Microglia-derived interleukin-10 accelerates post-intracerebral hemorrhage hematoma clearance by regulating CD36

Li, Qian; Lan, Xi; Han, Xiaoning; Durham, Frederick; Wan, Jieru; Weiland, Abigail; Koehler, Raymond C.; Wang, Jian

doi:10.1016/j.bbi.2021.02.001

“…Cell-based therapies using M2-like macrophages could be protective therapeutic strategies against stroke [49]. Li et al [50] showed that IL-10 could regulate microglial phagocytosis and macrophage infiltration after intracerebral hemorrhage by regulating CD36. Adipocyte fatty acid-binding protein plays a role in the stroke prognosis [51].…”

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confidence: 99%

The Prognostic Determinant of Interleukin-10 in Patients with Acute Ischemic Stroke: An Analysis from the Perspective of Disease Management

Sun

¹

,

Wang

²

,

Nan

³

2021

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Background. In patients with ischemic stroke, the role of anti-inflammatory cytokine Interleukin-10 (IL-10) in predicting risk and outcomes is not very clear. This study is aimed at prospectively assessing the prognostic determinant value of IL-10 in patients with acute ischemic stroke in a cohort of Chinese people. Methods. In a prospective cohort study, consecutive first-ever patients with acute ischemic stroke admitted to our hospital were included from October 2019 to October 2020. The serum level of IL-10 was measured at baseline. A structured follow-up telephone interview was performed on day 90 after admission. Logistic regression analyses were used to assess the prognostic value of IL-10 to predict the poor functional outcome (defined as a modified Rankin Scale score of 3 to 6) and mortality. Results. The median age of the 236 enrolled patients was 65 years (interquartile range (IQR), 56-76), and 57.6% were male. There was a negative correlation between the National Institutes of Health Stroke Scale (NIHSS) score and IL-10 serum levels ( r Spearman = − 0.221 , P = 0.001 ). Patients with elevated IL-10 levels (> the highest quartile = 5.24 pg / mL ; n = 79 ) were at significantly lower risk of poor functional outcomes (odds ratio (OR), 0.35; 95% confidence interval (CI), 0.19 to 0.63; P < 0.001 ) and mortality ( OR = 0.24 ; 95% CI = 0.11 –0.52; P < 0.001 ) compared with patients with IL-10 levels in the lowest three quartiles. Conclusions. Reduced serum levels of IL-10 were independently associated with both the clinical severity at admission and a poor functional prognosis in ischemic stroke patients, suggesting that the anti-inflammatory cytokine IL-10 was an important prognostic determinant.

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“…Nevertheless, little is known about the function of PEMFs in microglia and their effects on hematoma clearance. CD36, also known as the scavenger receptor B2, is a vital hematoma clearance receptor expressed in microglia 31 . We observed that PEMFs stimulated microglial CD36 activation in vivo and in vitro after PEMF treatment.…”

Section: Discussionmentioning

confidence: 99%

Pulsed Electromagnetic Fields Protect Against Brain Injury After Intracerebral Hemorrhage: Involvement Of Anti-Inflammatory Processes And Hematoma Clearance Via CD36

Yang

¹

,

Wang

²

,

Liu

³

et al. 2021

Preprint

0

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Background: Intracerebral hemorrhage causes high mortality and morbidity, but its therapy methods are limited. In the present study, pulsed electromagnetic fields (PEMFs) were demonstrated to have beneficial effects on an intracerebral hemorrhage (ICH) model. This study explored the effects and underlying mechanism of PEMFs in a mouse model of ICH and cultured BV2 cells.Methods: PEMFs were applied 24 hours after collagenase-induced ICH and 4 hours per day for seven consecutive days. The levels of proinflammatory factors were assessed by ELISA kits and western blotting. Hematoma volume was measured by histological analysis. The effects of PEMFs on phagocytosis of the erythrocytes was observed in cultured BV2 cells.Results: Seven days after ICH, the hematoma volume was significantly reduced in PEMF-treated animals compared to nontreated mice. We found that PEMFs decreased the hematoma volume and the levels of proinflammatory factors after ICH. To evaluate the mechanisms underlying the effects of PEMFs on ICH, we analyzed the transcriptome profile three days after ICH, and we found that PEMFs reversed the changes in inflammation-related pathways and alleviated neurological deficits. Furthermore, PEMFs enhanced the erythrophagocytosis of microglia via CD36. Thus, the PEMF-mediated promotion of neurological functions may at least partly involve anti-inflammatory processes and hematoma clearance.Conclusions: These results suggest that PEMF treatment is a possible adjuvant therapy for ICH patients.

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“…Consistent with the previous studies, we nd the potential link between downregulated Iba-1 + microglia number by IF and improved neurological function at day 3 and 28 after ICH. However, the other major function of microglia is to engulf RBCs and remove cellular debris 30 . Under certain conditions, microglia can also express arginase1 (Arg1), insulinlike growth factor (IGF-1), Ym1 and anti-in ammatory cytokines such as IL-10 and IL-4, which facilitate recovery of CNS injury including ischemic stroke 31 .…”

Section: Discussionmentioning

confidence: 99%

Intermittent Fasting Reduces Neuroinflammation in Intracerebral Hemorrhage Through the Sirt3/Nrf2/HO-1 Pathway

Dai

¹

,

Wei

²

,

Zhang

³

et al. 2021

Preprint

0

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Background: Inflammation contributes to the poor prognosis of intracerebral hemorrhage (ICH). Intermittent fasting (IF) has been shown to be protective against inflammation in multiple pathogenic processes. In the present study, we aimed to investigated the beneficial effects of IF in attenuating neuroinflammation and neurological deficits in a mouse model of ICH and to investigate the underlying mechanism.Methods: ICH was modelled by intrastriatal injection of autologous blood and IF was modelled by every-other-day feeding in male control mice (C57BL6), mice with and microglia specific knockout Sirt3f/f;Cx3cr1-Cre (Sirt3 cKO), and Sirt3f/f (wild-type) mice. Brain tissues and arterial blood were harvested at 1, 3, 7 and 28 days after ICH for immunohistochemistry analysis of Iba-1, DARPP-32 and HO-1, morphological analysis by HE staining and inflammatory factor release tests by ELISA. Motor functions were approached by corner turn and forelimb use asymmetry tests. Fluorescent double-labelled staining of Iba-1 with CD16, Arg1 or Sirt3 was used to provide direct image of co-expression of these molecules in microglia. TUNEL and Nissl staining was performed to evaluate cellular injuries. Results: IF alleviated neurological deficits in both acute and chronic phases after ICH. Morphologically, IF enhanced hematoma clearance, reduced brain edema in acute phase and attenuated striatum atrophy in chronic phase. In addtition, IF decreased the numbers of TUNEL+ cells and increased Nissl+ neuron number at day 1, 3 and 7 after ICH. IF suppressed CD16+Iba-1+ microglia activation at day 3 after ICH and reduced inflammatory releases, such as IL-1β and TNF-α. The above effects of IF were attenuated by microglia Sirt3 deletion partly because of an inhibition of Nrf2/HO-1 signalling pathway. Interestingly, IF increased Iba-1+ microglia number at day 7 which mainly expressed Arg1 while decreased the proinflammatory factor levels. In mice with microglia-specific Sirt3 deletion, the effects of IF on Iba-1+ microglia activation and anti-inflammatory factor expressions were attenuated as compared to wild-type Sirt3f/f mice. Conclusions: IF protects against ICH by suppressing the inflammatory responses via the Sirt3/Nrf2/HO-1 pathway.

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Microglia-derived interleukin-10 accelerates post-intracerebral hemorrhage hematoma clearance by regulating CD36

Cited by 70 publications

References 75 publications

The Prognostic Determinant of Interleukin-10 in Patients with Acute Ischemic Stroke: An Analysis from the Perspective of Disease Management

The Prognostic Determinant of Interleukin-10 in Patients with Acute Ischemic Stroke: An Analysis from the Perspective of Disease Management

Pulsed Electromagnetic Fields Protect Against Brain Injury After Intracerebral Hemorrhage: Involvement Of Anti-Inflammatory Processes And Hematoma Clearance Via CD36

Intermittent Fasting Reduces Neuroinflammation in Intracerebral Hemorrhage Through the Sirt3/Nrf2/HO-1 Pathway

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