Loss of Ascorbic Acid from Injured Feline Spinal Cord

Pietronigro, Dennis; Hovsepian, Movses; Demopoulos, Harry B.; Flamm, Eugene S.

doi:10.1111/j.1471-4159.1983.tb09053.x

Cited by 61 publications

(14 citation statements)

References 47 publications

(49 reference statements)

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“…Others have confirmed that MDA levels increase in the first 2 h [15]. An increase in LP that appears in the injured cord within the first hour has also been evidenced in terms of a depletion of endogenous antioxidants, including ascorbic acid [16], alpha-tocopherol (also known as vitamin E) [17], glutathione [18], and ubiquinol-9 and ubiqunol-10 [19]. More contemporary immunohistochemical and immunoblotting methods have been recently used, which reveals an impressive increase in the levels of the LP-derived aldehydic breakdown products 4-HNE [20][21][22][23] and acrolein [24,25].…”

Section: Increased Lipid Peroxidationmentioning

confidence: 80%

“…Although hemoglobin itself has been reported to stimulate oxygen radical reactions, it is more likely that iron released from hemoglobin is responsible for hemoglobin-mediated oxidative damage [4,5]. Iron is released from hemoglobin by H 2 O 2 or by lipid hydroperoxides (LOOH; see as follows) [16], and this release is further enhanced as the pH falls to 6.5 or below. Each of the PN-derived radicals (•OH, •NO 2 , and •CO 3 ) can initiate LP cellular damage by abstraction of an electron from a hydrogen atom bound to an allylic carbon in polyunsaturated fatty acids or can cause protein carbonylation by reaction with susceptible amino acids (e.g., lysine, cysteine, arginine).…”

Section: Iron-dependent Hydroxyl Radical Formationmentioning

confidence: 99%

“…Although this tripartite LOO• antioxidant defense system (vit E, vitamin C, GSH) works fairly effectively in the absence of a major post-traumatic oxidative stress, studies have shown that each of these antioxidants is rapidly consumed during the early minutes and hours after SCI [16][17][18]. Thus, it has long been recognized that more effective pharmacological LOO• and LO• scavengers are needed than what endogenous biochemistry has provided.…”

Section: Overview Of Antioxidant Mechanistic Approachesmentioning

confidence: 99%

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Antioxidant Therapies for Acute Spinal Cord Injury

2011

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Summary:One of the most investigated molecular mechanisms involved in the secondary pathophysiology of acute spinal cord injury (SCI) is free radical-induced, iron-catalyzed lipid peroxidation (LP) and protein oxidative/nitrative damage to spinal neurons, glia, and microvascular cells. The reactive nitrogen species peroxynitrite and its highly reactive free radicals are key initiators of LP and protein nitration in the injured spinal cord, the biochemistry, and pathophysiology of which are first of all reviewed in this article. This is followed by a presentation of the antioxidant mechanistic approaches and pharmacological compounds that have been shown to have neuroprotective properties in preclinical SCI models. Two of these, which act by inhibition of LP, are high-dose treatment with the glucocorticoid steroid methylprednisolone (MP) and the nonglucocorticoid 21-aminosteroid tirilazad, have been demonstrated in the multicenter NASCIS clinical trials to produce at least a modest improvement in neurological recovery when administered within the first 8 hours after SCI. Although these results have provided considerable validation of oxidative damage as a clinically practical neuroprotective target, there is a need for the discovery of safer and more effective antioxidant compounds for acute SCI.

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Section: Increased Lipid Peroxidationmentioning

confidence: 80%

Section: Iron-dependent Hydroxyl Radical Formationmentioning

confidence: 99%

Section: Overview Of Antioxidant Mechanistic Approachesmentioning

confidence: 99%

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Antioxidant Therapies for Acute Spinal Cord Injury

2011

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“…For example, decreased brain concentrations of AA were observed in animal models of focal cerebral ischemia, 21,22 and tissue levels of AA and ␣-tocopherol were decreased after spinal cord impact trauma in several species. 23 In rats, transient cerebral ischemia and reperfusion caused ROS production associated with consumption of ubiquinol-9 and ubiquinol-10.…”

Section: Discussionmentioning

confidence: 99%

Plasma Vitamin C Levels Are Decreased and Correlated With Brain Damage in Patients With Intracranial Hemorrhage or Head Trauma

Polidori

Mecocci

Frei

2001

Stroke

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Background and Purpose-Free radical hyperproduction may play an important role in brain hemorrhage and ischemia/reperfusion injury. The aims of this study were to assess whether antioxidant depletion occurs after intracranial hemorrhage (ICH) and head trauma (HT) and to evaluate the relation between the diameter of the brain lesion, the degree of the neurological impairment, and any observed antioxidant changes. Methods-We measured plasma levels of vitamin C (ascorbic acid, AA), uric acid (UA), vitamin E (␣-tocopherol), and ubiquinol-10 in 13 patients with ICH and 15 patients with HT on the day of the brain injury and subsequently every other day up to 1 week. Patients were compared with 40 healthy control subjects. Results-ICH and HT patients had significantly lower plasma levels of AA compared with healthy subjects, in contrast to plasma levels of UA, ␣-tocopherol, and ubiquinol-10. AA levels were significantly inversely correlated with the severity of the neurological impairment as assessed by the Glasgow Coma Scale and the National Institutes of Health Stroke Scale. AA levels were also significantly inversely correlated with the major diameter of the lesion. In addition, mean plasma AA levels were lower in jugular compared with peripheral blood samples obtained from 5 patients. Conclusions-These findings suggest that a condition of oxidative stress occurs in patients with head trauma and hemorrhagic stroke of recent onset. The consequences of early vitamin C depletion on brain injury as well as the effects of vitamin C supplementation in ICH and HT patients remain to be addressed in further studies. Key Words: antioxidants Ⅲ brain hemorrhage Ⅲ head trauma Ⅲ oxidative stress Ⅲ vitamin C I ncreased production of free radicals and reactive oxygen species (ROS) leading to oxidative stress 1 appears to play an important role in the pathogenesis of ischemic, 2,3 hemorrhagic, 4,5 and traumatic brain injury. 6,7 Studies in animal models of focal cerebral ischemia and reperfusion have demonstrated the presence of increased levels of ROS. 8 -11 ROS also probably contribute to brain injury in head trauma (HT) and intracranial hemorrhage (ICH) in humans, because hemorrhage is associated with the release of hemoglobinbound heme iron, which can participate in free radical reactions to produce ROS. 4,5,12 One possible consequence of excess ROS formation is lipid peroxidation. The brain appears to be particularly vulnerable to oxidative lipid damage because of its high content of polyunsaturated fatty acids. 13 Lipid peroxidation may alter the fluidity and permeability of neuronal membranes and thus, cellular functioning, or damage membranebound receptors and enzymes. 13 In brain hemorrhage, the presence of "free" iron 14 may favor the conversion of lipid hydroperoxides to lipid alkoxyl radicals, which can "reinitiate" lipid peroxidation and hence further expand the radical chain reaction. 13 In addition, tissue lactic acidosis can dramatically enhance ROS formation and lipid peroxidation in brain tissue, which in turn ca...

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“…It also participates in the elimination of oxygen free radicals. 7 We believe that administration of high doses of antioxidants that are naturally present in the organism (vitamins C and E) may have protective effects with regard to spinal cord injury. This may be achieved without presenting the side effects that are found in some classes of drugs, particularly glucocorticoids.…”

Section: Introductionmentioning

confidence: 99%

Antioxidative therapy in contusion spinal cord injury

et al. 2008

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Introduction: 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. Objectives: 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. Materials and methods: Forty male Wistar rats were used, divided into four groups of 10 animals each. Group 3 received vitamin C 100 mg kg À1 day À1 intraperitoneally; Group 2 received vitamin E 100 mg kg À1 day À1 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. Results: The results were evaluated by means of the one-tailed, non-paired and non-parametric

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Loss of Ascorbic Acid from Injured Feline Spinal Cord

Cited by 61 publications

References 47 publications

Antioxidant Therapies for Acute Spinal Cord Injury

Antioxidant Therapies for Acute Spinal Cord Injury

Plasma Vitamin C Levels Are Decreased and Correlated With Brain Damage in Patients With Intracranial Hemorrhage or Head Trauma

Antioxidative therapy in contusion spinal cord injury

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