miR-7-5p Affects Brain Edema After Intracerebral Hemorrhage and Its Possible Mechanism

Objective: To explore the relationship between miR-7-5p and brain edema after intracerebral hemorrhage and the role of butylphthalide (NBP) in brain edema after intracerebral hemorrhage.Method: Routine blood testing, C-reactive protein results, and computed tomography data were collected 1, 7, and 14 days after intracerebral hemorrhage in six patients. Levels of MMP-9, ZO-1, occludin, IL-6, TNF-α, and miR-7-5p were detected in each patient's serum. Sixty male Sprague–Dawley rats were randomly divided into sham operation, intracerebral hemorrhage, and NBP treatment groups. Dry–wet weight was used to assess brain edema, and Evans blue staining was used to assess the permeability of the blood–brain barrier. Expression levels of IL-6, TNF-α, ZO-1 and occludin, PI3K, AKT, p-AKT, AQP4, and miR-7-5p were analyzed in the rat brains.Result: The blood neutrophil–lymphocyte ratio (NLR) on day 1 was associated with the area of brain edema on day 7. The expression of miR-7-5p decreased after intracerebral hemorrhage, and as a result, the inhibition of the PI3K/AKT pathway was weakened. The decreased inhibition of the PI3K/AKT pathway resulted in an increase in AQP4 expression, which further aggravated brain edema. NBP can upregulate the expression of miR-7-5p, affecting these pathways to reduce brain edema.Conclusion: After intracerebral hemorrhage, miR-7-5p expression in brain tissue is reduced, which may increase the expression of AQP4 by activating the PI3K/AKT pathway. NBP can inhibit this process and reduce brain edema.

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Ammonia reduction with ornithine phenylacetate restores brain eNOS activity via the DDAH-ADMA pathway in bile duct-ligated cirrhotic rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00097.2011 ◽

2012 ◽

Vol 302 (1) ◽

pp. G145-G152 ◽

Cited By ~ 29

Author(s):

Vairappan Balasubramaniyan ◽

Gavin Wright ◽

Vikram Sharma ◽

Nathan A. Davies ◽

Yalda Sharifi ◽

...

Keyword(s):

Bile Duct ◽

Protein Expression ◽

Ammonia Concentration ◽

Sham Operation ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Duct Ligation ◽

Tnf Α ◽

No Signaling ◽

Brain Water

Ammonia is central in the pathogenesis of hepatic encephalopathy, which is associated with dysfunction of the nitric oxide (NO) signaling pathway. Ornithine phenylacetate (OP) reduces hyperammonemia and brain water in cirrhotic animals. This study aimed to determine whether endothelial NO synthase activity is altered in the brain of cirrhotic animals, whether this is associated with changes in the endogenous inhibitor, asymmetric-dimethylarginine (ADMA) and its regulating enzyme, dimethylarginine-dimethylaminohydrolase (DDAH-1), and whether these abnormalities are restored by ammonia reduction using OP. Sprague-Dawley rats were studied 4-wk after bile duct ligation (BDL) ( n = 16) or sham operation ( n = 8) and treated with placebo or OP (0.6 g/kg). Arterial ammonia, brain water, TNF-α, plasma, and brain ADMA were measured using standard techniques. NOS activity was measured radiometrically, and protein expression for NOS enzymes, ADMA, DDAH-1, 4-hydroxynonenol (4HNE), and NADPH oxidase (NOX)-1 were measured by Western blotting. BDL significantly increased arterial ammonia ( P < 0.0001), brain water ( P < 0.05), and brain TNF-α ( P < 0.01). These were reduced significantly by OP treatment. The estimated eNOS component of constitutive NOS activity was significantly lower ( P < 0.05) in BDL rat, and this was significantly attenuated in OP-treated animals. Brain ADMA levels were significantly higher and brain DDAH-1 significantly lower in BDL compared with sham ( P < 0.01) and restored toward normal following treatment with OP. Brain 4HNE and NOX-1 protein expression were significantly increased in BDL rat brain, which were significantly decreased following OP administration. We show a marked abnormality of NO regulation in cirrhotic rat brains, which can be restored by reduction in ammonia concentration using OP.

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Preconditioning with hyperbaric oxygen attenuates brain edema after experimental intracerebral hemorrhage

Neurosurgical FOCUS ◽

10.3171/foc.2007.22.5.14 ◽

2007 ◽

Vol 22 (5) ◽

pp. 1-6 ◽

Cited By ~ 21

Author(s):

Zhiyong Qin ◽

Shuijiang Song ◽

Guohua Xi ◽

Robert Silbergleit ◽

Richard F. Keep ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Brain Edema ◽

Hyperbaric Oxygen ◽

Mapk Pathway ◽

Autologous Blood ◽

Neurosurgical Procedures ◽

Sprague Dawley ◽

Edema Formation ◽

Group 2 ◽

Brain Edema Formation

Object Preconditioning with hyperbaric oxygen (HBO2) reduces ischemic brain damage. Activation of p44/42 mitogen-activated protein kinases (p44/42 MAPK) has been associated with preconditioning-induced brain ischemic tolerance. This study investigated if preconditioning with HBO2 protects against intracerebral hemorrhage (ICH)–induced brain edema formation and examined the role of p44/42 MAPK in such protection. Methods The study had three experimental groups. In Group 1, Sprague-Dawley rats received two, three, or five consecutive sessions of preconditioning with HBO2 (3 ata, 100% xygen, 1 hour daily). Twenty-four hours after preconditioning with HBO2, rats received an infusion of autologous blood into the caudate. They were killed 1 or 3 days later for brain edema measurement. Rats in Group 2 received either five sessions of preconditioning with HBO2 or control pretreatment and were killed 24 hours later for Western blot and immunohistochemical analyses. In Group 3, rats received an intracau-date injection of PD098059 (an inhibitor of p44/42 MAPK activation) before the first of five sessions of preconditioning with HBO2. Twenty-four hours after the final preconditioning with HBO2, rats received an intracaudate blood infusion. Brain water content was measured 24 hours after ICH. Results Fewer than five sessions of preconditioning with HBO2 did not significantly attenuate brain edema after ICH. Five sessions of preconditioning with HBO2 reduced perihematomal edema 24 and 72 hours after ICH (p < 0.05). Strong p44/42 MAPK immunoreactivity was detected in the basal ganglia 24 hours after preconditioning with BO2. Intracaudate infusion of PD098059 abolished HBO2preconditioning–induced protection against ICH-induced brain edema formation. Conclusions Preconditioning with HBO2 protects against brain edema formation following ICH. Activation of the p44/42 MAPK pathway contributes to that protection. Preconditioning with HBO2 may be a way of limiting brain injury during invasive neurosurgical procedures that cause bleeding.

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

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.784154 ◽

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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Enriched Environment Regulates Dendritic Cells to Alleviate Inflammation in Cerebral Infarction Lesions

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/1574109 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Zhenzhen Zhong ◽

Ping Xu ◽

Jun Wen ◽

Xiangdong Li ◽

Xiaobo Zhang

Keyword(s):

Dendritic Cells ◽

Cerebral Infarction ◽

Brain Tissue ◽

Neuronal Injury ◽

Enriched Environment ◽

Sham Operation ◽

Dependent Manner ◽

Sprague Dawley ◽

Sham Operation Group ◽

Tnf Α

Objective. The aim was to investigate the role that enriched environment (EE) plays in the regulation of inflammation in cerebral infarction (CI) lesions and further explore the relationship between this regulation and dendritic cells (DCs). Methods. 72 Sprague-Dawley rats were randomly divided into sham operation group (CON group, n = 24 ) and CI model group ( n = 48 ). On completion of the establishment of CI rat models by Longa’s method, rats in the models group were further assigned to standard environment group (NC group, n = 24 ) and EE group ( n = 24 ). HE staining was utilized for evaluation of neuronal injury in the lesions. The number of CD74- and integrin αE-positive cells was detected by immunofluorescence. The expression of the IL-1β, IL-6, and TNF-α in the brain tissue and serum of rats was measured by immunohistochemistry and ELISA, respectively. Results. In comparison with the CON group, the NC and EE groups showed significant increases in neuronal injury, CD74- and Integrin αE-positive cells, DC content, as well as IL-1β, IL-6, and TNF-α expression in brain tissue and serum. According to the further comparison between the NC group and EE group, the latter showed decreases in each indicator, and these decreases were in a time-dependent manner. Conclusion. EE avoids the accumulation of DCs in the lesions and reduces the contents of IL-1β, IL-6, and TNF-α, consequently promoting the recovery of CI. And better recovery results can be obtained through increasing the time to stay in EE.

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Estrogen therapy for experimental intracerebral hemorrhage in rats

Journal of Neurosurgery ◽

10.3171/jns.2005.103.1.0097 ◽

2005 ◽

Vol 103 (1) ◽

pp. 97-103 ◽

Cited By ~ 41

Author(s):

Takehiro Nakamura ◽

Ya Hua ◽

Richard F. Keep ◽

Jung-Weon Park ◽

Guohua Xi ◽

...

Keyword(s):

Brain Injury ◽

Intracerebral Hemorrhage ◽

Brain Edema ◽

Estrogen Therapy ◽

Female Rats ◽

Male Rats ◽

Neurological Deficits ◽

Sprague Dawley ◽

Autologous Whole Blood ◽

17Β Estradiol

Object The aims of this study were to determine the following: whether there are sex differences in intracerebral hemorrhage (ICH) induced brain injury in rats, whether delayed administration of 17β-estradiol can reduce ICH-induced brain damage, and whether these effects are estrogen receptor (ER)-dependent. Methods Male and female Sprague—Dawley rats received an infusion of 100 µl autologous whole blood into the right basal ganglia. Twenty-four hours later the rats were killed. The effects of 17β-estradiol on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Both ER-α and hemeoxygenase (HO)-1 were investigated through Western blot and immunohistochemical analysis. Brain edema was significantly less severe in female compared with that in male rats. The ER antagonist ICI 182,780 exacerbated ICH-induced brain edema in female but not in male rats, indicating that ER-α activation during ICH is protective in female rats. Administration of exogenous 17β-estradiol in male, but not in female, rats significantly attenuated brain edema, neurological deficits, and ICH-induced changes in HO-1 when given 2 hours after hemorrhage. The effects of exogenous 17β-estradiol occurred through an ER-independent mechanism. Conclusions Results in this study indicate that 17β-estradiol could be a potential therapeutic agent for ICH.

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CXCR2 is involved in pulmonary intravascular macrophage accumulation and angiogenesis in a rat model of hepatopulmonary syndrome

Clinical Science ◽

10.1042/cs20160593 ◽

2016 ◽

Vol 131 (2) ◽

pp. 159-168 ◽

Cited By ~ 5

Author(s):

Xujiong Li ◽

Yunxia Chen ◽

Yongli Chang ◽

Shufen Li ◽

Zhongfu Zhao ◽

...

Keyword(s):

Normal Saline ◽

Venous Pressure ◽

Hepatopulmonary Syndrome ◽

Sham Operation ◽

Sprague Dawley ◽

Common Bile Duct Ligation ◽

Pulmonary Tissue ◽

Post Surgery ◽

Duct Ligation ◽

Tnf Α

Hepatopulmonary syndrome (HPS) is a lung complication in various liver diseases, with high incidence, poor prognosis and no effective non-surgical treatments in patients with hepatocirrhosis. Therefore, assessing HPS pathogenesis to explore proper therapy strategies is clinically relevant. In the present study, male Sprague–Dawley rats underwent sham operation or common bile duct ligation (CBDL). Two weeks post-surgery, the following groups were set up for 2 weeks of treatment: sham + normal saline, CBDL + CXCR2 antagonist SB225002, CBDL + tumour necrosis factor α (TNF-α) antagonist PTX and CBDL + normal saline groups. Liver and lung tissues were collected after mean arterial pressure (MAP) and portal venous pressure (PVP) measurements. Haematoxylin and eosin (H&E) staining (lung) and Masson staining (liver) were performed for pathological analyses. Finally, pulmonary tissue RNA and total protein were assessed for target effectors. The mRNA and protein levels of CXCR2 were significantly increased in the pulmonary tissue of CBDL rats. What's more, CXCR2 inhibition by SB225002 reduced the expression of CD68 and von Willebrand factor (vWf) in CBDL rats. Importantly, CXCR2 inhibition suppressed the activation of Akt and extracellular signal-regulated kinase (ERK) in CBDL rats. Antagonization of TNF-α with PTX down-regulated the expression of CXCR2. During HPS pathogenesis in rats, CXCR2 might be involved in the accumulation of pulmonary intravascular macrophages and angiogenesis, possibly by activating Akt and ERK, with additional regulation by TNF-α that enhanced pulmonary angiogenesis by directly acting on the pulmonary tissue. Finally, the present study may provide novel targets for the treatment of HPS.

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Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats

Journal of Neurosurgery ◽

10.3171/jns.1998.89.6.0991 ◽

1998 ◽

Vol 89 (6) ◽

pp. 991-996 ◽

Cited By ~ 236

Author(s):

Guohua Xi ◽

Richard F. Keep ◽

Julian T. Hoff

Keyword(s):

Intracerebral Hemorrhage ◽

Brain Edema ◽

Sprague Dawley ◽

Edema Formation ◽

Content Type ◽

Packed Red Blood Cells ◽

Brain Water ◽

Packed Rbcs ◽

Brain Edema Formation ◽

Fine Print

Object. The mechanisms of brain edema formation following spontaneous intracerebral hemorrhage (ICH) are not well understood. In previous studies, no significant edema formation has been found 24 hours after infusion of packed red blood cells (RBCs) into the brain of a rat or pig; however, there is evidence that hemoglobin can be neurotoxic. In this study, the authors reexamined the role of RBCs and hemoglobin in edema formation after ICH. Methods. The experiments involved infusion of whole blood, packed RBCs, lysed RBCs, rat hemoglobin, or thrombin into the right basal ganglia of Sprague—Dawley rats. The animals were killed at different time points and brain water and ion contents were measured. The results showed that lysed autologous erythrocytes, but not packed erythrocytes, produced marked brain edema 24 hours after infusion and that this edema formation could be mimicked by hemoglobin infusion. Although infusion of packed RBCs did not produce dramatic brain edema during the first 2 days, it did induce a marked increase in brain water content 3 days postinfusion. Edema formation following thrombin infusion peaked at 24 to 48 hours. This is earlier than the peak in edema formation that follows ICH, suggesting that there is a delayed, nonthrombin-mediated, edemogenic component of ICH. Conclusions. These results demonstrate that RBCs play a potentially important role in delayed edema development after ICH and that RBC lysis and hemoglobin toxicity may be useful targets for therapeutic intervention.

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

10.21203/rs.2.13782/v1 ◽

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.

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Intestinal flora imbalance induced by antibiotic use in rats

10.21203/rs.3.rs-25711/v1 ◽

2020 ◽

Author(s):

Guojun Tong ◽

Hai Qian ◽

Dongli Li ◽

Jing Li ◽

Jing Chen ◽

...

Keyword(s):

Intestinal Flora ◽

Antibiotic Use ◽

Female Rats ◽

Average Weight ◽

Sprague Dawley ◽

Reactive Protein ◽

Abdominal Aortic ◽

Tnf Α ◽

Significant Difference ◽

Microbial Analysis

Abstract Background In our study, we administered various concentrations of antibiotics to rats, to investigate the changes in the flora of rat feces. Methods Similar Sprague Dawley female rats (n = 84) were divided into A - G groups. The rat feces were collected for microbial analysis. The analytical method used a different culture medium for bacterial cultures and count colonies under a microscope. On the 11th and 15th days, we dissected one rat in each group, taking 5 ml of abdominal aortic blood. TNF-α, IL1-β, IL-6, and C-reactive protein (CRP) were detected by an enzyme-linked immune sorbent assay (ELISA). Results Rats have an average weight of 176.26 g. Between the groups no significant difference was found for starting average weight (p > 0.05) but after experiments, significant differences existed in weight, food intake, water intake, and stool samples within 2 hours (p = 0.04, 0.016, < 0.001, and 0.009, respectively). Significant differences were found between the groups for nine tested microbiotas (p < 0.001). TNF-α,IL1-β༌IL-6༌and CRP were significantly different between all groups (p < 0.001). Conclusions Antibiotics can cause disorder in rat intestinal flora, also causing an inflammatory response in their blood system.

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Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage

Neurosurgical FOCUS ◽

10.3171/foc.2003.15.4.10 ◽

2003 ◽

Vol 15 (4) ◽

pp. 1-7 ◽

Cited By ~ 19

Author(s):

Takehiro Nakamura ◽

Richard F. Keep ◽

Ya Hua ◽

Timothy Schallert ◽

Julian T. Hoff ◽

...

Keyword(s):

Oxidative Stress ◽

Brain Injury ◽

Intracerebral Hemorrhage ◽

Brain Edema ◽

Iron Chelator ◽

Iron Accumulation ◽

Neurological Deficits ◽

Sprague Dawley ◽

Autologous Whole Blood ◽

The Right

Object In the authors' previous studies they found that brain iron accumulation and oxidative stress contribute to secondary brain damage after intracerebral hemorrhage (ICH). In the present study they investigated whether deferoxamine, an iron chelator, can reduce ICH-induced brain injury. Methods Male Sprague–Dawley rats received an infusion of 100 μl of autologous whole blood into the right basal ganglia and were killed 1, 3, or 7 days thereafter. Iron distribution was examined histochemically (enhanced Perl reaction). The effects of deferoxamine on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Apurinic/apyrimidinic endonuclease/redox effector factor–1 (APE/Ref-1), a repair mechanism for DNA oxidative damage, was quantitated by Western blot analysis. Iron accumulation was observed in the perihematoma zone beginning 1 day after ICH. Deferoxamine attenuated brain edema, neurological deficits, and ICH-induced changes in APE/Ref-1. Conclusions Deferoxamine and other iron chelators may be potential therapeutic agents for treating ICH. They may act by reducing the oxidative stress caused by the release of iron from the hematoma.

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