scholarly journals Activation of the Melanocortin-1 Receptor by NDP-MSH Attenuates Oxidative Stress and Neuronal Apoptosis through PI3K/Akt/Nrf2 Pathway after Intracerebral Hemorrhage in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Siming Fu ◽  
Xu Luo ◽  
Xuan Wu ◽  
Tongyu Zhang ◽  
Linggui Gu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neurological Deficits ◽  
Enzyme Linked Immunosorbent Assay ◽  
Brain Water Content ◽  
Melanocortin 1 Receptor ◽  
Brain Water

Oxidative stress and neuronal apoptosis play crucial roles in secondary brain injury (SBI) after intracerebral hemorrhage (ICH). Recently, Nle4-D-Phe7-α-melanocyte-stimulating hormone (NDP-MSH), a synthetic agonist of the melanocortin-1 receptor (Mc1r), has been proved to inhibit neuroinflammatory in several diseases. This study is aimed at exploring if NDP-MSH could reduce oxidative stress and neuronal apoptosis following ICH, as well as the potential mechanism. A mouse ICH model was induced by autologous blood injection. NDP-MSH was intraperitoneally injected at 1 h after ICH. Mc1r siRNA and PI3K inhibitor LY294002 were administrated to inhibit the expression of Mc1r and phosphorylation of PI3K, respectively. Neurological test, brain water content, enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), immunofluorescence, and Western blot analysis were utilized in this study. The results exhibited that Mc1r was mainly expressed in neurons, and its level in the ipsilateral hemisphere was significantly elevated after ICH. NDP-MSH treatment significantly attenuated the neurological deficits and brain water content 24 hours after ICH, which was accompanied by the inhibition of oxidative stress and neuronal apoptosis. The administration of NDP-MSH after ICH significantly promoted the expression of Mc1r, p-PI3K, p-Akt, and p-Nrf2, followed by an increase of Bcl-2 and reduction of cleaved caspase-3. Conversely, downregulating the expression of Mc1r and phosphorylation of PI3K aggravated the neurological deficits and brain edema at 24 hours after ICH, meanwhile, the effect of NDP-MSH on the expression of Mc1r, p-PI3K, p-Akt, p-Nrf2, Bcl-2, and cleaved caspase 3 was also abolished. In conclusion, our data suggest that the activation of Mc1r by NDP-MSH ameliorates oxidative stress and neuronal apoptosis through the PI3K/Akt/Nrf2 signaling pathway after ICH in mice.

scholarly journals NDP-MSH binding melanocortin-1 receptor ameliorates neuroinflammation and BBB disruption through CREB/Nr4a1/NF-κB pathway after intracerebral hemorrhage in mice

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Xuan Wu ◽  
Siming Fu ◽  
Yun Liu ◽  
Hansheng Luo ◽  
Feng Li ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Autologous Blood ◽  
Neurological Deficits ◽  
Secondary Brain Injury ◽  
Brain Water Content ◽  
Protective Mechanisms ◽  
Neuroprotective Effects ◽  
Melanocortin 1 Receptor ◽  
Brain Water

Abstract Background Neuroinflammation and blood-brain barrier (BBB) disruption are two vital mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Recently, melanocortin-1 receptor (Mc1r) activation by Nle4-D-Phe7-α-MSH (NDP-MSH) was shown to play a neuroprotective role in an experimental autoimmune encephalomyelitis (EAE) mouse model. This study aimed to investigate whether NDP-MSH could alleviate neuroinflammation and BBB disruption after experimental ICH, as well as the potential mechanisms of its neuroprotective roles. Methods Two hundred and eighteen male C57BL/6 mice were subjected to autologous blood-injection ICH model. NDP-MSH, an agonist of Mc1r, was administered intraperitoneally injected at 1 h after ICH insult. To further explore the related protective mechanisms, Mc1r small interfering RNA (Mc1r siRNA) and nuclear receptor subfamily 4 group A member 1 (Nr4a1) siRNA were administered via intracerebroventricular (i.c.v) injection before ICH induction. Neurological test, BBB permeability, brain water content, immunofluorescence staining, and Western blot analysis were implemented. Results The Expression of Mc1r was significantly increased after ICH. Mc1r was mainly expressed in microglia, astrocytes, and endothelial cells following ICH. Treatment with NDP-MSH remarkably improved neurological function and reduced BBB disruption, brain water content, and the number of microglia in the peri-hematoma tissue after ICH. Meanwhile, the administration of NDP-MSH significantly reduced the expression of p-NF-κB p65, IL-1β, TNF-α, and MMP-9 and increased the expression of p-CREB, Nr4a1, ZO-1, occludin, and Lama5. Inversely, the knockdown of Mc1r or Nr4a1 abolished the neuroprotective effects of NDP-MSH. Conclusions Taken together, NDP-MSH binding Mc1r attenuated neuroinflammation and BBB disruption and improved neurological deficits, at least in part through CREB/Nr4a1/NF-κB pathway after ICH.

scholarly journals Role for Target of Rapamycin (mTOR) Signal Pathway in Regulating Neuronal Injury after Intracerebral Hemorrhage

2017 ◽  
Vol 41 (1) ◽  
pp. 145-153 ◽  
Author(s):  
Jie-Ping Wang ◽  
Meng-Yu Zhang
Keyword(s):  
Protein Kinase ◽  
Intracerebral Hemorrhage ◽  
Protein Expression ◽  
Water Content ◽  
Caspase 3 ◽  
Signal Pathway ◽  
Target Of Rapamycin ◽  
Neurological Deficits ◽  
Brain Water Content ◽  
Brain Water

Background/Aims: Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR signal and its downstream products to brain injuries induced by intracerebral hemorrhage (ICH) in rats. Methods: Western Blot analysis was employed to examine the protein expression of mTOR and its downstream pathway and Caspase-3. ELISA was used to measure pro-inflammatory cytokines (PICs) and vascular endothelial growth factor (VEGF). Additionally, neurological Severity Score and brain water content were used to indicate neurological function and brain edema. Results: The protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E–binding protein 4 (4E-BP1), p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in ICH rats compared with controls. Blocking mTOR using rapamycin significantly attenuated upregulation of PICs, namely IL-1β, IL-6 and TNF-α, and Caspase-3 indicating cell apoptosis, and promoted the levels of VEGF and its subtype receptor VEGFR-2 in brain tissues. Moreover, the effects of rapamycin were linked to improvement of neurological deficits and increased brain water content observed in ICH rats. Conclusion: Activation mTOR signal is engaged in pathophysiological process during ICH and blocking mTOR pathway plays a beneficial role in regulating neuronal tissues via PIC, apoptotic Caspase-3 and VEGF mechanisms. This has pharmacological implications to target specific mTOR and its downstream signal pathway for neuronal dysfunction and vulnerability related to ICH.

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 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.

Abstract TP349: Recombinant Slit2 Reduces Brain Water Content and Attenuates Neurobehavioral Deficits Following Intracerebral Hemorrhage in a Murine Model

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Sherrefa R Burchell ◽  
Cesar Reis ◽  
Lingyan Yu ◽  
Ningbo Xu ◽  
John H Zhang ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Time Course ◽  
Leukocyte Migration ◽  
Neurological Deficits ◽  
Brain Water Content ◽  
Stroke Subtype ◽  
Western Blots ◽  
Improved Outcomes ◽  
Brain Water

Introduction and Hypothesis: Intracerebral hemorrhage (ICH) remains the least treatable and most fatal stroke subtype, being associated with significant vascular disruption, which leads to edema development and the recruitment of inflammatory agents. Slit2, one of a family of three large secreted proteins, has been found to regulate cell proliferation, adhesion, and migration through its receptor, roundabout (Robo)1. We have previously found that administration of recombinant Slit2 (rSlit2) improved outcomes after surgical brain injury. Thus, we hypothesized that Slit2, through the Robo1 receptor, could mitigate ICH-induced neuroinflammation by reducing leukocyte migration, thereby decreasing brain water content (BWC), and improving neurobehavior. Methods: ICH was induced in CD-1 mice by collagenase infusion, as previously established. To determine the expression of Slit2 and Robo1 after ICH, a time course profile (3, 6, 12, 24, and 72 hours) of both proteins was developed by Western Blotting. Then, animals were randomly divided into 5 groups: sham, vehicle, 3μg/kg rSlit2, 10μg/kg rSlit2, and 30μg/kg rSlit2. rSlit2 was administered 1h after ICH, and BWC and neurobehavior assessed at 24 and 72 hours. Western blots and immunohistochemistry will be done to evaluate leukocyte infiltration and other inflammatory markers. Results: Endogenous Slit2 and Robo1 were initially decreased, and then increased after ICH, in comparison to sham. Treatment with rSlit2 significantly reduced brain water content at 24 hours and improved neurological scores. At 72h, there was a tendency for improved brain water content and neurobehavior. We further anticipate that rSlit2 treatment will attenuate leukocyte migration to the injury site, as well as inhibit other pro-inflammatory signals, and these through its action on Robo1. Conclusions: Recombinant Slit2 improved outcomes after murine ICH (BWC and neurological deficits). We expect that this occurs through the inhibition of inflammatory signaling.

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.

FGF10 Attenuates Experimental Traumatic Brain Injury through TLR4/MyD88/NF-κB Pathway

2021 ◽  
pp. 1-9
Author(s):  
Qinhan Hou ◽  
Hongmou Chen ◽  
Quan Liu ◽  
Xianlei Yan
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Expression ◽  
Water Content ◽  
Neurological Deficit ◽  
Neuronal Apoptosis ◽  
Neuronal Damage ◽  
Intraventricular Injection ◽  
Brain Water Content ◽  
Brain Water

Traumatic brain injury (TBI) can induce neuronal apoptosis and neuroinflammation, resulting in substantial neuronal damage and behavioral disorders. Fibroblast growth factors (FGFs) have been shown to be critical mediators in tissue repair. However, the role of FGF10 in experimental TBI remains unknown. In this study, mice with TBI were established via weight-loss model and validated by increase of modified neurological severity scores (mNSS) and brain water content. Secondly, FGF10 levels were elevated in mice after TBI, whereas intraventricular injection of Ad-FGF10 decreased mNSS score and brain water content, indicating the remittance of neurological deficit and cerebral edema in TBI mice. In addition, neuronal damage could also be ameliorated by stereotactic injection of Ad-FGF10. Overexpression of FGF10 increased protein expression of Bcl-2, while it decreased Bax and cleaved caspase-3/PARP, and improved neuronal apoptosis in TBI mice. In addition, Ad-FGF10 relieved neuroinflammation induced by TBI and significantly reduced the level of interleukin 1β/6, tumor necrosis factor α, and monocyte chemoattractant protein-1. Moreover, Ad-FGF10 injection decreased the protein expression level of Toll-like receptor 4 (TLR4), MyD88, and phosphorylation of NF-κB (p-NF-κB), suggesting the inactivation of the TLR4/MyD88/NF-κB pathway. In conclusion, overexpression of FGF10 could ameliorate neurological deficit, neuronal apoptosis, and neuroinflammation through inhibition of the TLR4/MyD88/NF-κB pathway, providing a potential therapeutic strategy for brain injury in the future.

scholarly journals Expression of IL-1β, IL-6 and TNF-α in rats with thioacetamide-induced acute liver failure and encephalopathy: correlation with brain edema

2011 ◽  
Vol 5 (2) ◽  
pp. 205-215 ◽  
Author(s):  
Li-Qing Wang ◽  
Heng-Jun Zhou ◽  
Cai-Fei Pan ◽  
Sheng-Mei Zhu ◽  
Lin-Mei Xu
Keyword(s):  
Hepatic Encephalopathy ◽  
Motor Activity ◽  
Water Content ◽  
Brain Edema ◽  
Proinflammatory Cytokines ◽  
Enzyme Linked Immunosorbent Assay ◽  
Brain Water Content ◽  
Tnf Α ◽  
The Relationship ◽  
Brain Water

Abstract Background: Secondary brain edema is a serious complication of hepatic encephalopathy (HE). Recently, it has been reported that proinflammatory cytokines are involved in the pathogenesis of brain edema during HE. Objectives: Observe the dynamic expressions of brain and plasma proinflammatory cytokines in encephalopathy rats, and evaluate the relationship between proinflammatory cytokines and brain edema. Methods: Acute HE rats were induced by intraperitoneal injection of thioacetamide (TAA) in 24 hours intervals for two consecutive days. Then, clinical symptom and stages of hepatic encephalopathy, motor activity counts, index of liver function, and brain water content were observed. The dynamic expressions of IL-1β, IL-6, and TNF-α in plasma and brain tissues were measured with enzyme-linked immunosorbent assay. Results: Typical clinical performances of hepatic encephalopathy were occurred in all TAA-administrated rats. The TAA rats showed lower motor activity counts and higher the index of alanine aminotransferase, aspartate aminotransferase, total bilirubin and ammonia than those in control rats. Brain water content was significantly enhanced in TAA rats compared with the control. The expressions of IL-1β, IL-6, and TNF- α in plasma and brain significantly increased in TAA rats. In addition, the expressions of cerebral proinflammatory cytokines were positively correlated with brain water content but negatively correlated with motor activity counts.Conclusion: Inflammation was involved in the pathogenesis of brain edema during TAA-induced HE.

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 Glymphatic Drainage Blocking Aggravates Brain Edema, Neuroinflammation via Modulating TNF-α, IL-10, and AQP4 After Intracerebral Hemorrhage in Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Xichang Liu ◽  
Gang Wu ◽  
Na Tang ◽  
Li Li ◽  
Cuimin Liu ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neurological Deficits ◽  
Protective Mechanism ◽  
Cervical Lymph Nodes ◽  
Glymphatic System ◽  
Tnf Α ◽  
Active Caspase

Objective: The “Glymphatic” system, a network of perivascular tunnels wrapped by astrocyte endfeet, was reported to be closely associated with the diseases of the central nervous system. Here, we investigated the role of the glymphatic system in intracerebral hemorrhage (ICH) and its protective mechanism.Method: Experimental ICH model was induced by type IV collagenase in rats. Cerebral lymphatic blockage was induced by ligation and removal of cervical lymph nodes. The experimental rats were divided into sham-operated (SO) group, ICH group, and cerebral lymphatic blocking and ICH (ICH + CLB) group. Neurological scores were measured using the Garcia scoring system on the third and seventh day after ICH. Active caspase-3 was immunostained to evaluate neuronal apoptosis. Brain water content was calculated using the dry-wet specific gravity method. The expression of inflammatory factors TNF-α, IL-1β, and IL-10 were detected using ELISA. Aquaporins-4 (AQP-4) and glial fibrillary acidic protein (GFAP) were detected using western blot analysis.Results: The neurological scores of rats in the CLB + ICH group were significantly lower than those in the in ICH group. The number of active caspase-3 neurons was significantly higher in the CLB + ICH group compared to the ICH group. CLB significantly aggravated ICH-induced brain edema 3 d after ICH. There was an increase in the expression of TNF-α, IL-1β, IL-10, AQP-4, GFAP after ICH. The expression of TNF-α was significantly higher in the CLB + ICH group compared to ICH group 3 d after ICH while there was no difference 7 d after ICH. There was no statistical difference in the expression of IL-1β between the ICH group and CLB + ICH group. However, the expression of IL-10 in the CLB + ICH group was significantly lower than that in the ICH group. Lastly, AQP-4 expression was significantly lower in the CLB + ICH group compared to the ICH group while the expression of GFAP was higher in the CLB + ICH group compared to the ICH group.Conclusion: CLB exacerbated cerebral edema, neuroinflammation, neuronal apoptosis and caused neurological deficits in rats with ICH via down-regulating AQP-4, up-regulating inflammatory TNF-α and inhibiting IL-10 expression. The glymphatic drainage system protects against neurologic injury after ICH induction in rats under normal physiological conditions.

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