Abstract TP336: The Intestinal Barrier Dysfunction Induced by Intracerebral Hemorrhage Contributes to the Brain Edema

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Tian Wang ◽  
Bing Han ◽  
Yingjie Han ◽  
Ting Li ◽  
Fenghua Fu
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Intestinal Permeability ◽  
Sham Group ◽  
Intestinal Barrier ◽  
Intestinal Injury ◽  
Brain Water Content ◽  
Barrier Dysfunction ◽  
The Brain ◽  
Brain Water

Background and Purpose: This study aims to investigate whether intracerebral hemorrhage (ICH) can lead to intestinal barrier dysfunction, and whether ICH-induced intestinal injury plays a role in brain edema. Methods: ICH mice model was prepared by an intrastriatal injection of bacterial collagenase. The following parameters were investigated at 3 h, 6 h, 12 h, 1 d, 2 d, 3 d, or 7 d after ICH preparation. Mice were given intragastrically with FITC-dextran and the intestinal permeability was evaluated by serum fluorescence measurement. Serum lipopolysaccharide (LPS) level was assayed with ELISA kits. Ileum and jejunum were stained with hematoxylin and eosin. Intestinal mucosal injuries were graded according to the scoring method (grade 0 to grade 4). Brain water content was evaluated via a wet/dry weight method. Correlations of intestinal injury, intestine permeability, LPS, and brain edema were analyzed using Pearson’s correlation analysis. Results: Compared with the Sham group, Ileum and jejunum damage occurred at 6 h after ICH, and the ICH-induced intestinal injury continued until 7 d. In line with the histopathological findings, the degree of ileum and jejunum injury was significantly increased at 6 h after ICH, showing mostly scores in Grade 1 to Grade 3 ( P < 0.05 or P < 0.01). After 6-h ICH, the intestinal permeability to FITC-dextran was higher compared to the Sham group, and the increase of intestinal permeability lasted 7 d ( P < 0.01). From 6 h to 7 d, serum LPS was significantly augmented ( P < 0.01). The brain content of the ipsilateral hemispheres was increased at 12 h, 1 d, 2 d, and 3 d after ICH ( P < 0.05 or P < 0.01), and the brain content of the contralateral hemispheres was also enhanced at 1 d, 2 d, and 3 d after ICH ( P < 0.01). The ileum and jejunum injury were positively associated with intestine permeability (r = 0.625, P < 0.01, r = 0.465, P < 0.01, respectively). The intestine permeability was positively associated with the serum level of LPS (r =0.585, P < 0.01). The LPS levels were positively associated with brain water content (r = 0.338, P < 0.01). Conclusion: ICH can cause intestinal mucosal injury. Consequently, the increase of intestinal permeability results in the translocation of endotoxins, which contributes to ICH-induced brain edema.

Decreased brain edema after collagenase-induced intracerebral hemorrhage in mice lacking the inducible nitric oxide synthase gene

2009 ◽  
Vol 111 (5) ◽  
pp. 995-1000 ◽  
Author(s):  
Dong Wook Kim ◽  
So-Hyang Im ◽  
Jeong-Yeon Kim ◽  
Dong-Eog Kim ◽  
Goo Taeg Oh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Knockout Mice ◽  
Brain Water Content ◽  
Inos Knockout Mice ◽  
Oxide Synthase ◽  
The Brain ◽  
Brain Water ◽  
Inducible Nitric Oxide

Object Hematoma size and brain edema after intracerebral hemorrhage (ICH) are important prognostic factors. Inducible nitric oxide synthase (iNOS) is induced after cerebral ischemia and is known to be involved in secondary neuronal injury, but its significance in ICH is unknown. The authors tested whether iNOS would influence hematoma size and brain edema after ICH. Methods The authors used C57BL/6 and iNOS knockout mice for all the experiments. Experimental ICH was induced by the intrastriatal stereotactic administration of bacterial collagenase. Brain tissue was obtained at 72 hours after ICH. The volume of hematoma was quantified by spectrophotometric assay, and the brain water content was measured. The investigators also measured blood-brain barrier permeability using Evans blue dye. Results There was no significant difference in hematoma size between the 2 groups. The brain water content of the lesional hemisphere was higher in C57BL/6 mice than in iNOS knockout mice. More Evans blue leakage in the brain was observed in C57BL/6 control mice than in iNOS knockout mice. Immunohistochemistry showed iNOS immunoreactivity in the perihematoma areas of C57BL/6 mice but not in the iNOS knockout mice. Conclusions When hematoma size was similar, iNOS knockout mice had significantly less brain edema than their littermates. These results suggest that iNOS modulation might become an antiedematous therapy for ICH.

scholarly journals Ulinastatin alleviates traumatic brain injury by reducing endothelin-1

2020 ◽  
Vol 12 (1) ◽  
pp. 001-008
Author(s):  
Ting Liu ◽  
Xing-Zhi Liao ◽  
Mai-Tao Zhou
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Water Content ◽  
Brain Edema ◽  
Rat Model ◽  
Neurosurgical Procedures ◽  
Brain Water Content ◽  
The Brain ◽  
Brain Water

Abstract Background Brain edema is one of the major causes of fatality and disability associated with injury and neurosurgical procedures. The goal of this study was to evaluate the effect of ulinastatin (UTI), a protease inhibitor, on astrocytes in a rat model of traumatic brain injury (TBI). Methodology A rat model of TBI was established. Animals were randomly divided into 2 groups – one group was treated with normal saline and the second group was treated with UTI (50,000 U/kg). The brain water content and permeability of the blood–brain barrier were assessed in the two groups along with a sham group (no TBI). Expression of the glial fibrillary acidic protein, endthelin-1 (ET-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry and western blot. Effect of UTI on ERK and PI3K/AKT signaling pathways was measured by western blot. Results UTI significantly decreased the brain water content and extravasation of the Evans blue dye. This attenuation was associated with decreased activation of the astrocytes and ET-1. UTI treatment decreased ERK and Akt activation and inhibited the expression of pro-inflammatory VEGF and MMP-9. Conclusion UTI can alleviate brain edema resulting from TBI by inhibiting astrocyte activation and ET-1 production.

scholarly journals Metabolic Insight Into the Neuroprotective Effect of Tao-He-Cheng-Qi (THCQ) Decoction on ICH Rats Using Untargeted Metabolomics

2021 ◽  
Vol 12 ◽  
Author(s):  
Rui-Pei Yang ◽  
Da-Ke Cai ◽  
Yu-Xing Chen ◽  
Hai-Ning Gang ◽  
Mei Wei ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Amino Acid ◽  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Sham Group ◽  
Neuroprotective Effect ◽  
Treated Group ◽  
Brain Water Content ◽  
Model Group ◽  
Brain Water

Tao-He-Cheng-Qi decoction (THCQ) is an effective traditional Chinese medicine used to treat intracerebral hemorrhage (ICH). This study was performed to investigate the possible neuroprotective effect of THCQ decoction on secondary brain damage in rats with intracerebral hemorrhage and to elucidate the potential mechanism based on a metabolomics approach. Sprague-Dawley (SD) rats were randomly divided into five groups: the sham group, collagenase-induced ICH model group, THCQ low-dose (THCQ-L)-treated group, THCQ moderate-dose (THCQ-M)-treated group and THCQ high-dose (THCQ-H)-treated group. Following 3 days of treatment, behavioral changes and histopathological lesions in the brain were estimated. Untargeted metabolomics analysis with multivariate statistics was performed by using ultrahigh-performance liquid chromatography–mass spectrometry (UPLC-Q-Exactive Orbitrap MS). THCQ treatment at two dosages (5.64 and 11.27 g/kg·d) remarkably improved behavior (p &lt; 0.05), brain water content (BMC) and hemorheology (p &lt; 0.05) and improved brain nerve tissue pathology and inflammatory infiltration in ICH rats. Moreover, a metabolomic analysis demonstrated that the serum metabolic profiles of ICH patients were significantly different between the sham group and the ICH-induced model group. Twenty-seven biomarkers were identified that potentially predict the clinical benefits of THCQ decoction. Of these, 4 biomarkers were found to be THCQ-H group-specific, while others were shared between two clusters. These metabolites are mainly involved in amino acid metabolism and glutamate-mediated cell excitotoxicity, lipid metabolism-mediated oxidative stress, and mitochondrial dysfunction caused by energy metabolism disorders. In addition, a correlation analysis showed that the behavioral scores, brain water content and hemorheology were correlated with levels of serum metabolites derived from amino acid and lipid metabolism. In conclusion, the results indicate that THCQ decoction significantly attenuates ICH-induced secondary brain injury, which could be mediated by improving metabolic disorders in cerebral hemorrhage rats.

scholarly journals Efficacy of Danhong injection on serum concentration of TNF-α, IL-6 and NF-κB in rats with intracerebral hemorrhage

2018 ◽  
Vol 13 (1) ◽  
pp. 77-81
Author(s):  
Chen Peng ◽  
Shibo Duan ◽  
Lou Gang
Keyword(s):  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Control Group ◽  
Brain Water Content ◽  
Model Group ◽  
Danhong Injection ◽  
Tnf Α ◽  
The Brain ◽  
Brain Water ◽  
Time Point

AbstractObjectiveTo investigate the efficacy of Danhong injection on the serum concentration of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) in rats with intracerebral hemorrhage (ICH) and evaluate its therapeutic effects on inflammation and cerebral edema.MethodsSixty male Wistar rats were randomly divided into control, model and Danhong groups with 25 rats in each group. Intracerebral injection of autologous arterial blood was performed on model and Danhong groups in order to establish intracerebral hemorrhage model. Rats in the control group were given the same operation procedure without blood injection. After successfully establishing the intracerebral hemorrhage model, the rats were given Danhong (2ml/kg/d) through intraperitoneal injection. Rats in the control and model groups were given the same amount of normal saline respectively. The brain water content (BWC) and serum level of TNF-α, IL-6 and NF-κB were measured in all groups at the time points of day 1, 3, 5, 7 and 9.ResultsThe neurological deficit score (NDS) were not statistical different in days 1, 3 and 5 between the model and Danhong group (P>0.05); However, on day 7 and 9 after modeling, the NDS in the Danhong group was significant lower than that of the Model group (P<0.05). The brain water content in the model and Danhong groups were significantly elevated compared to control group (P<0.05). The brain water content was significant elevated after modeling in the model and Danhong groups on day 3 and gradually decreased over the next 6 days.The brain water content was significantly higher in the model group for days 3 to 9 compared to the Danhong group (P<0.05). Compared to the model group, the serum NF-κb was significantly lower in the Danhong group for the time point of day 3 and 5 (P<0.05); However, compared to the model group, the serum TNF-α and IL-6 levels in the Danhong group were significantly lower for each time point (P<0.05). Conclusion Danhong injection can reduce cerebral edema in rats with cerebral hemorrhage, and protect the brain nerve function. These effects may be related to its function of regulating serum TNF-α, NF-κB and IL-6 expression.

scholarly journals L-3-n-butylphthalide protect the neuro by reducing inflammation and brain edema in rat intracerebral hemorrhage model

2019 ◽  
Author(s):  
Zhou Zeng ◽  
Xiyu Gong ◽  
Zhiping Hu
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Vehicle Group ◽  
Brain Water Content ◽  
Tnf Α ◽  
Brain Barrier Permeability ◽  
Brain Water

Abstract Background：Previous studies have shown that L-3-n-butylphthalide(NBP), which is a compound found in Apium graveolens Linn seed extracts, could have neuroprotective effects on acute ischemic stroke through anti-inflammation and by reducing brain edema. The pathological inflammatory pathways and consequent brain edema in intracerebral hemorrhage (ICH) share some characteristics with ischemic stroke. Methods：We hypothesized that NBP has anti-inflammatory and therapeutic effects on rats with ICH. ICH was induced by an infusion of bacterial collagenase type IV into the unilateral striatum of anesthetized rats. The therapeutic effect of NBP was measured by assessing neurological function, brain water content, blood-brain barrier permeability, and expression of tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase-9 (MMP-9) around the hematoma 48 hours after surgery. Magnetic resonance imaging (MRI) was performed 4 and 48 hours after ICH induction, and ICH-induced injured area volumes were measured using T2-weighted images. Results： The NBP treatment group performed better in the neurological function test than the vehicle group. Moreover, in comparison with the vehicle group, NBP group showed a lower expanded hematoma volume, brain water content, blood-brain barrier permeability, and TNF-α/ MMP-9 expression level. Conclusions：Our results suggested that NBP have a neuroprotective effect by reducing inflammation and brain edema in rat ICH model. Therefore, our findings also show the potential for clinical application of NBP in the treatment of ICH.

scholarly journals Mechanism of Baicalein in Brain Injury After Intracerebral Hemorrhage by Inhibiting the ROS/NLRP3 Inflammasome Pathway

2021 ◽  
Author(s):  
Xuan Chen ◽  
Yue Zhou ◽  
Shanshan Wang ◽  
Wei Wang
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Factors ◽  
Brain Water Content ◽  
Ros Scavenger ◽  
The Brain ◽  
Brain Water

Abstract Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high disability/mortality. Baicalein has strong anti-inflammatory activity. This study aims to explore the mechanism of baicalein on brain injury after ICH. The model of brain injury after ICH was established by collagenase induction, followed by the evaluation of neurological severity, brain water content, the degenerated neurons, neuronal apoptosis and reactive oxygen species (ROS). The ICH model was treated with baicalein and silencing NLRP3 to detect brain injury. The expression of NLRP3 inflammasome was detected after treatment with ROS scavenger. The expression of oxidative stress markers and inflammatory factors were detected, and the levels of components in NLRP3 inflammasome were detected. Baicalein reduced the damage of nervous system, lesion surface, brain water content and apoptosis. Baicalein inhibited malondialdehyde and increased IL-10 by inhibiting ROS in brain tissue after ICH. Baicalein inhibited the high expression of NLRP3 inflammasome in ICH. ROS scavenger inhibited the NLRP3 inflammatory response by inhibiting ROS levels. Silencing NLRP3 alleviated the brain injury after ICH by inhibiting excessive oxidative stress and inflammatory factors. Overall, baicalein alleviated the brain injury after ICH by inhibiting ROS and NLRP3 inflammasome.

scholarly journals Intestinal Barrier Dysfunction Exacerbates Neuroinflammation via the TLR4 Pathway in Mice With Heart Failure

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun-Yu Huo ◽  
Wan-Ying Jiang ◽  
Ting Yin ◽  
Hai Xu ◽  
Yi-Ting Lyu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Intestinal Permeability ◽  
Intestinal Barrier ◽  
Sham Operation ◽  
Barrier Dysfunction ◽  
Intestinal Alkaline Phosphatase ◽  
Intestinal Barrier Dysfunction ◽  
Junction Protein ◽  
Elevated Expression ◽  
The Brain

AimsThe present study aimed to investigate alterations in neuroinflammation after heart failure (HF) and explore the potential mechanisms.MethodsMale wild-type (WT) and Toll-like receptor 4 (TLR4)-knockout (KO) mice were subjected to sham operation or ligation of the left anterior descending coronary artery to induce HF. 8 weeks later, cardiac functions were analyzed by echocardiography, and intestinal barrier functions were examined by measuring tight junction protein expression, intestinal permeability and plasma metabolite levels. Alterations in neuroinflammation in the brain were examined by measuring microglial activation, inflammatory cytokine levels and the proinflammatory signaling pathway. The intestinal barrier protector intestinal alkaline phosphatase (IAP) and intestinal homeostasis inhibitor L-phenylalanine (L-Phe) were used to examine the relationship between intestinal barrier dysfunction and neuroinflammation in mice with HF.ResultsEight weeks later, WT mice with HF displayed obvious increases in intestinal permeability and plasma lipopolysaccharide (LPS) levels, which were accompanied by elevated expression of TLR4 in the brain and enhanced neuroinflammation. Treatment with the intestinal barrier protector IAP significantly attenuated neuroinflammation after HF while effectively increasing plasma LPS levels. TLR4-KO mice showed significant improvements in HF-induced neuroinflammation, which was not markedly affected by intestinal barrier inhibitors or protectors.ConclusionHF could induce intestinal barrier dysfunction and increase gut-to-blood translocation of LPS, which could further promote neuroinflammation through the TLR4 pathway.

scholarly journals Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 940
Author(s):  
Li Wu ◽  
Yuqiu Han ◽  
Zhipeng Zheng ◽  
Shuai Zhu ◽  
Jun Chen ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Intestinal Barrier ◽  
Behavioral Performance ◽  
High Fat ◽  
Barrier Dysfunction ◽  
Obeticholic Acid ◽  
Promising Agent ◽  
Serum Biochemical ◽  
Lipid Metabolites ◽  
The Brain

Anxiety is one of the complications of metabolic disorders (MDs). Obeticholic acid (OCA), the bile acids (BAs) derivative, is a promising agent for improving MDs in association with gut dysbiosis. Yet, its protective effect on MDs-driven anxiety remains unknown. Here, we assessed the serum biochemical parameters and behavioral performance by open field and Morris water maze tests in HFHS diet-induced MDs mice after OCA intervention for nine and 18 weeks. Moreover, antibiotics intervention for microbial depletion was conducted simultaneously. We found that OCA treatment inhibited the initiation and progression of anxiety in HFHS diet-MDs mice via a microbiota–BAs–brain axis: OCA decreased the neuroinflammatory microglia and IL-1β expression in the hippocampus, reversed intestinal barrier dysfunction and serum proinflammatory LPS to a normal level, modified the microbial community, including the known anxiety-related Rikenellaceae and Alistipes, and improved the microbial metabolites especially the increased BAs in feces and circulation. Moreover, the OCA-reversed bile acid taurocholate linked disordered serum lipid metabolites and indole derivatives to anxiety as assessed by network analysis. Additionally, microbial depletion with antibiotics also improved the anxiety, microgliosis and BAs enrichment in the experimental MDs mice. Together, these findings provide microbiota–BAs–brain axis as a novel therapeutic target for MDs-associated neuropsychiatric disorders.

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