Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion.

Matsuo, Yoshiyuki; Oda, Hiroshi; Shiga, Yusei; Nakamura, Masuhisa; Ninomiya, Mitsuyoshi; Kihara, Tsuyoshi; Kogure, Kyuya

doi:10.1161/01.str.25.7.1469

Cited by 443 publications

(255 citation statements)

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“…MPO is mainly present in neutrophils, monocytes, and macrophages; thus, it has been used as a marker for infiltrated neutrophils at sites of injury. 49,50 Recently, MPO was reported to be present in brain-resident cells under pathological conditions. 18,23 The results of the present study using primary glial cell cultures strongly support the hypothesis that glial cells are among the MPO-expressing cells of the brain.…”

Section: Discussionmentioning

confidence: 99%

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Chang

Song

Jeon

et al. 2011

The American Journal of Pathology

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Rotenone exposure has emerged as an environmental risk factor for inflammation-associated neurodegenerative diseases. However, the underlying mechanisms responsible for the harmful effects of rotenone in the brain remain poorly understood. Herein, we report that myeloperoxidase (MPO) may have a potential regulatory role in rotenone-exposed brain-resident immune cells. We show that microglia, unlike neurons, do not undergo death; instead, they exhibit distinctive activated properties under rotenone-exposed conditions. Once activated by rotenone, microglia show increased production of reactive oxygen species, particularly HOCl. Notably, MPO, an HOClproducing enzyme that is undetectable under normal conditions, is significantly increased after exposure to rotenone. MPO-exposed glial cells also display characteristics of activated cells, producing proinflammatory cytokines and increasing their phagocytic activity. Interestingly, our studies with MPO inhibitors and MPO-knockout mice reveal that MPO deficiency potentiates, rather than inhibits, the rotenone-induced activated state of glia and promotes glial cell death. Furthermore, rotenone-triggered neuronal injury was more apparent in co-cultures with glial cells from Mpo ؊/؊ mice than in those from wildtype mice. Collectively, our data provide evidence that MPO has dual functionality under rotenone-exposed conditions, playing a critical regulatory role in modulating pathological and protective events in the brain.

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Section: Discussionmentioning

confidence: 99%

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Chang

Song

Jeon

et al. 2011

The American Journal of Pathology

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“…O método empregado apresenta resultados semelhantes em relação a outros que utilizam parâmetros bioquímicos, apesar destes últimos serem superiores em relação à contribuição ao conhecimento da fisiopatologia da isquemia [22][23][24][25][26][27][28] , assim como os métodos de fluxo sangüíneo cerebral que nos trazem informações da dinâmica do processo isquêmico.…”

Section: Discussionunclassified

“…Estes métodos permitem quantificar reações metabólicas que ocorrem normalmente nos tecidos, como por exemplo a atividade de diferentes enzimas [22][23][24][25][26] , a dosagem e o estudo da cinética da liberação dos neurotransmissores do tecido 27 e alterações moleculares das mitocondrias 28 . A possibilidade de estudo das alterações que ocorrem na área de penumbra é de grande interesse, pois esta é a área a ser preservada no tratamento do infarto cerebral.…”

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Avaliação da isquemia cerebral pela respiração mitocondrial: modelo experimental

Carlotti

Colli²,

Kazuo³

2001

Arq. Neuro-Psiquiatr.

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RESUMO -A isquemia cerebral acontece em várias doenças. Um dos fatores críticos para a recuperação de um paciente é a duração do processo isquêmico. A atividade cerebral depende do suprimento de energia, isto sugere que o estudo da função mitocondrial pode ser utilizado para a avaliação do dano neuronal. O objetivo deste trabalho foi o de estudar a respiração mitocondrial pela oclusão da artéria cerebral média esquerda pela técnica do fio intraluminal. Ratos da raça Wistar foram subdivididos em 4 grupos: controle e 15, 30 e 60 minutos de oclusão. Os resultados mostraram que não há diferença estatisticamente significativa entre o grupo de 15 minutos e o grupo controle. O grupo de 30 minutos teve diminuição do estado III da respiração mitocondrial comparado com o grupo controle. O grupo de 60 minutos teve diminuição dos estados III e IV comparados com o grupo controle. A respiração mitocondrial permitiu uma avaliação efetiva e precoce do processo isquêmico focal no cérebro do rato. PALAVRAS-CHAVE: respiração mitocondrial, isquemia cerebral focal. Study of brain ischemia by mitochondrial respiration: experimental modelABSTRACT -Brain ischemia occurs in several diseases. One of the critical factors for recovery of patients is the duration of the ischemic process. Brain activity depends on the energetic supply, it suggests that the study of mitochondrial function can be useful for evaluation of neuronal damage. The purpose of the present research was to study the mitochondrial respiration by occlusion of the left middle cerebral artery by intraluminal suture technique. Adults Wistar rats were subdivided in 4 groups: control, 15, 30 and 60 minutes of occlusion. Results showed that there was no significant difference between the group of 15 minutes and the control group. The group of 30 minutes had significant decrease of state III of mitochondrial respiration compared with control group. The group of 60 minutes had significant decrease in state III and IV of mitochondrial respiration compared with control group. Mitochondrial respiration allowed an early and effective evaluation of focal ischemic process of the rat brain.KEY WORDS: mitochondrial respiration, focal brain ischemia. magnésio 3 , hipotermia 4-7 , bloqueadores de canal de cálcio 8 , agentes anestésicos 9 , hemodiluição 10 , manitol 11,12 e outros 13 , porém o campo de pesquisa continua amplo. Para a avaliação da isquemia cerebral experimental vários métodos podem ser utilizados, sendo os mais importantes os métodos clínicos, morfológicos e funcionais. Os testes clínicos consistem em um exame simples e rápido, geralmente com avaliação da simetria motora, que permite classificar os animais em diversos graus de lesão 14,15 .A avaliação morfológica da isquemia cerebral é possível quando o fenômeno isquêmico foi de in- A isquemia cerebral é um problema médico ainda de difícil solução e que pode ocorrer em diferentes situações clínicas. O tratamento atual da isquemia cerebral muitas vezes não é eficaz, devido a este fato vários pesquisadores têm procurado maior...

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“…For instance, the time over which neutrophils infiltrate an ischemic stroke (beginning at 6h in experimental studies in the rat (Barone et al, 1995) and 15h in humans (Lindsberg et al, 1996) and persisting for days) mirrors edema development, suggesting that neutrophils could be causal factors (Lindsberg et al, 1996;Zhang et al, 1994, Del Zoppo et al, 2001). However studies in animal disease models have been contradictory, with some correlating neutrophils to indicators of brain edema (Del Maschio et al, 1999;Matsuo et al, 1994;Wispelwey et al, 1988;Yamasaki et al, 1995). Others show no relationship (Adelson et al, 1998;Hartl et al, 1997;Tauber et al, 1988;Whalen et al, 1999) while others suggest that neutrophils reduce BBB disruption (Ahmed et al, 2000;Lo et al, 1998;Schurer et al, 1990).…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Modulation of blood–brain barrier permeability by neutrophils: in vitro and in vivo studies

et al. 2009

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Abstract.The blood-brain barrier (BBB) restricts solute permeability across healthy cerebral endothelial cells. However, during inflammation, permeability is increased and can lead to deleterious cerebral edema. Neutrophils are early cellular participants in acute inflammation, but their effect on BBB permeability is unclear. To study this, neutrophils were applied in a resting and activated state to in vitro and in vivo models of the BBB. In vitro, human neutrophils (5 X 10 6 /ml) were activated with tumor necrosis factor (100U/ml) and leukotriene B 4 (10 -7 mol/l).Untreated neutrophils reduced permeability across the human brain endothelial cell line hCMEC/ D3. Activated neutrophils returned permeability to baseline, an effect blocked by the reactive oxygen scavengers superoxide dismutase (10U/ml) and catalase (1000U/ml). In vivo, human neutrophils (2.5 X 10 5 in 4μl) were injected into the striatum of anesthetized juvenile Wistar rats, and BBB permeability measured 30 minutes later. This was compared to control injections (4μl) of vehicle (0.9% saline) and arachidonic acid (10 -3 mol/l). The injection generated a small hematoma around the injection tract (<3μl). Untreated neutrophils induced significantly lower permeability in their vicinity than activated neutrophils, with a trend to lowered permeability compared to the vehicle control. Neither untreated nor activated neutrophils induced permeability increases, while arachidonic acid increased permeability as a positive control. This study further delineates the effect of neutrophils on the BBB, and demonstrates that resting neutrophils induce acute reductions in permeability while activated neutrophils have a neutral effect. The in vivo model reiterates some aspects of acute intracerebral hemorrhage.Section: Cellular and molecular biology of nervous systems.

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Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion.

Cited by 443 publications

References 43 publications

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Avaliação da isquemia cerebral pela respiração mitocondrial: modelo experimental

Modulation of blood–brain barrier permeability by neutrophils: in vitro and in vivo studies

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