IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8<sup>+</sup> T cells

Zhou, Yue; Wang, Xin; Tang, Dan; Li, Yan; Jiao, Yingfu; Gan, Yu; Hu, Xiaoming; Yang, Liqun; Yu, Weifeng; Stetler, R. Anne; Li, Peiying; Wen, Daxiang

doi:10.1111/cns.13084

Cited by 36 publications

(44 citation statements)

References 42 publications

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“…Our data indicate that 3 µg/kg VT treatment in T1DM stroke rats significantly increases axon density (BS, p < 0.001, Figure 1C), myelin density (LFB, p < 0.01, Figure 1D), and number of oligodendrocyte progenitor cells (NG2, p < 0.01, Figure 2A) in the IBZ compared to PBS‐treated T1DM stroke rats. MBP is a marker for the integrity of myelin sheath, SMI‐32 is a marker for demyelinated axons, and an increase in the ratio of SMI‐32 to MBP is an established indicator of white matter injury 32–36 . Our data also indicate that 3 µg/kg VT treatment in T1DM stroke rats significantly increases MBP( p < 0.001, Figure 2B), decreases SMI‐32 ( p < 0.01, Figure 2C), and decreases SMI‐32/MBP ratio ( p < 0.01, Figure 2D) in the IBZ compared to PBS‐treated T1DM stroke rats.…”

Section: Resultssupporting

confidence: 55%

“…Ischemic stroke is an established cause of white matter injury 35,36,52 . Increased white matter injury is associated with poor long‐term functional outcomes after stroke in experimental models of DM, 31,39 as well as after traumatic brain injury 33,53 .…”

Section: Discussionmentioning

confidence: 99%

“…Diabetes reduces the proliferation and survival of oligodendrocyte progenitor cells and impairs the generation of oligodendrocytes in white matter lesions after stroke 31,54 . Therapeutics, that promote the differentiation and maturation of oligodendrocyte progenitor cells and attenuate microglia/macrophage activation and neuroinflammation, improve long‐term neurological outcome following stroke, 35 as well as hypoxia‐ischemia injury 34 . Ang1 promotes angiogenesis which can ultimately improve white matter integrity through increased blood flow and oxygen supply to ischemic tissue 55 .…”

Section: Discussionmentioning

confidence: 99%

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Treatment with an Angiopoietin‐1 mimetic peptide promotes neurological recovery after stroke in diabetic rats

et al. 2020

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Aim Vasculotide (VT), an angiopoietin‐1 mimetic peptide, exerts neuroprotective effects in type one diabetic (T1DM) rats subjected to ischemic stroke. In this study, we investigated whether delayed VT treatment improves long‐term neurological outcome after stroke in T1DM rats. Methods Male Wistar rats were induced with T1DM, subjected to middle cerebral artery occlusion (MCAo) model of stroke, and treated with PBS (control), 2 µg/kg VT, 3 µg/kg VT, or 5.5 µg/kg VT. VT treatment was initiated at 24 h after stroke and administered daily (i.p) for 14 days. We evaluated neurological function, lesion volume, vascular and white matter remodeling, and inflammation in the ischemic brain. In vitro, we evaluated the effects of VT on endothelial cell capillary tube formation and inflammatory responses of primary cortical neurons (PCN) and macrophages. Results Treatment of T1DM‐stroke with 3 µg/kg VT but not 2 µg/kg or 5.5 µg/kg significantly improves neurological function and decreases infarct volume and cell death compared to control T1DM‐stroke rats. Thus, 3 µg/kg VT dose was employed in all subsequent in vivo analysis. VT treatment significantly increases axon and myelin density, decreases demyelination, decreases white matter injury, increases number of oligodendrocytes, and increases vascular density in the ischemic border zone of T1DM stroke rats. VT treatment significantly decreases MMP9 expression and decreases the number of M1 macrophages in the ischemic brain of T1DM‐stroke rats. In vitro, VT treatment significantly decreases endothelial cell death and decreases MCP‐1, endothelin‐1, and VEGF expression under high glucose (HG) and ischemic conditions and significantly increases capillary tube formation under HG conditions when compared to non‐treated control group. VT treatment significantly decreases inflammatory factor expression such as MMP9 and MCP‐1 in macrophages subjected to LPS activation and significantly decreases IL‐1β and MMP9 expression in PCN subjected to ischemia under HG conditions. Conclusion Delayed VT treatment (24 h after stroke) significantly improves neurological function, promotes vascular and white matter remodeling, and decreases inflammation in the ischemic brain after stroke in T1DM rats.

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Section: Resultssupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Treatment with an Angiopoietin‐1 mimetic peptide promotes neurological recovery after stroke in diabetic rats

et al. 2020

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“…IL‐17A (a member of IL‐17 cytokines) activation contributes to BBB disruption by inducing oxidative stress, which then activates the endothelium and downregulates TJ protein occludin 137 . In addition, peripheral CD8 + T cells activation and brain infiltration are detrimental to neural tissue after stroke, in which IL‐2 plays a role 138 . CD4 + and CD8 + T cells are found in the brain up to one month post ischemic stroke, and their prolonged activation may affect the outcome of stroke 139 .…”

Section: Mechanisms Of Peripheral Inflammation‐induced Bbb Disruptionmentioning

confidence: 99%

Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms

2020

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The blood–brain barrier (BBB) is an important physiological barrier that separates the central nervous system (CNS) from the peripheral circulation, which contains inflammatory mediators and immune cells. The BBB regulates cellular and molecular exchange between the blood vessels and brain parenchyma. Normal functioning of the BBB is crucial for the homeostasis and proper function of the brain. It has been demonstrated that peripheral inflammation can disrupt the BBB by various pathways, resulting in different CNS diseases. Recently, clinical research also showed CNS complications following SARS‐CoV‐2 infection and chimeric antigen receptor (CAR)‐T cell therapy, which both lead to a cytokine storm in the circulation. Therefore, elucidation of the mechanisms underlying the BBB disruption induced by peripheral inflammation will provide an important basis for protecting the CNS in the context of exacerbated peripheral inflammatory diseases. In the present review, we first summarize the physiological properties of the BBB that makes the CNS an immune‐privileged organ. We then discuss the relevance of peripheral inflammation‐induced BBB disruption to various CNS diseases. Finally, we elaborate various factors and mechanisms of peripheral inflammation that disrupt the BBB.

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“…For each inability to carry out the test, one point was scored. The scale was graded from 0 (normal function) to 18 (maximum inability) [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Isofuranodiene, a Natural Sesquiterpene Isolated from Wild Celery (Smyrnium olusatrum L.), Protects Rats against Acute Ischemic Stroke

et al. 2021

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The myrrh-like furanosesquiterpene isofuranodiene (IFD) is the main constituent of wild celery (Smyrnium olusatrum L., Apiaceae), an overlooked vegetable that was cultivated during the Roman Empire. In the present study, we investigated the protective effects of IFD pre-treatment against oxidative stress and inflammatory response in an animal model of ischemic stroke. IFD was isolated by the crystallization of Smyrnium olusatrum essential oil, and its structure and purity were confirmed by NMR and HPLC analyses. Acute pre-treatment of IFD (10 mg/kg i.p.) significantly reduced the levels of the inflammatory cytokines IL-1β and TNF-α, the expression of pNF-κB/NF-κB, and the lipid peroxidation indicator MDA. Finally, IFD boosted a faster recovery and better scores in grid-walking and modified neurological severity scores (mNSS) tests. Taken together, these findings indicate IFD as a promising lead compound for the discovery of new treatments of brain ischemia.

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IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8⁺ T cells

Cited by 36 publications

References 42 publications

Treatment with an Angiopoietin‐1 mimetic peptide promotes neurological recovery after stroke in diabetic rats

Treatment with an Angiopoietin‐1 mimetic peptide promotes neurological recovery after stroke in diabetic rats

Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms

Isofuranodiene, a Natural Sesquiterpene Isolated from Wild Celery (Smyrnium olusatrum L.), Protects Rats against Acute Ischemic Stroke

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IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells

Cited by 36 publications

References 42 publications

Treatment with an Angiopoietin‐1 mimetic peptide promotes neurological recovery after stroke in diabetic rats

Treatment with an Angiopoietin‐1 mimetic peptide promotes neurological recovery after stroke in diabetic rats

Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms

Isofuranodiene, a Natural Sesquiterpene Isolated from Wild Celery (Smyrnium olusatrum L.), Protects Rats against Acute Ischemic Stroke

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IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8⁺ T cells