Ascorbate attenuates the systemic kainate-induced neurotoxicity in the rat hippocampus

MacGregor, D. G.; Higgins, Michael J.; Jones, Paul A.; Maxwell, William L.; Watson, M. J.; Graham, David I.; Stone, T.W.

doi:10.1016/0006-8993(96)00362-9

Cited by 115 publications

(48 citation statements)

References 60 publications

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“…Within the brain, however, ascorbate levels are not homogenous; in humans, the highest levels are found in the hippocampus, amygdala, and hypothalamus (Hornig, 1975). Although the temporal window of neuroprotection owing to ascorbate treatment is considerably shorter than that reported for other protectants, such as dizocilpine or R-phenylisopropyladenosine MacGregor et al, , 1996, the protective activity of ascorbate under our experimental conditions might be the result of its strong ability to scavenge free radicals. Here, we reported that exogenous ascorbate prevents TMT-induced increases in neuronal degeneration in the hippocampus via the attenuation of oxidative stress during the early stages.…”

Section: Discussionmentioning

confidence: 65%

Ascorbate attenuates trimethyltin-induced oxidative burden and neuronal degeneration in the rat hippocampus by maintaining glutathione homeostasis

et al. 2005

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Section: Discussionmentioning

confidence: 65%

Ascorbate attenuates trimethyltin-induced oxidative burden and neuronal degeneration in the rat hippocampus by maintaining glutathione homeostasis

et al. 2005

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“…5). It has been suggested that excitotoxin-induced toxicity is partially mediated by oxidative stress (MacGregor et al, 1996;Matsuoka et al, 1998), and the glial cells in which HO-1 protein was induced may be resistant to oxidative stress. Overexpression of HO-1 may contribute to the resistance of glial cells to oxidative stress.…”

Section: Ho-1 Expression In the Nts Of Rats 13mentioning

confidence: 99%

Induction of Heme Oxygenase-1 Is Involved in Carbon Monoxide-Mediated Central Cardiovascular Regulation

Lu²,

Ho³

et al. 2006

J Pharmacol Exp Ther

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Carbon monoxide (CO) has been identified as an endogenous biological messenger in the brain. Heme oxygenase (HO) catalyzes the metabolism of heme to CO and biliverdin. Previously, we have shown the involvement of CO in central cardiovascular regulation, baroreflex modulation, and glutaminergic neurotransmission in the nucleus tractus solitarii (NTS) of rats. In this study, we examined which HO isoform could be induced after hemin injection in the NTS. We also investigated their in situ distributions in the NTS after induction. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure was monitored intra-arterially. Unilateral microinjection of hemin (1 nmol), a heme molecule cleaved by HO to yield CO, produced significant decrease in blood pressure and heart rate. These cardiovascular effects of hemin were attenuated by prior administration of HO inhibitor zinc protoporphyrin IX (ZnPPIX). Microinjection of hemin into NTS resulted in significant induction of HO-1 protein expression in situ. Pretreatment of ZnPPIX significantly inhibited the HO-1 induction after hemin injection. No significant changes of HO-2 expression were found after hemin injection and ZnPPIX pretreatment. The in situ inductions of the HO-1 protein expression were further confirmed to be in glial cells and neurons after hemin injections into the NTS. These results indicated HO-1 but not HO-2 might be responsible for the generation of CO and contribute to central control of cardiovascular effects.

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“…It is uncertain if the absence of efficacy was related to inadequacy of the dose administered. Although a dose of 30 mg kg À1 was neuroprotective in rats, 7 we used a dose of 100 mg kg À1 , as this dose has been shown to be safe in neonates without any pro-oxidant or hemolytic effects in preterm infants. 17 Our study population did not encounter any hemolytic side effects; however, using a bigger dose cannot be recommended until safety data at a bigger scale becomes available.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 In animal studies, systemic injection with low doses results in high concentrations of ascorbic acid in brain tissue and a significant neuroprotection against hypoxic ischemic encephalopathy (HIE). 7,8 Interleukin-1b (IL-1b), IL-6 and other cytokines are released in HIE, 9 and the treatment with recombinant IL-1 receptor antagonist (IL-1ra) attenuates neuronal damage in animal models. 10 Ibuprofen can inhibit the production of proinflammatory cytokines and oxyradicals, 11 and poses a long-lasting protective effect to the brain against global and focal ischemia in animals.…”

Section: Introductionmentioning

confidence: 99%

Ascorbic acid combined with ibuprofen in hypoxic ischemic encephalopathy: a randomized controlled trial

et al. 2009

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Objective: Free oxygen radicals and proinflammatory cytokines are important causes for brain injury in neonates with hypoxic ischemic encephalopathy (HIE). Our objectives were to test the hypothesis that a combination of antioxidants (ascorbic acid) and anti-inflammatory agents (ibuprofen) can ameliorate the brain injury in HIE and improve neurodevelopmental outcomes when given to term infants immediately after birth.Study Design: In a prospective, randomized, double-blinded controlled trial, 60 asphyxiated term infants were assigned to one of two groups, intervention and control. The intervention group (n ¼ 30) received intravenous ascorbic acid and oral ibuprofen for 3 days; and the control group (n ¼ 30) received similar volumes of a placebo. We measured a panel of cytokines at enrollment and administered the treatment drugs within 2 h after birth. Neurological evaluations and developmental screenings were performed for all survivors at 6 months of age.Result: The Intervention and Control groups did not differ in the severity of HIE at enrollment, the concentrations of IL-1b and IL-6, the incidence of mortality (37 vs 33%), the incidence of neurological abnormalities at hospital discharge (47 vs 55%) and the incidence of developmental delay at 6 months of age (32 vs 40%), respectively. None of the observed complications were related to intervention. Serum interleukin (IL)-1b and IL-6 concentrations correlated positively with the severity of HIE at birth (P<0.01), whereas only serum IL-6 correlated with neurodevelopmental outcome at 6 months (P<0.001).Conclusion: Early administration of ascorbic acid and ibuprofen did not affect outcomes in infants with perinatal asphyxia. This study does not explain whether our intervention was not effective in blocking free radicals and inflammatory cytokines, if the dosing and route of administration were inadequate, or if other mediators existed that could have a more powerful role in brain injury during hypoxia-ischemia.

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Ascorbate attenuates the systemic kainate-induced neurotoxicity in the rat hippocampus

Cited by 115 publications

References 60 publications

Ascorbate attenuates trimethyltin-induced oxidative burden and neuronal degeneration in the rat hippocampus by maintaining glutathione homeostasis

Ascorbate attenuates trimethyltin-induced oxidative burden and neuronal degeneration in the rat hippocampus by maintaining glutathione homeostasis

Induction of Heme Oxygenase-1 Is Involved in Carbon Monoxide-Mediated Central Cardiovascular Regulation

Ascorbic acid combined with ibuprofen in hypoxic ischemic encephalopathy: a randomized controlled trial

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