scholarly journals Lipopolysaccharide Worsens the Prognosis of Experimental Cerebral Ischemia via Interferon Gamma-Induced Protein 10 Recruit in the Acute Stage

2019 ◽  
Author(s):  
Ping Wang ◽  
Jiaqi Zhang ◽  
Feifei Guo ◽  
Shuang Wang ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Brain Damage ◽  
Interferon Gamma ◽  
Infarct Volume ◽  
Brain Homogenate ◽  
Acute Stage ◽  
Ischemic Brain Injury ◽  
Ppi Network ◽  
Ischemic Brain ◽  
The Brain

Abstract Background: Infection is an important clinical complication facing stroke-patients and triples the risk of death within 30 days post-stroke via mechanisms which are poorly understood . Aims: We tried to explore the mechanisms that infections aggravated the ischemic brain injury after middle cerebral artery occlusion (MCAO). Methods: We used lipopolysaccharide (LPS) as systemic inflammatory stimuli to explore the mechanisms of aggravated ischemic brain injury after Sprague-Dawley male rats subjected to MCAO. Brain damage was evaluated by cerebral blood perfusion, Longa-5 scores, infarct volume and edema degree. Systemic cytokine responses and inflammatory changes in the plasma and brain were analyzed by ELISA kit, RT 2 Profiler TM PCR array, and quantitative real-time PCR.The differential genes were subjected to Gene Ontology enrichment analysis and Protein-protein interaction (PPI) network construction. Results: LPS profoundly aggravated the brain damage after 24 hrs post-MCAO . At the acute stage (Ischemia/ Reperfusion 90min/3h), the brain homogenate gene expression of Interleukin 6 (IL-6), Tumor necrosis factor a ( TNF- a ), Interleukin 1 b (IL-1 b ) and Interferon Gamma-Induced Protein 10 (IP-10) was significantly up-regulated and the contents in plasma and brain homogenate were significantly increased in MCAO and MCAO+LPS group. IP-10 was the only gene with significant difference between MCAO and MCAO+LPS group, which was also in an important position with degrees of ³ 14 in PPI network. Conclusions: It was possible that trace LPS aggravated the ischemic brain injury by induction of excessive IP-10 secretion in the acute stage, leading to excessive inflammatory response, which consequently increased the infarct volume and edema degree 24 hrs post-MCAO.

scholarly journals Lipopolysaccharide worsens the prognosis of experimental cerebral ischemia via interferon gamma-induced protein 10 recruit in the acute stage

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ping Wang ◽  
Jiaqi Zhang ◽  
Feifei Guo ◽  
Shuang Wang ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Brain Damage ◽  
Interferon Gamma ◽  
Infarct Volume ◽  
Brain Homogenate ◽  
Acute Stage ◽  
Ischemic Brain Injury ◽  
Ppi Network ◽  
Ischemic Brain ◽  
The Brain

Abstract Background Infection is an important clinical complication facing stroke-patients and triples the risk of death within 30 days post-stroke via mechanisms which are poorly understood. Aims We tried to explore the mechanisms that inflammation caused by infections aggravated the ischemic brain injury after middle cerebral artery occlusion (MCAO). Methods We used lipopolysaccharide (LPS) as systemic inflammatory stimuli to explore the mechanisms of aggravated ischemic brain injury after Sprague-Dawley male rats subjected to MCAO. Brain damage was evaluated by cerebral blood perfusion, Longa-5 scores, infarct volume and edema degree. Systemic cytokine responses and inflammatory changes in the plasma and brain were analyzed by ELISA kit, RT2 Profiler™ PCR array, and quantitative real-time PCR. The differential genes were subjected to Gene Ontology enrichment analysis and protein–protein interaction (PPI) network construction. Results Lipopolysaccharide profoundly aggravated the brain damage after 24 h post-MCAO. At the acute stage (ischemia/reperfusion 90 min/3 h), the brain homogenate gene expression of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and Interferon gamma-induced protein 10 (IP-10) was significantly up-regulated and the contents in plasma and brain homogenate were significantly increased in MCAO and MCAO + LPS group. IP-10 was the only gene with significant difference between MCAO and MCAO + LPS group, which was also in an important position with degrees of ≥ 14 in PPI network. Conclusions It was possible that trace LPS aggravated the ischemic brain injury by induction of excessive IP-10 secretion in the acute stage, leading to excessive inflammatory response, which consequently increased the infarct volume and edema degree 24 h post-MCAO.

scholarly journals Lipopolysaccharide Worsens the Prognosis of Experimental Cerebral Ischemia via Interferon Gamma-Induced Protein 10 Recruit in the Acute Stage

2019 ◽  
Author(s):  
Ping Wang ◽  
Jiaqi ZHANG ◽  
Feifei GUO ◽  
Shuang Wang ◽  
Yi ZHANG ◽  
...  
Keyword(s):  
Brain Injury ◽  
Interferon Gamma ◽  
Infarct Volume ◽  
Brain Homogenate ◽  
Acute Stage ◽  
Male Rats ◽  
Ischemic Brain Injury ◽  
Ppi Network ◽  
Ischemic Brain ◽  
The Brain

Abstract Background: Infection is an important clinical complication facing stroke-patients and triples the risk of death within 30 days post-stroke via mechanisms which are poorly understood. Aims: We tried to explore the mechanisms that inflammation caused by infections aggravated the ischemic brain injury after middle cerebral artery occlusion (MCAO). Methods: We used lipopolysaccharide (LPS) as systemic inflammatory stimuli to explore the mechanisms of aggravated ischemic brain injury after Sprague-Dawley male rats subjected to MCAO.Brain damage was evaluated by cerebral blood perfusion, Longa-5 scores, infarct volume and edema degree. Systemic cytokine responses and inflammatory changes in the plasma and brain were analyzed by ELISA kit, RT 2 Profiler TM PCR array, and quantitative real-time PCR.The differential genes were subjected to Gene Ontology enrichment analysis and Protein-Protein interaction (PPI) network construction. Results: LPS profoundly aggravated the brain damage after 24 hrs post-MCAO. At the acute stage (Ischemia/Reperfusion 90min/3h), the brain homogenate gene expression of Interleukin 6 (IL-6), Tumor necrosis factor a(TNF-a), Interleukin 1b(IL-1b)and Interferon Gamma-Induced Protein 10 (IP-10)was significantly up-regulated and the contents in plasma and brain homogenate were significantly increased in MCAO and MCAO+LPS group. IP-10 was the only gene with significant difference between MCAO and MCAO+LPS group, which was also in an important position with degrees of ³14 in PPI network. Conclusions: It was possible that trace LPS aggravated the ischemic brain injury by induction of excessive IP-10 secretion in the acute stage, leading to excessive inflammatory response, which consequently increased the infarct volume and edema degree 24 hrs post-MCAO.

Intracerebral Antioxidant Ability of Neonatal Rats After Acute Hypoxic–Ischemic Brain Injury Estimated Using the Brain Homogenate-ESR Method

2015 ◽  
Vol 46 (10) ◽  
pp. 1079-1088
Author(s):  
Akira Nakajima ◽  
Li Yang ◽  
Emiko Matsuda ◽  
Ayako Nagano ◽  
Hiroshi Sameshima ◽  
...  
Keyword(s):  
Brain Injury ◽  
Brain Homogenate ◽  
Ischemic Brain Injury ◽  
Antioxidant Ability ◽  
Neonatal Rats ◽  
Ischemic Brain ◽  
Hypoxic Ischemic Brain Injury ◽  
The Brain

Abstract TMP69: Endoglin Deficiency Exacerbates Ischemic Brain Injury

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Fanxia Shen ◽  
Vincent Degos ◽  
Zhenying Han ◽  
Eun-Jung Choi ◽  
William L. Young ◽  
...  
Keyword(s):  
Brain Injury ◽  
Infarct Volume ◽  
Paradoxical Embolism ◽  
Artery Occlusion ◽  
Vascular Density ◽  
Ischemic Brain Injury ◽  
Myocardial Repair ◽  
Ischemic Brain ◽  
Removal Time ◽  
Adhesive Removal

Background and Objective: Endoglin (Eng) deficiency causes hereditary hemorrhagic telangiectasia (HHT) and impairs myocardial repair. Pulmonary arteriovenous malformations in HHT patients are associated with a high incidence of paradoxical embolism in the cerebral circulation and ischemic brain injury. We hypothesized that Eng deficiency exacerbates ischemic brain injury. Methods: Eng heterozygous ( Eng +/- ) mice and wild type (WT) mice underwent permanent distal middle cerebral artery occlusion (pMCAO). Infarct volume and CD68 + cells were quantified 3 days and vascular density was determined 60 days after pMCAO. Behavior was assessed by corner test and adhesive removal test at 3, 15, 30 and 60 days after pMCAO. Matrix metalloproteinase 9 (Mmp9) and Notch1 expression in bone marrow (BM)-derived macrophages from Eng +/- and WT were analyzed using real-time RT-PCR. Results: Eng +/- mice had a larger Infarct volume than WT mice (22±6% of the affected hemisphere vs. 16±6%, p=0.04). Eng +/- mice had longer adhesive-removal time (p<0.05) and more frequent turning to the lesion side than WT mice at 15, 30 and 60 days (p<0.05) after pMCAO. Both groups had similar numbers of CD68 + cells in the peri-infarct area at 3 days after pMCAO (370±80 vs 338±44 cells/mm 2 , p=0.37), but Eng +/- mice had lower peri-infarct vessel density (417±69 vs 490±52 vessels/mm 2 , p=0.05) at 60 days after pMCAO. Up-regulation of Mmp9 and Notch1 expression in response to VEGF was attenuated in Eng +/- BM-derived macrophages. Conclusions: Endoglin deficiency exacerbated brain injury and behavior dysfunction in mice after pMCAO and was associated with reduced angiogenesis. Although macrophage homing was not affected, reduced expression of two angiogenic-related genes, Mmp9 and Notch1 , by Eng +/- BM-derived macrophages suggests a potential role of these cells in recovery from an ischemic injury.

Chemokines and their receptors in the brain: Pathophysiological roles in ischemic brain injury

Life Sciences ◽  
2003 ◽  
Vol 74 (2-3) ◽  
pp. 321-327 ◽  
Author(s):  
Masabumi Minami ◽  
Masamichi Satoh
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
The Brain

Abstract T P210: Splenectomy Attenuates Sex Differences in Infarct Volume Following Experimental Stroke in Mice

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Jianming Wang ◽  
Sheetal Bodhankar ◽  
Halina Offner ◽  
Stephanie J Murphy
Keyword(s):  
Sex Differences ◽  
Blood Glucose ◽  
Brain Injury ◽  
Infarct Volume ◽  
Blood Gases ◽  
Experimental Stroke ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Male And Female ◽  
Female Mice

It is now increasingly clear that human stroke can have other serious consequences besides brain damage that can impact on patient survival and recovery. For example, many stroke patients succumb to CNS injury-induced immunodepression and fatal infections. Our prior work suggests that evolving cerebral ischemic injury elicits a cycle of injury from brain-to-spleen-to-brain that is strongly influenced by sex. We determined if splenic immunocytes are important in contributing to sex differences in post-ischemic brain injury. Male and female C57BL/6J mice were splenectomized 14 days before experimental stroke. Male and female mice with or without splenectomy (n=9-10 per group) then underwent 60 min of middle cerebral artery occlusion (MCAO) via intraluminal filament. Laser-Doppler flowmetry (LDF) was used to monitor cortical perfusion. All mice were euthanized and brains collected at 96 hours of reperfusion. Infarct volume (% corrected contralateral structure) was determined by image analysis of coronal brain slices stained with 2,3,5-triphenyltetrazolium chloride. Mean arterial blood pressure (MABP), blood gases (pH, P a O 2 , P a CO 2 ), and blood glucose were measured at 30 min MCAO and at 15 min of reperfusion in separate groups of male and female mice with or without splenectomy (n=5 per group). Relative LDF changes (% baseline), MABP, blood gases, and blood glucose during and after MCAO were comparable among the experimental groups. We observed that infarct volume in females (cortex, 41±4%; striatum, 55±6%) was smaller ( P <0.05) compared to males (cortex, 52±3%; striatum, 75±3%) at 96 hours of reperfusion. However, no differences (cortex, P =0.313; striatum, P =0.601) in infarct volume were seen between splenectomized male (cortex, 43±4%; striatum, 51±7%) and female (cortex, 38±4%; striatum, 46±5%) mice. Our data suggest that removal of all splenocyte lineages via splenectomy attenuates sex differences in post-ischemic brain injury. Future studies will evaluate the role of different splenic immunocyte subsets, such as T or B lymphocytes, on male vs. female ischemic brain outcomes. This study was supported by National Institutes of Health grant NS076013.

Dextrorphan Reduces Infarct Volume, Vascular Injury, and Brain Edema after Ischemic Brain Injury

1996 ◽  
Vol 13 (4) ◽  
pp. 215-222 ◽  
Author(s):  
CHENG DU ◽  
RONG HU ◽  
CHUNG Y. HSU ◽  
DENNIS W. CHOI
Keyword(s):  
Brain Injury ◽  
Brain Edema ◽  
Vascular Injury ◽  
Infarct Volume ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

EDA-Containing Fibronectin Aggravates Ischemic Brain Injury In Mice

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 330-330
Author(s):  
Anil Chauhan ◽  
Mohammad M Khan ◽  
Chintan Gandhi ◽  
Neelam Chauhan ◽  
Asgar Zaheer ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Experimental Model ◽  
Vascular Injury ◽  
Laser Doppler Flowmetry ◽  
Infarct Volume ◽  
Neurological Deficits ◽  
Ischemic Brain Injury ◽  
Doppler Flowmetry ◽  
Ischemic Brain

Abstract Abstract 330 Background: Fibronectin (FN) is a dimeric glycoprotein that plays an important role in several cellular processes, such as embryogenesis, malignancy, hemostasis, wound healing and maintenance of tissue integrity. FN is a ligand for many members of the integrin family (e.g. αIIbβ3, α5β1, α4β1, α9β1, αvβ3 and αvβ5) and also binds to thrombosis-related proteins including heparin, collagen and fibrin. FN generates protein diversity as a consequence of alternative processing of a single primary transcript. Two forms of FN exist; soluble plasma FN (pFN), which lacks the alternatively-spliced Extra Domain A (EDA); and insoluble cellular FN (cFN), which contains EDA. FN containing EDA (EDA+FN) is normally absent in plasma of human and mouse but EDA+FN has been found in patients with vascular injury secondary to vasculitis, sepsis, acute major trauma or ischemic stroke. We tested the hypothesis that elevated levels of plasma EDA+FN increase brain injury in an experimental model of ischemic stroke in mice. Model and Method: We used two genetically modified mouse strains: EDA+/+ mice contain optimized spliced sites at both splicing junctions of the EDA exon and constitutively express only EDA+FN, whereas EDA-/- mice contain an EDA-null allele of the EDA exon and express only FN lacking EDA. Control EDAwt/wt mice contain the wild-type FN allele. Transient focal cerebral ischemia was induced by 60 minutes of occlusion of the right middle cerebral artery with a 7.0 siliconized filament in male mice (8-10 weeks in age). Mice were anesthetized with 1–1.5% isoflurane mixed with medical air. Body temperature was maintained at 37°C ± 1.0 using a heating pad. Laser Doppler flowmetry was used to confirm induction of ischemia and reperfusion. At 23 hours after MCAO, mice were evaluated for neurological deficits as a functional outcome and were sacrificed for quantification of infarct volume. For morphometric measurement eight 1 mm coronal sections were stained with 2% triphenyl-2, 3, 4-tetrazolium-chloride (TTC). Sections were digitalized and infarct areas were measured blindly using NIS elements. Result: In EDA+/+ mice the percentage of infarct volume (mean ± SEM: 37.25 ± 4.11, n= 12,) in the ipsilateral (ischemic) hemisphere was increased by approximately two-fold compared to EDA wt/wt mice (mean ± SEM: 22.33 ± 3.39, n=11; P< 0.05, ANOVA) or EDA-/- mice (mean ± SEM: 21.72 ± 2.94, n=9). Regional cerebral blood flow during ischemia was not different among groups as assessed by laser Doppler flowmetry. The percentage increase in infarct volume in the EDA+/+ mice correlated well with severe neurological deficits (motor-deficit assessed by a four-point neurological score scale) compared to EDA wt/wt or EDA-/- mice. Because both thrombosis and inflammation contributes to brain injury during ischemic stroke, we investigated the time to form an occlusive thrombus in ferric-chloride carotid artery injury model by intravital microscopy. EDA+/+ mice demonstrated significantly faster time to occlusion (mean ± SEM: 12.35 ± 1.51 n=12,) compared to EDAwt/wt (Mean ± SEM: 17.27 ± 1.72 min, n=13, P<0.05, ANOVA) or EDA-/- (Mean ± SEM: 15.61 ± 1.76, n=11) mice. Additionally, the inflammatory response in the ischemic region was increased by two fold in EDA+/+ mice compared to EDA wt/wt and EDA-/- mice as sensed by myeloperoxidase activity and immunohistochemical analysis of neutrophils. Conclusion: EDA-containing FN is pro-thrombotic and pro-inflammatory, and aggravates ischemic brain injury in an experimental model of stroke in mice. The presence of EDA+FN in plasma may be a risk factor for vascular injury secondary to ischemic stroke. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Roles of NAD+, PARP-1, and Sirtuins in Cell Death, Ischemic Brain Injury, and Synchrotron Radiation X-Ray-Induced Tissue Injury

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Weihai Ying
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Synchrotron Radiation ◽  
Brain Damage ◽  
Tissue Injury ◽  
Ischemic Brain Injury ◽  
Biological Processes ◽  
Ischemic Brain ◽  
X Ray ◽  
Parp 1

NAD+plays crucial roles in a variety of biological processes including energy metabolism, aging, and calcium homeostasis. Multiple studies have also shown that NAD+administration can profoundly decrease oxidative cell death and ischemic brain injury. A number of recent studies have further indicated that NAD+administration can decrease ischemic brain damage, traumatic brain damage and synchrotron radiation X-ray-induced tissue injury by such mechanisms as inhibiting inflammation, decreasing autophagy, and reducing DNA damage. Our latest study that applies nano-particles as a NAD+carrier has also provided first direct evidence demonstrating a key role of NAD+depletion in oxidative stress-induced ATP depletion. Poly(ADP-ribose) polymerase-1 (PARP-1) and sirtuins are key NAD+-consuming enzymes that mediate multiple biological processes. Recent studies have provided new information regarding PARP-1 and sirtuins in cell death, ischemic brain damage and synchrotron radiation X-ray-induced tissue damage. These findings have collectively supported the hypothesis that NAD+metabolism, PARP-1 and sirtuins play fundamental roles in oxidative stress-induced cell death, ischemic brain injury, and radiation injury. The findings have also supported “the Central Regulatory Network Hypothesis”, which proposes that a fundamental network that consists of ATP, NAD+and Ca2+as its key components is the essential network regulating various biological processes.

Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury

1989 ◽  
Vol 256 (2) ◽  
pp. H589-H593 ◽  
Author(s):  
T. H. Liu ◽  
J. S. Beckman ◽  
B. A. Freeman ◽  
E. L. Hogan ◽  
C. Y. Hsu
Keyword(s):  
Hydrogen Peroxide ◽  
Superoxide Dismutase ◽  
Polyethylene Glycol ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Free Radical Scavengers ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

Superoxide dismutase and catalase enzymatically scavenge superoxide and hydrogen peroxide, respectively. Conjugation of polyethylene glycol to superoxide dismutase (PEG-SOD) or catalase (PEG-CAT) prolongs the circulatory half-life of the native enzymes and enhances their intracellular access. We studied the protective effect of these free radical scavengers on ischemic brain injury using a rat model of focal cerebral ischemia, which is suitable for therapeutic trials. Intravenous administration of PEG-SOD (10,000 U/kg) and PEG-CAT (10,000 U/kg) before ischemia reduced the infarct volume (treatment, 139 +/- 9 mm3, means +/- SE, N = 38; placebo, 182 +/- 8 mm3, n = 37, P less than 0.002). This finding supports the concept that superoxide and hydrogen peroxide contribute to brain injury following focal cerebral ischemia.

Sign in / Sign up

Export Citation Format

Share Document