The Effect of Age, Growth Retardation and Asphyxia on Ascorbic Acid Concentrations in Developing Brain

Adlard, B. P. F.; Souza, S W De; Moon, Susan

doi:10.1111/j.1471-4159.1973.tb07532.x

Cited by 54 publications

(22 citation statements)

References 13 publications

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“…USA 88 (1991) 11161 against ischemic injury, since depletion of brain GSH with buthionine sulfoximine, a selective inhibitor for -t-glutamylcysteine synthetase, increased postischemic infarct size and edema. As in other tissues, ascorbic acid exists almost exclusively in its reduced form in brain (>99%) (2,8,33). It has also been reported that AH2 decreases significantly following cerebral ischemia and head injury.…”

Section: Methodsmentioning

confidence: 96%

Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase.

Kinouchi

Epstein

Mizui

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

542

244

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Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischeria 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 ischemla. 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 transgeic mice bearing the human SODI 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 s ntly decreased in trenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemlc hemisphere, -but levels-in surrounding cortex and striaturm were gficantly higher in trasgenic'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.The role of oxygen free radicals in the pathogenesis of infarction and edema following cerebral ischemia has been intensively investigated since the report of Flamm et al. (1).Because of technical 4ffficulties in the measurement of free radicals'in brain tissues the part played by free radicals in the pathogenesis of cerebral ischemia still remains unclear (2, 3). However, reports of decreased levels of lipid-soluble and water-soluble endogenous antioxidants and of increased levels ofconjugated dienes and lipid peroxidation (4-10) support the notion that free radicals are involved in ischemic brain injury.Indirect methods using specific antioxidants [e.g., superoxide dismutase (SOD) and catalase] have traditionally been used to implicate oxygen free radicals in physiological or pathological processes. Unfortunately, the half-life of CuZn-SOD in circulating blood is extremely short (6 min), and it is unable to pass the blood-brain barrier. Therefore, use has been made of chemically modified enzymes for work on cerebral injury (11), and it has been found that polyethylene glycol-conjugated CuZn-SOD (PEG-SOD) and PEG-catalase reduce the degree of cortical infarction resulting from focal cerebral ischemia (12). Similarly, CuZn-SOD conjugated with divinyl ether/maleic acid copolymer ameliorated delayed hippocampal neuronal death after global cerebral ischemia in the gerbil brain (13). Liposome-entrapped CuZn-SOD, which has a half life of 4.2 hr (11), reduces the severity of traumatic and ischemic injuries (14,15).Although these studies provide potential therapeutic precedents for the management of brain in...

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Section: Methodsmentioning

confidence: 96%

Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase.

Kinouchi

Epstein

Mizui

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

542

244

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“…Data are mean 2~ SEM; OB olfactory bulb, CTX cortex, DVR dorsal ventricular ridge, CB cerebellum, OL optic lobe, BS brainstem, SC spinal cord, ON optic nerve, HP hippocampus, SC superior colliculus (modified from Rice et al, 1995). 1992), have a key role in preventing oxidative damage during reoxygenation after a hypoxic dive. Intriguingly, ascorbate is also high in neonatal rats (Adlard et al, 1973;Allison and Stewart, 1973;Rice and Russo-Menna, 1998), which also have greater tolerance of anoxia than do adults (Kabat, 1940;Xia et al, 1992). As di,;cussed more fully below, high brain ascorbate levels in neonatal rats reflect the predominance of h!igh-ascorbate neurons in rat CNS before the later proliferation of low-ascorbate glial cells (Rice and RussoMenna, 1998).…”

Section: Ascorbate a N D Gsh As Antioxidantsmentioning

confidence: 94%

Ascorbate compartmentalization in the CNS

Rice

1999

neurotox res

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Ascorbic acid, found physiologically as the ascorbate anion, is an abundant water-soluble antioxidant. It is concentrated in the intracellular compartment of all tissues in the body. The CNS has particularly high levels of ascorbate. Recent data from this laboratory indicate that ascorbate is distinctly compartmentalized between neurons and glia, with an average intracellular concentration of 10 mM in neurons and 1 mM in glial cells. These data can be contrasted with those for another important low molecular weight antioxidant, glutathione, which is somewhat more concentrated in glia than in neurons. The present review summarizes evidence for ascorbate compartmentalization between neurons and glia and considers these data in light of evidence for the roles of ascorbate as a neuroprotective antioxidant and as a neuromodulator in the CNS.

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“…It is believed that in fetal and newborn animals the levels are somewhat higher (24)(25)(26). Thus, aqueous brain extracts contain sufficient amounts of ascorbic acid to account for their ability to induce AcChoR accumulation in vitro.…”

Section: Methodsmentioning

confidence: 99%

Ascorbic acid mediates acetylcholine receptor increase induced by brain extract on myogenic cells.

Knaack¹,

Podleski²

1985

Proc. Natl. Acad. Sci. U.S.A.

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Extracts of fetal calf brain cause a 3-to 5-fold increase in acetylcholine receptors (AcChoR) on cultured myogenic L5 cells. Purification of the substance causing the major portion of this receptor increase has been completed. Ultraviolet spectral characteristics, nuclear magnetic resonance, mass spectra, and AcChoR induction by the active factor are the same as those of commercially available ascorbic acid. The biological activity of ascorbic acid is not mimicked by reducing agents with or without sullhydryl groups. Compounds related to ascorbic acid were tested for their ability to induce AcChoR increases on L5 cells. D-Isoascorbic acid is the only substance with identical biological activity to ascorbic acid. Dehydroascorbic acid and ascorbic acid 2-0-sulfate also induce AcChoR increases but with lower specific activity. These data show that ascorbic acid can play a role in regulating AcChoR expression in myogenic tissue, and the presence of ascorbic acid in the purified fraction from fetal calf brain accounts for its ability to increase AcChoR in L5 cells.A major effect of coculturing rat spinal cord explants with L6 myogenic cells is an increase in the average site density of acetylcholine receptors (AcChoR) on the differentiated myotubes. The increase in receptor site density on myotubes adjacent to the explant is greater than that occurring on myotubes a few millimeters away. This graded distribution has been taken as an indication of the release, from the explant, of a diffusible substance causing the receptor increase (1). Similar results have been obtained in cocultures derived from chicken embryos (2). In addition to the increase in receptor site density, there is also an increase in the number of AcChoR clusters in these cultures (1, 2).Since it appears that the effects on AcChoR clustering and site density may be caused by different substances (3), in the present study we directed our attention toward the overall increase in AcChoR. This effect is of interest because changes in average AcChoR site density also occur during muscle development in vivo (4). Shortly after the fusion of mononucleated myoblasts, AcChoR levels increase dramatically (5, 6), and then decrease following innervation (7,8). Denervation of adult skeletal muscle results in a return to preinnervation site densities (9-11). The purification and identification of a soluble factor capable of inducing AcChoR site density increases offers an approach to the study of in vivo AcChoR site density regulation and, possibly, the control of AcChoR synthesis as well.The effects of nerve explants on AcChoR site density in myogenic tissue can be mimicked by soluble extracts of fetal rat, chicken, or calf brain (1,(12)(13)(14). We have used the increase in total AcChoR on L5 cells caused by fetal calf brain extracts (14) as an assay for the purification of the active factor. The L5 (46) cell line has similar characteristics to the L6 cell line isolated by Yaffe (15). We report here the identification of the material from fetal calf brain ...

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The Effect of Age, Growth Retardation and Asphyxia on Ascorbic Acid Concentrations in Developing Brain

Cited by 54 publications

References 13 publications

Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase.

Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase.

Ascorbate compartmentalization in the CNS

Ascorbic acid mediates acetylcholine receptor increase induced by brain extract on myogenic cells.

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