Neuroprotective effect of aminoguanidine on transient focal ischaemia in the rat brain

Cash, Diana; Beech, John S.; Rayne, Richard C.; Bath, Philip M.W.; Meldrum, Brian S.; Williams, Steven

doi:10.1016/s0006-8993(01)02508-2

Cited by 61 publications

(36 citation statements)

References 48 publications

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“…The fact that iNOS expression was still detected in the penumbra of infarcts older than 72 h is in agreement with studies showing that selective iNOS inhibition was neuroprotective 72 h post ischemia in the adult (23,24) and neonatal (25) rat hypoxic-ischemic model. In contrast, a decrease in NOS activity was reported by 24 h post ischemia in the rat pup (9).…”

Section: Discussionsupporting

confidence: 90%

Astrocytic-Inducible Nitric Oxide Synthase in the Ischemic Developing Human Brain

Askalan

deVeber

et al. 2006

Pediatr Res

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Variability in the expression of apoptotic and inflammatory mediators with time after an ischemic insult and their role in the expansion of cerebral infarcts are still controversial. This study examines DNA degradation and the expression of activated caspase-3 and iNOS, inducible nitric oxide (iNOS) in the human developing brain. Autopsy specimens from children with a neuropathologic diagnosis of focal ischemic infarct were included in the study. The specimens were classified based on the clinical history as acute (Ͻ24 h, n ϭ 5), subacute (24 -72 h, n ϭ 8), or old (Ͼ72 h, n ϭ 6) infarcts. Immunohistochemical staining for caspase-3, iNOS and TUNEL were then performed on all infarcts alongside age-matched controls. TUNEL staining was detected in regions of all infarcts. Expression of iNOS was significantly higher than that of caspase-3 in the penumbra of subacute infarcts (p ϭ 0.02). Glial fibrillary acidic protein and iNOS staining co-localized in the penumbra of acute and subacute infarcts. These results suggest that cell death continues to occur for more than 3 d post ischemic insult. Cell death in the penumbra of subacute infarcts is partially caspase-3 independent and may be attributed to nitric oxide. Astrocytes are a source of iNOS and may play a role in the evolution of pediatric brain injury days after the initial insult.

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Section: Discussionsupporting

confidence: 90%

Astrocytic-Inducible Nitric Oxide Synthase in the Ischemic Developing Human Brain

Askalan

deVeber

et al. 2006

Pediatr Res

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“…4 However, inducible NOS inhibition after reperfusion in a rat MCAO model 39,40 showed a 30% to 40% reduction in infarct volume from 72 hours after MCAO. Furthermore, it was shown in a 7-day-old rat hypoxia-ischemia model that combined preand post-hypoxia-ischemia inducible NOS inhibition reduced infarct volumes by approximately 90%.…”

Section: Discussionmentioning

confidence: 98%

Neuroprotection by Selective Nitric Oxide Synthase Inhibition at 24 Hours After Perinatal Hypoxia-Ischemia

Peeters-Scholte

Koster

Veldhuis

et al. 2002

Stroke

105

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Background and Purpose-Perinatal hypoxia-ischemia is a major cause of neonatal morbidity and mortality. Until now no established neuroprotective intervention after perinatal hypoxia-ischemia has been available. The delay in cell death after perinatal hypoxia-ischemia creates possibilities for therapeutic intervention after the initial insult. Excessive nitric oxide and reactive oxygen species generated on hypoxia-ischemia and reperfusion play a key role in the neurotoxic cascade. The present study examines the neuroprotective properties of neuronal and inducible but not endothelial nitric oxide synthase inhibition by 2-iminobiotin in a piglet model of perinatal hypoxia-ischemia. Methods-Twenty-three newborn piglets were subjected to 60 minutes of hypoxia-ischemia, followed by 24 hours of reperfusion and reoxygenation. Five additional piglets served as sham-operated controls. On reperfusion, piglets were randomly treated with either vehicle (nϭ12) or 2-iminobiotin (nϭ11). At 24 hours after hypoxia-ischemia, the cerebral energy state, presence of vasogenic edema, amount of apparently normal neuronal cells, caspase-3 activity, amount of terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL)-positive cells, and degree of tyrosine nitration were assessed. Results-A 90% improvement in cerebral energy state, 90% reduction in vasogenic edema, and 60% to 80% reduction in apoptosis-related neuronal cell death were demonstrated in 2-iminobiotin-treated piglets at 24 hours after hypoxiaischemia. A significant reduction in tyrosine nitration in the cerebral cortex was observed in 2-iminobiotin-treated piglets, indicating decreased formation of reactive nitrogen species. Conclusions-Simultaneous and selective inhibition of neuronal and inducible nitric oxide synthase by 2-iminobiotin is a promising strategy for neuroprotection after perinatal hypoxia-ischemia.

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“…9,10 In addition, in a recent clinical trial, infliximab-which is used to manage diseases such as rheumatoid arthritis and Crohn's disease and dermatologic, chronic ocular and neurological diseases-was indicated as an alternative conservative therapy. [11][12][13] However, no study has investigated the effects of infliximab on I/R damage in rat kidneys. Therefore, this study was undertaken to examine whether infliximab shows a protective effect in experimental rat models with I/Rinduced renal damage.…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Infliximab on Ischemia/Reperfusion-Induced Damage in Rat Kidney

et al. 2012

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Objective: To investigate the protective effect of infliximab on ischemia-reperfusion (I/R) injury of the rat kidney. Methods: Twenty-eight male Wistar albino rats were divided into four groups: sham-operated, I/R, I/R with infliximab administered before ischemia [I/R þ infliximab (bi)], and I/R with infliximab administered before reperfusion [I/R þ infliximab (br)]. After a right nephrectomy to produce damage, the left renal vessels were occluded for 60 min, followed by 24-h reperfusion in rats. Changes in the rat kidney were observed by measuring the tissue levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), and superoxide dismutase (SOD) and by evaluating hematoxylin-eosin (H&E)-stained and periodic acid-Schiff (PAS) sections. Results: The MDA and MPO levels in the I/R group were significantly higher than in the other groups (p < 0.05), and the SOD and GSH levels in the I/R þ infliximab (bi) and I/R þ infliximab (br) groups were significantly higher than in the I/R group (p < 0.05). However, histological examination revealed that the I/R þ infliximab (bi) group and the I/R þ infliximab (br) group had significantly fewer tubular changes and interstitial inflammatory cell infiltration than the I/R group. Conclusion: These results show that infliximab may protect against I/R injury in the rat I/R model.

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Neuroprotective effect of aminoguanidine on transient focal ischaemia in the rat brain

Cited by 61 publications

References 48 publications

Astrocytic-Inducible Nitric Oxide Synthase in the Ischemic Developing Human Brain

Astrocytic-Inducible Nitric Oxide Synthase in the Ischemic Developing Human Brain

Neuroprotection by Selective Nitric Oxide Synthase Inhibition at 24 Hours After Perinatal Hypoxia-Ischemia

Protective Effect of Infliximab on Ischemia/Reperfusion-Induced Damage in Rat Kidney

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