Effect of allopurinol on NMDA receptor modification following recurrent asphyxia in newborn piglets

Marro, Peter J.; Hoffman, David J.; Schneiderman, Roy; Mishra, Om P.; Delivoria‐Papadopoulos, Maria

doi:10.1016/s0006-8993(97)01453-4

Cited by 24 publications

(15 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The site of injury appears to be neuronal. ROS produced during ischemia-reperfusion are likely to affect especially the NMDA receptors that are sensitive to ROS both in vivo (17,27) and in vitro (1). In contrast, kainic acid elicits a similar but ischemiaresistant neuronal-vascular sequence (8).…”

Section: Discussionmentioning

confidence: 99%

N-methyl-d-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets

Domoki

Perciaccante

Shimizu

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

. N-methyl-D-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets. Am J Physiol Heart Circ Physiol 282: H1404-H1409, 2002. First published November 23, 2001 10.1152/ajpheart. 00523.2001.-N-methyl-D-aspartate (NMDA) elicits pial arteriolar dilation that has been associated with neuronal nitric oxide (NO) production. However, endothelial factors or glial P-450 epoxygenase products may play a role. We tested whether NMDA-induced pial vasodilation 1) primarily involves NO diffusion from the parenchyma to the surface arterioles, 2) involves intact endothelial function, and 3) involves a miconazole-sensitive component. Arteriolar diameters were determined using closed cranial window-intravital microscopy in anesthetized piglets. NMDA (10-100 M) elicited virtually identical dose-dependent dilations in paired arterioles (r ϭ 0.94, n ϭ 15). However, NMDA-but not bradykinin (BK)-induced dilations of arteriolar sections over large veins were reduced by 31 Ϯ 1% (means Ϯ SE, P Ͻ 0.05, n ϭ 4) compared with adjacent sections on the cortical surface. Also, 100 M NMDA increased cerebrospinal fluid levels of NO metabolites from 3.7 Ϯ 1.0 to 5.3 Ϯ 1.2 M (P Ͻ 0.05, n ϭ 6). Endothelial stunning by intracarotid injection of phorbol 12,13-dibutyrate did not affect NMDA-induced vasodilation but attenuated vascular responses to hypercapnia and BK by ϳ70% (n ϭ 7). Finally, miconazole (n ϭ 6, 20 M) pretreatment and coapplication with NMDA did not alter vascular responses to NMDA. In conclusion, NMDA appears to dilate pial arterioles exclusively through release and diffusion of NO from neurons to the pial surface in piglets. cerebral circulation; miconazole; pial arterioles; bradykinin PREVIOUS STUDIES suggest that stimulation of N-methyl-D-aspartate (NMDA) receptors on cortical neurons results in dose-dependent pial arteriolar dilation via a mechanism involving neuronal nitric oxide (NO) synthase (nNOS) activation and subsequent NO release in newborn pigs (11,29). Because cerebral resistance vessels and cortical astroglia lack NMDA receptors, cerebral vasodilation to NMDA must be initiated by substances released from activated neurons (30,38). Similar involvement of NO in NMDA-induced pial arteriolar vasodilation or increased cerebral blood flow (CBF) have been observed in many other species (14,32,40). Glutamate receptor activation either by nervous or pharmacological stimulation results in increased blood flow in a variety of regions, such as the cerebral cortex (25, 33, 41), striatum (10), hippocampus (18), cerebellum (3), and medulla (16) in rats. In all these regions, NO seems to be involved in the mechanism of CBF increase, and the major glutamate receptor subtype appears to be the NMDA receptor, except in the cerebellum (3, 40). However, many of the details of this relationship between activation of NMDA receptors and cerebrovascular dilation are unclear. Whereas there is agreement that NO is essential for NMDAinduced arteriolar dilation, it is unclear whether parenchymal-derived N...

show abstract

Section: Discussionmentioning

confidence: 99%

N-methyl-d-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets

Domoki

Perciaccante

Shimizu

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…This is an important insight for clinical use because, of course, treatments would usually only be commenced after resuscitation of an asphyxiated newborn baby. Studies in newborn piglets exposed to hypoxia demonstrate that allopurinol pretreatment successfully inhibits xanthine oxidase, increases cerebral levels of adenosine and also prevents asphyxia-induced NMDA receptor modification, thereby attenuating excitotoxicity [52,53]. The finding that allopurinol enhances brain adenosine is interesting given that adenosine is a neuromodulator in its own right, decreasing glutamate excitotoxicity but also potentially decreasing normal oligodendrocytes maturational processes [54].…”

Section: Allopurinolmentioning

confidence: 99%

Antioxidant Therapies: A Potential Role in Perinatal Medicine

2012

View full text Add to dashboard Cite

Pregnancies complicated by impaired placentation, acute severe reductions in oxygen supply to the fetus, or intrauterine infection are associated with oxidative stress to the mother and developing baby. Such oxidative stress is characterized as an upregulation in the production of oxidative or nitrative free radicals and a concomitant decrease in the availability of antioxidant species, thereby creating a state of fetoplacental oxidative imbalance. Recently, there has been a good deal of interest in the potential for the use of antioxidant therapies in the perinatal period to protect the fetus, particularly the developing brain, against oxidative stress in complications of pregnancy and birth. This review will examine why the immature brain is particularly susceptible to oxidative imbalance and will provide discussion on antioxidant treatments currently receiving attention in the adult and perinatal literature – allopurinol, melatonin, α-lipoic acid, and vitamins C and E. In addition, we aim to address the interaction between oxidative stress and the fetal inflammatory response, an interaction that may be vital when proposing antioxidant or other neuroprotective strategies.

show abstract

“…This similarity may have been due to the exposure to a single episode of asphyxia, or an episode that was not severe enough to reduce maximum receptor binding or receptor density. Studies in which recurrent episodes of asphyxia were experienced resulted in a reduction in the Bmax [36]. The lack of appreciable differences in the outcome measures in the two study groups may have been due to the mild degree of asphyxia as opposed to a severe insult, experienced by both groups.…”

Section: Discussionmentioning

confidence: 89%

Effect of Resuscitation with 21% Oxygen and 100% Oxygen on NMDA Receptor Binding Characteristics Following Asphyxia in Newborn Piglets

et al. 2007

Self Cite

View full text Add to dashboard Cite

The present study investigated the effect of reventilation with 21% and 100% oxygen following asphyxia in newborn piglets on NMDA receptor binding characteristics, Na(+), K(+)-ATPase activity, and lipid peroxidation. After achieving a heart rate less than 60 beats per minute, asphyxiated piglets were reventilated with 21% oxygen or 100% oxygen. (3)[H]MK-801 binding showed the Bmax in the 21% and 100% groups to be 1.53 +/- 0.43 and 1.42 +/- 0.35 pmol/mg protein (p = ns). Values for Kd were 4.56 +/- 1.29 and 4.17 +/- 1.05 nM (p = ns). Na(+), K(+)-ATPase activity in the 21% and 100% groups were 23.5 +/- 0.9 and 24.4 +/- 3.9 micromol Pi/mg protein/h (p = ns). Conjugated dienes (0.05 +/- 0.02 vs. 0.07 +/- 0.03 micromol/g brain) and fluorescent compounds (0.54 +/- 0.05 vs. 0.78 +/- 0.19 microg quinine sulfate/g brain), were similar in both groups (p = ns). Though lipid peroxidation products trended higher in the 100% group, these data show that NMDA receptor binding and Na(+), K(+)-ATPase activity were similar following reventilation with 21% or 100% oxygen after a single episode of mild asphyxia.

show abstract

Effect of allopurinol on NMDA receptor modification following recurrent asphyxia in newborn piglets

Cited by 24 publications

References 40 publications

N-methyl-d-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets

N-methyl-d-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets

Antioxidant Therapies: A Potential Role in Perinatal Medicine

Effect of Resuscitation with 21% Oxygen and 100% Oxygen on NMDA Receptor Binding Characteristics Following Asphyxia in Newborn Piglets

Contact Info

Product

Resources

About