Changes in major phospholipids of mitochondria during postischemic reperfusion in rat brain

Nakahara, Ichirō; Kikuchi, Hiroe; Taki, Waro; Nishi, Syogo; Kito, Makoto; Yonekawa, Yasuhiro; Goto, Yasunobu; Ogata, Nobuyoshi

doi:10.3171/jns.1992.76.2.0244

Cited by 71 publications

(37 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Following arterial occlusion in brain, production of reactive oxygen species (ROS) is increased in ischemic areas during early reperfusion (Chan 1996;Piantadosi and Zhang 1996;Kuroda and Siesjo 1997). Exposure to elevated ROS levels results in oxidation of mitochondrial lipids, sulfhydryl groups and iron sulfur complexes of mitochondrial respiratory enzymes (Wagner et al 1990;Gilboe et al 1991;Nakahara et al 1992;Liu et al 1993) leading to impairment of mitochondrial oxidative phosphorylation. Different isoforms of nitric oxide synthase are activated during cerebral ischemia (Endoh et al 1994;Nakashima et al 1995;Bolanos et al 1997;Wiencken and Casagrande 1999) leading to excessive production of nitric oxide (NO).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of mitochondrial function in astrocytes: implications for neuroprotection

Voloboueva¹,

Suh²,

Swanson³

et al. 2007

J Neurochem

View full text Add to dashboard Cite

Much evidence suggests that astrocytes protect neurons against ischemic injury. Although astrocytes are more resistant to some insults than neurons, few studies offer insight into the real time changes of astrocytic protective functions with stress. Mitochondria are one of the primary targets of ischemic injury in astrocytes. We investigated the time course of changes in astrocytic ATP levels, plasma membrane potential, and glutamate uptake, a key protective function, induced by mitochondrial inhibition. Our results show that significant functional change precedes reduction in astrocytic viability with mitochondrial inhibition. Using the mitochondrial inhibitor fluorocitrate (FC, 0.25 mM) that is preferentially taken by astrocytes we found that inhibition of astrocyte mitochondria increased vulnerability of co-cultured neurons to glutamate toxicity. In our studies the rates of FC-induced astrocytic mitochondrial depolarization were accelerated in mixed astrocyte/neuron cultures. We hypothesized that the more rapid mitochondrial depolarization was promoted by an additional energetic demand imposed be the co-cultured neurons. To test this hypothesis we exposed pure astrocytic cultures to 0.01 -1 mM aspartate as a metabolic load. Aspartate application accelerated the rates of FC-induced mitochondrial depolarization, and, at 1 mM, induced astrocytic death, suggesting that strong energetic demands during ischemia can compromise astrocytic function and viability.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of mitochondrial function in astrocytes: implications for neuroprotection

Voloboueva¹,

Suh²,

Swanson³

et al. 2007

J Neurochem

View full text Add to dashboard Cite

show abstract

“…Activation of PLA 2 is harmful to neurons in several ways: 1) membrane phospholipid degradation, 2) increased Ca 2+ influx, 3) formation of lyso-PC that inhibits CCT (50), 4) ArAc release and metabolism by cyclooxygenases/ lipoxygenases (COX/LOX) ( Figure 1). Mitochondrial PLA 2 is a sPLA 2 that acts on PC, PE, and cardiolipin (51,52). Induction of PLA 2 has been shown to result in damage to the mitochondrial respiratory chain (53).…”

Section: Pc Hydrolysis By Phospholipasesmentioning

confidence: 99%

Integration of cytokine biology and lipid metabolism in stroke

Adibhatla

Dempsy²,

Hatcher³

2008

Front Biosci

View full text Add to dashboard Cite

Cytokines regulate the innate and adaptive immune responses and are pleiotropic, redundant and multifunctional. Expression of most cytokines, including TNF-α and IL-1α/ß, is very low in normal brain. Metabolism of lipids is of particular interest due to their high concentration in the brain. Inflammatory response after stroke suggests that cytokines (TNF-α, IL-1 α/ß, IL-6), affect the phospholipid metabolism and subsequent production of eicosanoids, ceramide, and ROS that may potentiate brain injury. Phosphatidylcholine and sphingomyelin are source for lipid messengers. Sphingomyelin synthase serves as a bridge between metabolism of glycerolipids and sphingolipids. TNF-α and IL-1 α/ß can induce phospholipases (A 2 , C, and D) and sphingomyelinases, and concomitantly proteolyse phosphatidylcholine and sphingomyelin synthesizing enzymes. Together, these alterations contribute to loss of phosphatidylcholine and sphingomyelin after stroke that can be attenuated by inhibiting TNF-α or IL-1 α/ß signaling. Inflammatory responses are instrumental in the formation and destabilization of atherosclerotic plaques. Secretory PLA 2 IIA is found in human atherosclerotic lesions and is implicated in initiation, progression and maturation of atherosclerosis, a risk factor for stroke. Lipoprotein-PLA 2 , part of apolipoprotein B-100 of LDL, plays a role in vascular inflammation and coronary endothelial dysfunction. Cytokine antagonism attenuated secretory PLA 2 IIA actions, suggesting cytokine-lipid integration studies will lead to new concepts contributing to bench-to-bedside transition for stroke therapy.

show abstract

“…Este processo é denominado de "lesão de reperfusão" 6, 18,19 . Os estudos em modelos experimentais de isquemia global completa ou incompleta seguido de reperfusão em ratos, mostraram que a reperfusão de curta duração (< 30') propicia a recuperação total ou parcial do consumo de O 2 17,19 , e que a reperfusão prolongada reduz novamente o consumo de O 2 17, [20][21][22][23] . Não encontramos na literatura estudos experimentais com isquemia cerebral focal seguida de reperfusão de curta duração.…”

Section: Discussionunclassified

“…Isquemias transitórias com períodos de reperfusão em ratos parecem inicialmente menos danosos ao tecido cerebral quando comparadas à isquemia continua com tempo semelhante a soma dos períodos de isquemia intermitente, 16,26 porém tardiamente a performance dos animais foi semelhante 16 . De uma maneira geral, a reperfusão parece não interferir com a função mitocondrial em tecidos cerebrais submetidos até 30 minutos de isquemia, porém períodos mais longos de isquemia fazem com que a retomada da função mitocondrial não seja completa com os níveis de consumo de O 2 , mantendo-se abaixo do período pré-isquêmico 6,17,20,21,25 . Em nosso estudo a reperfusão foi efetuada durante 10 minutos, após os períodos variáveis de isquemia.…”

Section: Discussionunclassified

Análise da respiração mitocondrial em tecido cerebral de gato após isquemia e reperfusão

2002

View full text Add to dashboard Cite

RESUMOIntrodução -A isquemia cerebral é uma doença freqüente e de difícil tratamento médico. De particular interesse neurocirúrgico são as situações de vasoespasmo após hemorragia subaracnóidea, de oclusão temporária de vasos nas neurocirurgias e de tromboses de artérias intracranianas. A lesão cerebral resultante da isquemia depende da sua duração e pode ser agravada pela reperfusão do território isquêmico. Vários estudos clínicos e experimentais têm sido realizados para melhor entender esses fenômenos. Objetivo -Este trabalho visou a avaliação precoce dos efeitos da isquemia focal seguida da reperfusão no cérebro de gatos. Métodos -A isquemia cerebral foi provocada por clipagem temporária da artéria cerebral média por tempos determinados com reperfusão durante 10 minutos, e avaliação foi efetuada através da análise da respiração mitocondrial no tecido isquemiado. Resultados -Houve redução significativa no consumo de O2 nas amostras de tecido cerebral isquemiado por 60 minutos, seguidos de 10 minutos de reperfusão, quando comparadas ao tecido cerebral contralateral (não isquemiado). Conclusões -Com base nos resultados obtidos, pode-se concluir que o tempo de duração da isquemia foi um fator determinante na alteração da respiração mitocondrial de gatos submetidos à isquemia e reperfusão de curta duração (alterações significativas apenas após 60 minutos de isquemia seguidos de 10 de reperfusão). Disponível em URL: http://www.scielo.br/acb Descritores -isquemia, reperfusão, respiração mitocondrial. ABSTRACTObjective -Brain ischemia is considered a disease difficult to be treated. Despite many other clinical situations, of particular interest for neurosurgery is its occurrence in cerebral vasoespam following subarachnoid hemorrhage, in temporary occlusion of intracranial vessels during neurosurgeries and, in intracranial arterial thrombosis. The cerebral lesion caused by isquemia is time-related and it can aggravated by the reperfusion of the ischemic site. Many clinical and experimental studies have been perfomed aiming the better understanding of these phenomena. This study aimed to analyse the precocious effects of focal isquemia and reperfusion uppon the brain of cats. Methods -Focal brain ischemia was performed by temporary clipping of the middle cerebral artery for determined times followed by reperfusion during 10

show abstract

Changes in major phospholipids of mitochondria during postischemic reperfusion in rat brain

Cited by 71 publications

References 39 publications

Inhibition of mitochondrial function in astrocytes: implications for neuroprotection

Inhibition of mitochondrial function in astrocytes: implications for neuroprotection

Integration of cytokine biology and lipid metabolism in stroke

Análise da respiração mitocondrial em tecido cerebral de gato após isquemia e reperfusão

Contact Info

Product

Resources

About