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 < 0.05), brain water content (BMC) and hemorheology (p < 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 Extracellular Matrix Metalloproteinase Inducer is Associated with Severity of Brain Oedema following Experimental Subarachnoid Haemorrhage in Rats

2012 ◽  
Vol 40 (3) ◽  
pp. 1089-1098 ◽  
Author(s):  
Y Tu ◽  
J Fu ◽  
J Wang ◽  
G Fu ◽  
L Wang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Subarachnoid Haemorrhage ◽  
Water Content ◽  
Brain Oedema ◽  
Sham Group ◽  
Brain Water Content ◽  
Extracellular Matrix Metalloproteinase Inducer ◽  
Protein Levels ◽  
Inhibition Group ◽  
Brain Water

OBJECTIVE: Brain oedema is a major cause of clinical deterioration and death following brain trauma; cellular mechanisms involved in its development remain elusive. This study investigated the role of extracellular matrix metalloproteinase inducer (EMMPRIN) in brain oedema. METHODS: The monofilament puncture model was used to induce subarachnoid haemorrhage. Adult male Sprague—Dawley rats were divided into five groups ( n = 20 per group): sham-operated, sacrificed immediately after surgery (sham group); sacrificed 12, 24 or 72 h after subarachnoid haemorrhage induction (SAH-12, SAH-24 and SAH-72 groups, respectively); treated with EMMPRIN inhibitor immediately after subarachnoid haemorrhage, sacrificed at 24 h (SAH-inhibition group). Mean brain water content, and EMMPRIN mRNA and protein levels, were determined. RESULTS: Compared with the sham group, mean brain water content, EMMPRIN mRNA and protein levels in the SAH-12, SAH-24 and SAH-72 groups increased rapidly and significantly (maximal at 24 h). EMMPRIN inhibition significantly reduced mean brain water content and EMMPRIN mRNA and protein levels in the SAH-inhibition group, compared with the SAH-24 group. CONCLUSIONS: EMMPRIN upregulation may be important in the formation of brain oedema; inhibition of EMMPRIN activity may provide a potential approach to reduce oedema after subarachnoid haemorrhage.

scholarly journals Sheng-Di-Da-Huang Decoction Inhibited Inflammation Expressed in Microglia after Intracerebral Hemorrhage in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Min Cai ◽  
Zhonghai Yu ◽  
Wen Zhang ◽  
Li Yang ◽  
Jun Xiang ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Evans Blue ◽  
Microglial Activation ◽  
Critical Role ◽  
Neurological Deficits ◽  
Secondary Brain Injury ◽  
Brain Water Content ◽  
Evans Blue Extravasation ◽  
Brain Water

Objects. Sheng-Di-Da-Huang Decoction was used as an effective hemostatic agent in ancient China. However, its therapeutic mechanism is still not clear. Inflammatory injury plays a critical role in ICH-induced secondary brain injury. After hemolysis, hematoma components are released, inducing microglial activation via TLR4, which initiates the activation of transcription factors (such as NF-κB) to regulate expression of proinflammatory cytokine genes. This study aimed to verify the anti-inflammatory effects of Sheng-Di-Da-Huang Decoction on ICH rats. Materials and Methods. Intracerebral hemorrhage was induced by injection of bacterial collagenase (0.2 U) in rats. Neurological deficits, brain water content, Evans blue extravasation, expression of TLR4, NF-κB, Iba-1 positive cells (activated microglia), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were examined 1, 3, 7, and 14 days after collagenase injection. MR images were also studied. Results. Sheng-Di-Da-Huang Decoction remarkably improved neurological function, reduced brain water content as well as Evans blue extravasation, downregulated expression of TLR4, NF-κB, TNF-α, and IL-1β, and inhibited microglial activation. Conclusions. Sheng-Di-Da-Huang Decoction reduced inflammation reaction after ICH through inhibited inflammation expressed in microglia.

scholarly journals Role of flunarizine hydrochloride in secondary brain injury following intracerebral hemorrhage in rats

2017 ◽  
Vol 30 (4) ◽  
pp. 413-419 ◽  
Author(s):  
Jianping Niu ◽  
Rui Hu
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Cell Apoptosis ◽  
Akt Pathway ◽  
Secondary Brain Injury ◽  
Brain Water Content ◽  
Hematoma Volume ◽  
Brain Water

This study aimed to explore the role and mechanism(s) of flunarizine hydrochloride in the intracerebral hemorrhage (ICH) rats. The 32 adult male Sprague Dawley (SD) rats were randomly assigned into four groups: control group, sham group, ICH group, and FLU + ICH group. The effects of flunarizine hydrochloride were assessed on the basis of hematoma volume, blood–brain barrier (BBB) integrity, and brain water content in the ICH rat models. The role of flunarizine hydrochloride in cell recovery was assessed by behavioral scores, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot assay. Involvement of PI3K/AKT pathway in exerting the effect of flunarizine hydrochloride was also determined. Results showed that the hematoma volume, BBB integrity, and brain water content were significantly decreased in the FLU + ICH group. Cell apoptosis significantly increased in the ICH model group, while flunarizine hydrochloride decreased this increase. The expressions of glial cell line-derived neurotrophic factor (GDNF), neuroglobin (NGB), and p-AKT were increased after flunarizine hydrochloride treatment in ICH rats. In conclusion, flunarizine hydrochloride has protective effects against ICH by reducing brain injury, cell apoptosis, and the activation of P13K/AKT pathway. These findings provide a theoretical basis for the treatment of flunarizine hydrochloride in ICH.

scholarly journals Rehmannia and Rhubarb Decoction Exerts Neuroprotective Effects on the Blood-brain barrier during Acute Intracerebral Hemorrhage by Downregulating the HMGB1/TLR4/MMP9 signaling pathway

2020 ◽  
Author(s):  
Shan Jiang ◽  
Chun-Mei Li ◽  
Ding-Fang Cai ◽  
Jing-Si Zhang ◽  
Xiao-Fei Yu
Keyword(s):  
Intracerebral Hemorrhage ◽  
Protective Effect ◽  
Water Content ◽  
Signaling Pathway ◽  
Blood Brain Barrier ◽  
Evans Blue ◽  
Brain Barrier ◽  
Brain Water Content ◽  
Acute Intracerebral Hemorrhage ◽  
Brain Water

Abstract Background Blood-brain barrier (BBB) is a gate-keeping system with selective permeability that serves to protect the central nervous system. The underlying neuroprotective mechanism of the BBB during acute intracerebral hemorrhage (ICH) remains poorly understood. Rehmannia and rhubarb decoction (RRD) is a classic traditional Chinese medicine formula that has been extensively applied for hemorrhagic diseases in China. In the present study, the potential protective effects of RRD on the BBB during acute ICH and the underlying mechanism were investigated. Methods The ICH model was established by injection of autologous blood (100 µl) into spontaneously hypertensive rats, which were randomly divided into the following groups: i) Sham; ii) ICH; iii) RRD; iv) TAK-242; v) TAK-242 + RRD; vi) high mobility group box 1 protein (HMGB1) inhibitor ethyl pyruvate (EP); and vii) EP + RRD. Neurological deficits, pathological examination, brain water content, Evans blue(EB) extravasation, immunofluorescence staining and the expression levels of HMGB1, toll-like receptor 4 (TLR4), matrix metalloproteinase 9 (MMP-9), Claudin-5, Occludin and zona occludens − 1 (Zo-1) were subsequently examined in each group on day 3 following operation. In addition, MRI and transmission electron microscopy were also performed to observe the BBB structure. Results RRD treatment markedly improved neurological functions, reduced brain water content and Evans blue extravasation, ameliorated the disruption of BBB and downregulated HMGB1, TLR4 and MMP-9 expression whilst upregulating the expression of Claudin-5, Occludin and Zo-1. Conclusion These results demonstrate that RRD has a protective effect on the BBB in rats during ICH and this protective effect is related to the down-regulation of HMGB1/TLR4/MMP9 signaling pathway.

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.

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 Glibenclamide does not improve outcome following severe collagenase-induced intracerebral hemorrhage in rats

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252584
Author(s):  
Tiffany F. C. Kung ◽  
Cassandra M. Wilkinson ◽  
Christine A. Dirks ◽  
Glen C. Jickling ◽  
Frederick Colbourne
Keyword(s):  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Transient Receptor Potential ◽  
Neurological Deficits ◽  
Brain Water Content ◽  
Adult Rats ◽  
Edema Formation ◽  
Improve Outcome ◽  
Transient Receptor Potential Melastatin ◽  
Brain Water

Intracerebral hemorrhage (ICH) is a devastating insult with few effective treatments. Edema and raised intracranial pressure contribute to poor outcome after ICH. Glibenclamide blocks the sulfonylurea 1 transient receptor potential melastatin 4 (Sur1-Trpm4) channel implicated in edema formation. While glibenclamide has been found to improve outcome and reduce mortality in animal models of severe ischemic stroke, in ICH the effects are less clear. In our previous study, we found no benefit after a moderate-sized bleed, while others have reported benefit. Here we tested the hypothesis that glibenclamide may only be effective in severe ICH, where edema is an important contributor to outcome. Glibenclamide (10 μg/kg loading dose, 200 ng/h continuous infusion) was administered 2 hours post-ICH induced by collagenase injection into the striatum of adult rats. A survival period of 24 hours was maintained for experiments 1–3, and 72 hours for experiment 4. Glibenclamide did not affect hematoma volume (~81 μL) or other safety endpoints (e.g., glucose levels), suggesting the drug is safe. However, glibenclamide did not lessen striatal edema (~83% brain water content), ionic dyshomeostasis (Na+, K+), or functional impairment (e.g., neurological deficits (median = 10 out of 14), etc.) at 24 hours. It also did not affect edema at 72 h (~86% brain water content), or overall mortality rates (25% and 29.4% overall in vehicle vs. glibenclamide-treated severe strokes). Furthermore, glibenclamide appears to worsen cytotoxic edema in the peri-hematoma region (cell bodies were 46% larger at 24 h, p = 0.0017), but no effect on cell volume or density was noted elsewhere. Overall, these findings refute our hypothesis, as glibenclamide produced no favorable effects following severe ICH.

scholarly journals Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

2016 ◽  
Vol 11 (3) ◽  
pp. 675 ◽  
Author(s):  
Najmeh Kabiri ◽  
Mahbubeh Setorki
Keyword(s):  
Water Content ◽  
Sham Group ◽  
Infarct Volume ◽  
Video Clip ◽  
Brain Water Content ◽  
Cerebral Damage ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia And Reperfusion ◽  
Kombucha Tea ◽  
Brain Water

<p>The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99). Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly higher than the Sham group, although right hemispheres in all of the treated groups illustrated higher brain water content than the left ones. Brain anti-oxidant capacity elevated in the ischemic rats treated with Kombucha and in the Sham group. Brain and plasma malondialdehyde concentrations significantly decreased in both of the ischemic groups injected with Kombucha. The findings suggest that Kombucha tea could be useful for the prevention of cerebral damage.</p><p><strong>Video Clip</strong></p><p>Induction of brain ischemia: 5 min 19 sec</p>

scholarly journals Intracerebral Hemorrhage in Mice: Model Characterization and Application for Genetically Modified Mice

2004 ◽  
Vol 24 (5) ◽  
pp. 487-494 ◽  
Author(s):  
Takehiro Nakamura ◽  
Guohua Xi ◽  
Ya Hua ◽  
Timothy Schallert ◽  
Julian T. Hoff ◽  
...  
Keyword(s):  
Brain Injury ◽  
Basal Ganglia ◽  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Gene Knockout ◽  
Brain Water Content ◽  
Male Mice ◽  
Behavioral Deficits ◽  
Autologous Whole Blood ◽  
Brain Water

Gene knockout or transgenic animals may assist in elucidating the mechanisms of brain injury after intracerebral hemorrhage (ICH). However, almost all commercially available transgenic or knockout animals are mice. The purpose of this study was to develop an ICH model in mice and to investigate the influence of gender and complement C5 genetic differences on outcome after ICH. Male and female C57BL/6 mice and C5-deficient and -sufficient control mice were anesthetized and then received an injection of 30 μL autologous whole blood into the right basal ganglia. Brain water content was studied at 1 and 3 days after ICH. Behavioral tests (forelimb use asymmetry and corner turn test) were performed at 1, 3, 7, 14, 21, or 28 days after ICH. In male mice, brain water content was significantly increased in the ipsilateral basal ganglia 1 and 3 days after ICH, compared with saline injection controls ( P>0.01). There were marked neurological deficits 1 and 3 days after ICH, with progressive recovery over 28 days. In contrast, although brain edema and behavioral deficits were similar at 1 day after ICH in female and male mice, female mice showed reduced edema at 3 days and a faster recovery of behavioral deficits after ICH. 17β-estradiol treatment in male mice markedly reduced ICH-induced edema ( P>0.01). Brain water content was significantly increased in C5-deficient mice compared with C5-sufficient at 3 days after ICH ( P>0.05). These findings suggest that the mouse ICH model is a reproducible and feasible model. These results also suggest that gender and complement C5 are factors affecting brain injury after ICH.

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