scholarly journals IL (Interleukin)-15 Bridges Astrocyte-Microglia Crosstalk and Exacerbates Brain Injury Following Intracerebral Hemorrhage

Stroke ◽  
2020 ◽  
Vol 51 (3) ◽  
pp. 967-974 ◽  
Author(s):  
Samuel X. Shi ◽  
Yu-Jing Li ◽  
Kaibin Shi ◽  
Kristofer Wood ◽  
Andrew F. Ducruet ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Autologous Blood ◽  
Brain Slices ◽  
Neurological Deficits ◽  
Transgenic Mouse Line ◽  
Il Interleukin ◽  
Targeted Expression ◽  
Interleukin 15

Background and Purpose— Microglia are among the first cells to respond to intracerebral hemorrhage (ICH), but the mechanisms that underlie their activity following ICH remain unclear. IL (interleukin)-15 is a proinflammatory cytokine that orchestrates homeostasis and the intensity of the immune response following central nervous system inflammatory events. The goal of this study was to investigate the role of IL-15 in ICH injury. Methods— Using brain slices of patients with ICH, we determined the presence and cellular source of IL-15. A transgenic mouse line with targeted expression of IL-15 in astrocytes was generated to determine the role of astrocytic IL-15 in ICH. The expression of IL-15 was controlled by a glial fibrillary acidic protein promoter (GFAP-IL-15 tg ). ICH was induced by intraparenchymal injection of collagenase or autologous blood. Results— In patients with ICH and wild-type mice subjected to experimental ICH, we found a significant upregulation of IL-15 in astrocytes. In GFAP-IL-15 tg mice, we found that astrocyte-targeted expression of IL-15 exacerbated brain edema and neurological deficits following ICH. This aggravated ICH injury in GFAP-IL-15 tg mice is accompanied by increased microglial accumulation in close proximity to astrocytes in perihematomal tissues. Additionally, microglial expression of CD86, IL-1β, and TNF-α is markedly increased in GFAP-IL-15 tg mice following ICH. Furthermore, depletion of microglia using a colony stimulating factor 1 receptor inhibitor diminishes the exacerbation of ICH injury in GFAP-IL-15 tg mice. Conclusions— Our findings identify IL-15 as a mediator of the crosstalk between astrocytes and microglia that exacerbates brain injury following ICH.

scholarly journals Role of Lipocalin-2 in Brain Injury after Intracerebral Hemorrhage

2015 ◽  
Vol 35 (9) ◽  
pp. 1454-1461 ◽  
Author(s):  
Wei Ni ◽  
Mingzhe Zheng ◽  
Guohua Xi ◽  
Richard F Keep ◽  
Ya Hua
Keyword(s):  
Brain Injury ◽  
Basal Ganglia ◽  
Intracerebral Hemorrhage ◽  
Autologous Blood ◽  
Sham Operation ◽  
Intracerebral Injection ◽  
Lipocalin 2 ◽  
Brain Swelling ◽  
Male Adult

Lipocalin-2 (LCN2) is a siderophore-binding protein involved in cellular iron transport and neuroinflammation. Both iron and inflammation are involved in brain injury after intracerebral hemorrhage (ICH) and this study examined the role of LCN2 in such injury. Male adult C57BL/6 wild-type (WT) or LCN2-deficient (LCN2-/-) mice had an intracerebral injection of autologous blood or FeCl2. Control animals had a sham operation or saline injection. T2-weighted magnetic resonance imaging and behavioral tests were performed at days 1, 3, 7, 14, and 28 after injection. In WT mice, brain LCN2 levels were increased in the ipsilateral basal ganglia after ICH or iron injection. Lipocalin-2-positive cells were astrocytes, microglia, neurons, and endothelial cells. Intracerebral hemorrhage resulted in a significant increase in ferritin expression in the ipsilateral basal ganglia. Compared with WT mice, ICH caused less ferritin upregulation, microglia activation, brain swelling, brain atrophy, and neurologic deficits in LCN2-/- mice ( P < 0.05). The size of the lesion induced by FeCl2 injection as well as the degree of brain swelling and blood–brain barrier disruption were also less in LCN2-/- mice ( P < 0.05). These results suggest a role of LCN2 in enhancing brain injury and iron toxicity after ICH.

The role of complement in brain injury following intracerebral hemorrhage: A review

2021 ◽  
pp. 113654
Author(s):  
Katherine Holste ◽  
Fan Xia ◽  
Hugh J.L. Garton ◽  
Shu Wan ◽  
Ya Hua ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage

Abstract TP351: Axl/Mer Receptor Tyrosine Kinase Mediates Erythrophagocytosis-Induced Macrophage Reparative Phenotype and Brain Recovery in Experimental Intracerebral Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Che-Feng Chang ◽  
Brittany A Thomas ◽  
Michael Askenase ◽  
Arthur F Steinschneider ◽  
Youxi Ai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Autologous Blood ◽  
Phenotypic Change ◽  
Macrophage Phenotype ◽  
Double Knockout ◽  
Brain Recovery

Introduction: Local inflammation contributes to both brain injury and recovery after intracerebral hemorrhage (ICH). Our previous studies have shown brain-infiltrating macrophages (BIMs) aggravate early brain injury after ICH; however, BIMs increase scavenger receptor CD36 levels over time, and hematoma clearance is delayed in the absence of BIMs. The mechanism that mediates BIMs phenotypic change in the ICH brain is elusive. In this study, we delineate the dynamic transcriptome profile of BIMs after ICH and test potential mediator that might modulate BIMs polarity in ICH. Methods: Autologous blood injection ICH model and thrombin-treated bone marrow-derived macrophages (BMDM) were used to mimic ICH in vivo and in vitro . BIMs were isolated by FACS, and the 780 transcriptome of BIMs were determined using NanoString. Flow cytometry and RT-qPCR were performed to detect the frequency of phosphatidylserine-positive (eryptotic) RBCs and to assess BIMs phenotype in the perihematomal tissue. Erythrophagocytosis of eryptotic RBCs was identified by immunofluorescence and microscopy. Neurologic deficit was evaluated by cylinder test. Axl/Mer receptor tyrosine kinase double knockout (AM DKO) mice, AM DKO bone-marrow chimeras, and AM DKO BMDM were used to evaluate the function of Axl/Mer on macrophage phenotype and on brain recovery after ICH. Results: BIMs highly expressed proinflammatory transcripts such as cd86 , tlr2 , nlrp3 , and tnf at days 1 and 3 post-ICH; these were decreased at days 7 and 10. Transcripts relevant to efferocytosis ( axl ) and lysosome formation ( cd63 ) increased from days 3 to 10 post-ICH. At days 1 and 3, phosphatidylserine levels was increased on RBCs in the ICH brain. Engulfment of eryptotic RBCs reduced proinflammatory phenotype of BMDM. Thrombin-stimulated AM DKO BMDM had reduced erythrophagocytosis ability and increased tnf and il-6 gene expression. AM DKO mice and AM DKO chimeras had low CD36 and high MHC II levels on BIMs and had worse functional outcome after ICH. Conclusions: BIMs initially express proinflammatory phenotype and then switch to a reparative phenotype after ICH. Axl/Mer is involved in regulation of macrophage polarity through modulating erythrophagocytosis ability and contributes to ICH brain recovery.

scholarly journals Correction to: Intracerebral Hemorrhage–Induced Brain Injury in Rats: the Role of Extracellular Peroxiredoxin 2

2019 ◽  
Vol 11 (6) ◽  
pp. 1364-1365
Author(s):  
Liheng Bian ◽  
Jingwei Zhang ◽  
Ming Wang ◽  
Richard F. Keep ◽  
Guohua Xi ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Peroxiredoxin 2

scholarly journals Intracerebral Hemorrhage–Induced Brain Injury in Rats: the Role of Extracellular Peroxiredoxin 2

2019 ◽  
Vol 11 (2) ◽  
pp. 288-295 ◽  
Author(s):  
Liheng Bian ◽  
Jingwei Zhang ◽  
Ming Wang ◽  
Richard F. Keep ◽  
Guohua Xi ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Peroxiredoxin 2

scholarly journals Spreading depolarizations in patients with spontaneous intracerebral hemorrhage: Association with perihematomal edema progression

2016 ◽  
Vol 37 (5) ◽  
pp. 1871-1882 ◽  
Author(s):  
Raimund Helbok ◽  
Alois Josef Schiefecker ◽  
Christian Friberg ◽  
Ronny Beer ◽  
Mario Kofler ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Electrode Placement ◽  
Secondary Brain Injury ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Strip Electrode ◽  
Hematoma Evacuation ◽  
Perihematomal Edema ◽  
Pathophysiologic Mechanisms

Pathophysiologic mechanisms of secondary brain injury after intracerebral hemorrhage and in particular mechanisms of perihematomal-edema progression remain incompletely understood. Recently, the role of spreading depolarizations in secondary brain injury was established in ischemic stroke, subarachnoid hemorrhage and traumatic brain injury patients. Its role in intracerebral hemorrhage patients and in particular the association with perihematomal-edema is not known. A total of 27 comatose intracerebral hemorrhage patients in whom hematoma evacuation and subdural electrocorticography was performed were studied prospectively. Hematoma evacuation and subdural strip electrode placement was performed within the first 24 h in 18 patients (67%). Electrocorticography recordings started 3 h after surgery (IQR, 3–5 h) and lasted 157 h (median) per patient and 4876 h in all 27 patients. In 18 patients (67%), a total of 650 spreading depolarizations were observed. Spreading depolarizations were more common in the initial days with a peak incidence on day 2. Median electrocorticography depression time was longer than previously reported (14.7 min, IQR, 9–22 min). Postoperative perihematomal-edema progression (85% of patients) was significantly associated with occurrence of isolated and clustered spreading depolarizations. Monitoring of spreading depolarizations may help to better understand pathophysiologic mechanisms of secondary insults after intracerebral hemorrhage. Whether they may serve as target in the treatment of intracerebral hemorrhage deserves further research.

Role of AT1 receptors and NAD(P)H oxidase in diabetes-aggravated ischemic brain injury

2004 ◽  
Vol 286 (6) ◽  
pp. H2442-H2451 ◽  
Author(s):  
Ikuyo Kusaka ◽  
Gen Kusaka ◽  
Changman Zhou ◽  
Mami Ishikawa ◽  
Anil Nanda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Focal Cerebral Ischemia ◽  
Lipid Hydroperoxide ◽  
Neurological Deficits ◽  
Sprague Dawley

The objective of the present study was to examine the role of the angiotensin II type 1 receptor (AT1-R) in the diabetes-aggravated oxidative stress and brain injury observed in a rat model of combined diabetes and focal cerebral ischemia. Diabetes was induced by an injection of streptozotoxin (STZ; 55 mg/kg iv) at 8 wk of age. Two weeks after the induction of diabetes, some animals received continuous subcutaneous infusion of the AT1-R antagonist candesartan (0.5 mg·kg−1·day−1) for 14 days. Focal cerebral ischemia, induced by middle cerebral artery occlusion/reperfusion (MCAO), was conducted at 4 wk after STZ injection. Male Sprague-Dawley rats ( n = 189) were divided into five groups: normal control, diabetes, MCAO, diabetes + MCAO, and diabetes + MCAO + candesartan. The major observations were that 1) MCAO produced typical cerebral infarction and neurological deficits at 24 h that were accompanied by elevation of NAD(P)H oxidase gp91phox and p22phox mRNAs, and lipid hydroperoxide production in the ipsilateral hemisphere; 2) diabetes enhanced NAD(P)H oxidase gp91phox and p22phox mRNA expression, potentiated lipid peroxidation, aggravated neurological deficits, and enlarged cerebral infarction; and 3) candesartan reduced the expression of gp91phox and p22phox, decreased lipid peroxidation, lessened cerebral infarction, and improved the neurological outcome. We conclude that diabetes exaggerates the oxidative stress, NAD(P)H oxidase induction, and brain injury induced by focal cerebral ischemia. The diabetes-aggravated brain injury involves AT1-Rs. We have shown for the first time that candesartan reduces brain injury in a combined model of diabetes and cerebral ischemia.

scholarly journals Role of PGE2 EP1 Receptor in Intracerebral Hemorrhage-Induced Brain Injury

2013 ◽  
Vol 24 (4) ◽  
pp. 549-559 ◽  
Author(s):  
Nilendra Singh ◽  
Bo Ma ◽  
Christopher Charles Leonardo ◽  
Abdullah Shafique Ahmad ◽  
Shuh Narumiya ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Ep1 Receptor
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