Changes in L-arginine metabolism by Sema4D deficiency induce promotion of microglial proliferation in ischemic cortex

Sawano, Toshinori; Tsuchihashi, Ryo; Watanabe, Fumiya; Niimi, Kenta; Yamaguchi, Wataru; Yamaguchi, N; Furuyama, Tatsuo; Tanaka, Hidekazu; Matsuyama, Tomohiro; Inagaki, Shinobu

doi:10.1016/j.neuroscience.2019.03.037

Cited by 13 publications

(10 citation statements)

References 62 publications

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“…Arginine metabolism has been reported to play a key role in immunometabolic responses in microglia [331][332][333]. The current evidence suggests two alternative and competitive directions for arginine: Into the NO synthesis pathway associated with the inflammatory response or into the arginase pathway associated with wound healing and repair [334,335].…”

Section: Arginine: a Fork In The Road Aheadmentioning

confidence: 97%

Microglia: Agents of the CNS Pro-Inflammatory Response

Rodríguez‐Gómez

Kavanagh

Engskog-Vlachos

et al. 2020

Cells

227

136

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The pro-inflammatory immune response driven by microglia is a key contributor to the pathogenesis of several neurodegenerative diseases. Though the research of microglia spans over a century, the last two decades have increased our understanding exponentially. Here, we discuss the phenotypic transformation from homeostatic microglia towards reactive microglia, initiated by specific ligand binding to pattern recognition receptors including toll-like receptor-4 (TLR4) or triggering receptors expressed on myeloid cells-2 (TREM2), as well as pro-inflammatory signaling pathways triggered such as the caspase-mediated immune response. Additionally, new research disciplines such as epigenetics and immunometabolism have provided us with a more holistic view of how changes in DNA methylation, microRNAs, and the metabolome may influence the pro-inflammatory response. This review aimed to discuss our current knowledge of pro-inflammatory microglia from different angles, including recent research highlights such as the role of exosomes in spreading neuroinflammation and emerging techniques in microglia research including positron emission tomography (PET) scanning and the use of human microglia generated from induced pluripotent stem cells (iPSCs). Finally, we also discuss current thoughts on the impact of pro-inflammatory microglia in neurodegenerative diseases.

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Section: Arginine: a Fork In The Road Aheadmentioning

confidence: 97%

Microglia: Agents of the CNS Pro-Inflammatory Response

Rodríguez‐Gómez

Kavanagh

Engskog-Vlachos

et al. 2020

Cells

227

136

View full text Add to dashboard Cite

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“…During the second stage of ischemia stroke, events such as oxidant stress, blood-brain barrier breakdown and inflammatory response, cause secondary injury [5]. The investigation of post-ischemia neuroinflammation, due to its complexity, is still limited [15,28]. Arginine has been reported to exert neuroprotective effect [12].…”

Section: Discussionmentioning

confidence: 99%

“…Arginine is essential for cell survival and the deprivation of arginine leads to apoptosis [14]. Changes in L-arginine metabolism by Sema4D deficiency induce promotion of microglial proliferation in ischemic cortex [15]. The role of arginine in inflammatory response in cerebral I/R injury is not investigated.…”

Section: Introductionmentioning

confidence: 99%

Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury

et al. 2020

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Neuroinflammation is a secondary response following ischemia stroke. Arginine is a non-essential amino acid that has been shown to inhibit acute inflammatory reaction. In this study we show that arginine treatment decreases neuronal death after rat cerebral ischemia/reperfusion (I/R) injury and improves functional recovery of stroke animals. We also show that arginine suppresses inflammatory response in the ischemic brain tissue and in the cultured microglia after OGD insult. We further provide evidence that the levels of HIF-1α and LDHA are increased after rat I/R injury and that arginine treatment prevents the elevation of HIF-1α and LDHA after I/R injury. Arginine inhibits inflammatory response through suppression of HIF-1α and LDHA in the rat ischemic brain tissue and in the cultured microglia following OGD insult, and protects against ischemic neuron death after rat I/R injury by attenuating HIF-1α/LDHA-mediated inflammatory response. Together, these results indicate a possibility that arginine-induced neuroprotective effect may be through the suppression of HIF-1α/LDHA-mediated inflammatory response in microglia after cerebral ischemia injury.

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“…The nitric oxide (NO) which is produced by the ischemia activated inducible nitric oxide synthase (iNOS), affecting cell survival by changing the functions of caspases and metalloproteases ( Abdul-Muneer et al, 2013 ). Sema4D upregulates NO production by inducing IFN-β expression in microglial cells in the ischemic cortex ( Sawano et al, 2019 ; Tsuchihashi et al, 2020 ). In ameboid microglial cells, L-arginine is metabolized by iNOS to synthesize NO through Sema4D-RhoA-MAPK/ERK signal ( Figure 3B ; Bijian et al, 2005 ; Okuno et al, 2010 ; Sawano et al, 2015 ).…”

Section: Semaphorin 4dmentioning

confidence: 99%

Role of Semaphorins in Ischemic Stroke

Zhu

2022

Front. Mol. Neurosci.

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Ischemic stroke is one of the major causes of neurological morbidity and mortality in the world. Although the management of ischemic stroke has been improved significantly, it still imposes a huge burden on the health and property. The integrity of the neurovascular unit (NVU) is closely related with the prognosis of ischemic stroke. Growing evidence has shown that semaphorins, a family of axon guidance cues, play a pivotal role in multiple pathophysiological processes in NVU after ischemia, such as regulating the immune system, angiogenesis, and neuroprotection. Modulating the NVU function via semaphorin signaling has a potential to develop a novel therapeutic strategy for ischemic stroke. We, therefore, review recent progresses on the role of semphorin family members in neurons, glial cells and vasculature after ischemic stroke.

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Changes in L-arginine metabolism by Sema4D deficiency induce promotion of microglial proliferation in ischemic cortex

Cited by 13 publications

References 62 publications

Microglia: Agents of the CNS Pro-Inflammatory Response

Microglia: Agents of the CNS Pro-Inflammatory Response

Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury

Role of Semaphorins in Ischemic Stroke

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