; Paraplegia; Spinal Cord Injuries; Time Factors

To achieve effective suppression of bacteriuria in spinal cord injured (SCI) patients, methenamine mandelate and methenamine hippurate are commonly given with ascorbic acid. Since the effectiveness of ascorbic acid as a urinary acidifier has been challenged and as it also has been suggested that methenamine salts do not produce effective urine formaldehyde concentrations in patients with indwelling urethral catheters, we studied two groups of SCI patients to determine (1) the effect of ascorbic acid on urine pH and formaldehyde concentration when administered with methenamine salts; (2) the effect of an indwelling urethral catheter versus intermittent catheterization on formaldehyde concentration in the urine of SCI patients taking methenamine salts; and (3) the relative urine formaldehyde concentrations produced by treatment with methenamine mandelate and methenamine hippurate in SCI patients. Methenamine mandelate produced significantly higher urine formaldehyde concentrations than did methenamine hippurate, especially among patients with intermittent catheterization. Ascorbic acid produced a significant effect on urine pH but not on formaldehyde concentration.

Topics: Anti-Infective Agents, Urinary; Ascorbic Acid; Bacteriuria; Formaldehyde; Hippurates; Humans; Hydrogen-Ion Concentration; Mandelic Acids; Methenamine; Spinal Cord Injuries

Feline spinal cord contains 0.97 mM ascorbic acid, as measured by the dinitrophenylhydrazine method. Greater than 90% is maintained in the reduced form. When functioning normally, the CNS conserves its ascorbic acid with a turnover rate of 2% per h. Following contusion injury severe enough to produce paraplegia, ascorbic acid is rapidly lost from injured spinal tissue. Thus, ascorbic acid is decreased 30% by 1 h and 50% by 3 h following injury. Oxidized ascorbic acid is increased at 1, but not 3, h following impact. As a consequence of its many functions in CNS, loss of ascorbic acid may contribute to derangements in spinal cord function following injury.

Topics: Animals; Ascorbic Acid; Brain; Cats; Kinetics; Oxidation-Reduction; Spinal Cord; Spinal Cord Injuries

Topics: Anti-Infective Agents, Urinary; Ascorbic Acid; Humans; Hydrogen-Ion Concentration; Mandelic Acids; Methenamine; Spinal Cord Injuries

The hypothesis that pathologic free-radical reactions are initiated and catalyzed in the major central nervous system (CNS) disorders has been further supported by the current acute spinal cord injury work that has demonstrated the appearance of specific, cholesterol free-radical oxidation products. The significance of these products is suggested by the fact that: (i) they increase with time after injury; (ii) their production is curtailed with a steroidal antioxidant; (iii) high antioxidant doses of the steroidal antioxidant which curtail the development of free-radical product prevent tissue degeneration and permit functional restoration. The role of pathologic free-radical reactions is also inferred from the loss of ascorbic acid, a principal CNS antioxidant, and of extractable cholesterol. These losses are also prevented by the steroidal antioxidant. This model system is among others in the CNS which offer distinctive opportunities to study, in vivo, the onset and progression of membrane damaging free-radical reactions within well-defined parameters of time, extent of tissue injury, correlation with changes in membrane enzymes, and correlation with readily measurable in vivo functions.

Topics: Animals; Ascorbic Acid; Cats; Central Nervous System Diseases; Chemical Phenomena; Chemistry; Cholesterol; Free Radicals; Methylprednisolone; Microcirculation; Oxidation-Reduction; Spinal Cord Injuries

Topics: Adult; Ascorbic Acid; Chemical Phenomena; Chemistry; Cyanides; Dose-Response Relationship, Drug; False Negative Reactions; Humans; Hydrogen-Ion Concentration; Intrinsic Factor; Male; Middle Aged; Spinal Cord Injuries; Urine; Vitamin B 12

The intermittent bladder catheterization technique has been proposed as an effective way of eliminating the need for an inlying. Foley catheter in patients with neurovesical dysfunction following spinal cord injury. In the study reported here, a group of 41 male patients with spinal cord injuries achieved a catheter-free state with this method. Of these 41 patients, 19 have been followed for 1 year. Data obtained from the 19 patients are presented here for comparison with data from other recent studies. In the present study, the patients' fluid intake was restricted to 2,000 cc daily. A detrusor reflex was triggered by lower abdominal percussion followed by a Credé maneuver. A 6-hour catheterization schedule was used unless autonomic dysreflexia required more frequent catheterizations. Ascorbic acid, methenamine mandelate and nitrofurantoin were routinely administered, and specific antibiotics were also given following trial off-catheter, depending on the results of urine cultures and sensitivity studies. All patients achieved a catheter-free state in an average time of 17.1 days; no late failures have occurred. Two patients developed vesicoureteral reflux, but no evidence of hydronephrosis was observed. At 1 year only 16% of the patients were found to have infected urine, as compared to 100% at initiation of the trial off-catheter.

Topics: Ascorbic Acid; Female; Follow-Up Studies; Humans; Methenamine; Nitrofurantoin; Spinal Cord Injuries; Time Factors; Urinary Bladder, Neurogenic; Urinary Catheterization; Urinary Tract Infections; Urine

Topics: Angiography; Animals; Ascorbic Acid; Blood Vessels; Cats; Female; Humans; Intervertebral Disc; Male; Methenamine; Motor Neurons; Myelography; Nerve Tissue; Neuroradiography; Paraplegia; Pressure; Quadriplegia; Rabbits; Spinal Canal; Spinal Cord Compression; Spinal Cord Injuries; Spinal Cord Neoplasms; Urinary Catheterization; Urinary Tract Infections; Urination Disorders; Urologic Diseases

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Bethanechol Compounds; Humans; Male; Methenamine; Middle Aged; Paraplegia; Parasympathomimetics; Spinal Cord Injuries; Urinary Catheterization; Urinary Tract Infections; Urine