Blockage of cytosolic phospholipase A2 alpha by monoclonal antibody attenuates focal ischemic brain damage in mice

Liu, Hui; Zuo, Fengtong; Wu, Huijun

doi:10.5582/bst.2017.01046

Cited by 15 publications

(11 citation statements)

References 39 publications

(52 reference statements)

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“…Nowadays, a number of studies reported that curcumin improves outcomes and attenuates focal cerebral ischemic injury in MCAO rat models (Liu et al, 2016;Miao et al, 2016;Zhao et al, 2010). Similarly, our results showed that curcumin decreased the infarct volume and improved the neurological outcomes in another different MCAO mouse model, which is more and more widely used to investigate the complicated molecular mechanisms of cerebral ischemia in recent years (Evans et al, 2017;H. Liu, Zuo, & Wu, 2017;Xia et al, 2017).…”

Section: Discussionsupporting

confidence: 77%

Curcumin protects neural cells against ischemic injury in N2a cells and mouse brain with ischemic stroke

Xie

Cai

et al. 2018

Brain and Behavior

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Background and PurposeCurcumin, a natural antioxidant isolated from Curcuma longa, has been reported to exert neuroprotective effect in animal models of ischemic stroke. However, the underlying mechanism is still not fully understood. The purpose of this study was to investigate the effect of curcumin treatment on neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion (I/R) injury and in mouse N2a cells after oxygen‐glucose deprivation/reoxygenation (OGD/R) injury and its underlying mechanism.MethodsThe cerebral I/R injury was established by 1‐hr middle cerebral artery occlusion (MCAO) and reperfusion in mice. Infarct volume was determined by TTC staining, and neurological score was evaluated by mNSS. Cell morphology in the ischemic boundary zone were detected by HE staining. The number and apoptotic rate of neurons in ischemic boundary zone were assayed by immunohistochemistry and TUNEL, respectively. Mouse neuroblastoma N2a cells were subjected to OGD/R. Cell viability was assessed with CCK‐8. The mitochondrial membrane potential was measured using JC‐1 staining. The expression of Bax, Bcl‐2, and caspase‐3 was detected using Western blotting. Besides, cellular distribution of Bax was determined by immunofluorescence assays.ResultsCurcumin treatment reduced infarct volume, improved neurological function, alleviated the morphological damage of neurons, and increased neuronal survival rate after I/R injury in vivo. Moreover, curcumin treatment improved cell viability, reduced cell apoptosis, increased Bcl‐2 protein levels while decreased Bax and caspase‐3 expressions in mouse N2a cells after OGD/R injury. Besides, curcumin treatment inhibited Bax activation and maintained mitochondrial membrane integrity.ConclusionCurcumin promotes neuron survival in vivo and in vitro to exert neuroprotective effects against ischemia injury. Moreover, our results for the first time demonstrated curcumin inhibited ischemia‐induced mitochondrial apoptosis via restricting Bax activation, which may be one of the possible mechanisms underlying the neuroprotective effects of curcumin.

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Section: Discussionsupporting

confidence: 77%

Curcumin protects neural cells against ischemic injury in N2a cells and mouse brain with ischemic stroke

Xie

Cai

et al. 2018

Brain and Behavior

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“…Brain phospholipids are highly enriched with longchain polyunsaturated fatty acids. Amongst all 84 differentially expressed lipids, almost all of them are long-chain polyunsaturated fatty acid chains (Table 1) Based on the understanding that knockout and inhibition of cPLA2 conferred neuroprotection against ischemic injury (25,26), it is a plausible hypothesis that the Lands' cycle is involved in cerebral ischemia-induced brain injury. Overstimulation of cPLA2 leads to the breakdown of membrane PC and subsequent accumulation of LPC in the damaged tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the deletion of cPLA2, the enzyme for converting PC to LPC, is neuroprotective against cerebral ischemia (24,25). Inhibition of cPLA2 alpha by a monoclonal antibody attenuated focal cerebral ischemic in mice (26). However, the specific functions of PC and LPC in ischemic brains reported in the literature are conflicting with either protective or detrimental effects.…”

Section: Introductionmentioning

confidence: 99%

An imbalanced ratio between PC(16:0/16:0) and LPC(16:0) revealed by lipidomics supports the role of the Lands cycle in ischemic brain injury

Zheng

Xie

Zheng

et al. 2021

Journal of Biological Chemistry

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Promoting brain recovery after stroke is challenging as a plethora of inhibitory molecules are produced in the brain preventing it from full healing. Moreover, the full scope of inhibitory molecules produced is not well understood. Here, using a high-sensitivity UPLC-MS-based shotgun lipidomics strategy, we semiquantitively measured the differential lipid contents in the mouse cerebral cortex recovering from a transient middle cerebral artery occlusion (MCAO). The lipidomic data were interrogated using the soft independent modeling of class analogy (SIMCA) method involving principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Statistics of the 578 confirmed lipids revealed 84 species were differentially changed during MCAO/reperfusion. The most dynamic changes in lipids occurred between 1 and 7 days post-MCAO, whereas concentrations had subsided to the Sham group level at 14 and 28 days post-MCAO. Quantitative analyses revealed a strong monotonic relationship between the reduction in phosphatidylcholine (PC)(16:0/16:0) and the increase in lysophosphatidylcholine (LPC)(16:0) levels (Spearman’s Rs = −0.86) during the 1 to 7 days reperfusion period. Inhibition of cPLA2 prevented changes in the ratio between PC(16:0/16:0) and LPC(16:0), indicating altered Land’s cycle of PC. A series of in vitro studies showed that LPC(16:0), but not PC(16:0/16:0), was detrimental to the integrity of neuronal growth cones and neuronal viability through evoking intracellular calcium influx. In contrast, PC(16:0/16:0) significantly suppressed microglial secretion of IL-1β and TNF-α, limiting neuroinflammation pathways. Together, these data support the role of the imbalanced ratio between PC(16:0/16:0) and LPC(16:0), maintained by Lands’ cycle, in neuronal damage and microglia-mediated inflammatory response during ischemic recovery.

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“…The cytosolic phospholipase A 2 alpha (cPLA 2α ), an enzyme responsible for arachidonic acid release from membrane phospholipids, plays a key role in post-ischemic brain pathology. The down-regulation of cytosolic phospholipase A 2 alpha expression [116] or blockage of its activity with specific antibodies [117] attenuates ischemic brain damage in the mouse model of cerebral ischemia-reperfusion injury. The DHA released during the ischemic event is converted enzymatically into lipid messengers.…”

Section: Lipids Of the Brain During Ischemic Strokementioning

confidence: 99%

Lipids and Lipid Mediators Associated with the Risk and Pathology of Ischemic Stroke

Kłoska

Malinowska

Gabig-Cimińska

et al. 2020

IJMS

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Stroke is a severe neurological disorder in humans that results from an interruption of the blood supply to the brain. Worldwide, stoke affects over 100 million people each year and is the second largest contributor to disability. Dyslipidemia is a modifiable risk factor for stroke that is associated with an increased risk of the disease. Traditional and non-traditional lipid measures are proposed as biomarkers for the better detection of subclinical disease. In the central nervous system, lipids and lipid mediators are essential to sustain the normal brain tissue structure and function. Pathways leading to post-stroke brain deterioration include the metabolism of polyunsaturated fatty acids. A variety of lipid mediators are generated from fatty acids and these molecules may have either neuroprotective or neurodegenerative effects on the post-stroke brain tissue; therefore, they largely contribute to the outcome and recovery from stroke. In this review, we provide an overview of serum lipids associated with the risk of ischemic stroke. We also discuss the role of lipid mediators, with particular emphasis on eicosanoids, in the pathology of ischemic stroke. Finally, we summarize the latest research on potential targets in lipid metabolic pathways for ischemic stroke treatment and on the development of new stroke risk biomarkers for use in clinical practice.

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Blockage of cytosolic phospholipase A2 alpha by monoclonal antibody attenuates focal ischemic brain damage in mice

Cited by 15 publications

References 39 publications

Curcumin protects neural cells against ischemic injury in N2a cells and mouse brain with ischemic stroke

Curcumin protects neural cells against ischemic injury in N2a cells and mouse brain with ischemic stroke

An imbalanced ratio between PC(16:0/16:0) and LPC(16:0) revealed by lipidomics supports the role of the Lands cycle in ischemic brain injury

Lipids and Lipid Mediators Associated with the Risk and Pathology of Ischemic Stroke

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