Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke

Kim, Jennifer E.; Lee, Ryan P.; Yazigi, Eli; Atta, Lyla; Feghali, James; Pant, Ayush; Jain, Aanchal; Levitan, Idan; Kim, Eileen; Patel, Kisha; Kannapadi, Nivedha; Shah, Pavan; Bibic, Adnan; Hou, Zhipeng; Caplan, Justin M.; Gonzalez, L. Fernando; Huang, Judy; Xu, Risheng; Fan, Jean; Tyler, Betty; Brem, Henry; Boussiotis, Vassiliki A.; Jantzie, Lauren; Robinson, Shenandoah; Koehler, Raymond C.; Lim, Michael; Tamargo, Rafael J.; Jackson, Christopher M.

doi:10.1016/j.bbi.2023.12.007

Cited by 9 publications

(4 citation statements)

References 76 publications

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“…Our search identified several treatments that had a disproportionate effect on edema/swelling compared to the effect on infarct size ( Table 1 ) and thus might be considered potential candidates for reducing edema independent of infarct size. These included glibenclamide [ 20 , 21 ]; dimethyl fumarate (Tecfidera ® ) [ 22 ] and its metabolite monomethyl fumarate [ 23 ]; soluble programmed death ligand-1 [ 24 ]; and canagliflozin [ 25 ]. All of these drugs reduced edema/swelling without significantly reducing infarct size when administered post-ischemia in MCAo models.…”

Section: Resultsmentioning

confidence: 99%

“…A refinement to this approach in which there is no effect of treatment on infarct volume was presented by Kim et al [ 24 ]. These authors studied the effect of soluble programmed death ligand-1 (sPD-L1) in a mouse MCAo (0.75/48 h) model using high-resolution magnetic resonance imaging.…”

Section: Resultsmentioning

confidence: 99%

“…The study by Kim et al [ 24 ] not only illustrates the utility of normalization but also underscores the importance of studying an MCAo model with severe ischemia. As noted previously, it is well known that the mouse MCAo/R model of stroke is associated with significant variability in infarct size [ 32 ], especially with the moderate ischemic insults that are frequently utilized.…”

Section: Resultsmentioning

confidence: 99%

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Brain Swelling versus Infarct Size: A Problematizing Review

Simard,

Wilhelmy,

Tsymbalyuk

et al. 2024

Brain Sciences

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In human stroke, brain swelling is an important predictor of neurological outcome and mortality, yet treatments to reduce or prevent brain swelling are extremely limited, due in part to an inadequate understanding of mechanisms. In preclinical studies on cerebroprotection in animal models of stroke, historically, the focus has been on reducing infarct size, and in most studies, a reduction in infarct size has been associated with a corresponding reduction in brain swelling. Unfortunately, such findings on brain swelling have little translational value for treating brain swelling in patients with stroke. This is because, in humans, brain swelling usually becomes evident, either symptomatically or radiologically, days after the infarct size has stabilized, requiring that the prevention or treatment of brain swelling target mechanism(s) that are independent of a reduction in infarct size. In this problematizing review, we highlight the often-neglected concept that brain edema and brain swelling are not simply secondary, correlative phenomena of stroke but distinct pathological entities with unique molecular and cellular mechanisms that are worthy of direct targeting. We outline the advances in approaches for the study of brain swelling that are independent of a reduction in infarct size. Although straightforward, the approaches reviewed in this study have important translational relevance for identifying novel treatment targets for post-ischemic brain swelling.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Brain Swelling versus Infarct Size: A Problematizing Review

Simard,

Wilhelmy,

Tsymbalyuk

et al. 2024

Brain Sciences

View full text Add to dashboard Cite

show abstract

“…Although PLA can inhibit viral replication by inhibiting glutamine metabolism, it can also be used as a potential antiviral drug. However, for the body, immune cells that require a large number of substances and considerable energy for metabolic functions, including the activation of macrophages and the proliferation and activation of T/B lymphocytes caused by infection, also require a large intake of glucose and glutamine to meet their metabolic needs in terms of energy consumption and substance intake [ 19 , 20 , 21 ]. We have formulated the following questions to provide valuable insights for future scholars in this field: Does PLA have an inhibitory effect on the activation and proliferation of these immune cells?…”

Section: Discussionmentioning

confidence: 99%

The Accumulation of Phenyllactic Acid Impairs Host Glutamine Metabolism and Inhibits African Swine Fever Virus Replication: A Novel Target for the Development of Anti-ASFV Drugs

Dai,

Ma,

Wubshet

et al. 2024

Viruses

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African swine fever (ASF) is a highly contagious and hemorrhagic disease caused by infection with the African swine fever virus (ASFV), resulting in a mortality rate of up to 100%. Currently, there are no effective treatments and commercially available vaccines for ASF. Therefore, it is crucial to identify biochemicals derived from host cells that can impede ASFV replication, with the aim of preventing and controlling ASF. The ASFV is an acellular organism that promotes self-replication by hijacking the metabolic machinery and biochemical resources of host cells. ASFV specifically alters the utilization of glucose and glutamine, which are the primary metabolic sources in mammalian cells. This study aimed to investigate the impact of glucose and glutamine metabolic dynamics on the rate of ASFV replication. Our findings demonstrate that ASFV infection favors using glutamine as a metabolic fuel to facilitate self-replication. ASFV replication can be substantially inhibited by blocking glutamine metabolism. The metabolomics analysis of the host cell after late-stage ASFV infection revealed a significant disruption of normal glutamine metabolic pathways due to the abundant expression of PLA (phenyllactic acid). Pretreatment with PLA also inhibited ASFV proliferation and glutamine consumption following infection. The metabolomic analysis also showed that PLA pretreatment greatly slowed down the metabolism of amino acids and nucleotides that depend on glutamine. The depletion of these building blocks directly hindered the replication of ASFV by decreasing the biosynthetic precursors produced during the replication of ASFV’s progeny virus. These findings provide valuable insight into the possibility of pursuing the development of antiviral drugs against ASFV that selectively target metabolic pathways.

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Therapeutic implications for the PD-1 axis in cerebrovascular injury

Feghali,

Jackson

2024

Neurotherapeutics

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Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke

Cited by 9 publications

References 76 publications

Brain Swelling versus Infarct Size: A Problematizing Review

Brain Swelling versus Infarct Size: A Problematizing Review

The Accumulation of Phenyllactic Acid Impairs Host Glutamine Metabolism and Inhibits African Swine Fever Virus Replication: A Novel Target for the Development of Anti-ASFV Drugs

Therapeutic implications for the PD-1 axis in cerebrovascular injury

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