Abstract WMP24: Quantitative Relaxometry Quantifies Brain Edema After Ischemic Stroke

Introduction: Brain edema is an adverse complication of ischemic stroke, and is associated with substantial morbidity and mortality. We investigated whether relaxometry parameters of MRI are a reliable measure of brain edema in an animal model. Hypothesis: We hypothesize that quantitative relaxometry parameters of MRI in a rat model of stroke tightly correlate with brain edema. Methods: We permanently occluded the middle cerebral artery of 18 rats using the filament occlusion method. Fifteen surviving animals were imaged at 48 hours with a Bruker 4.7 T MRI scanner with Diffusion-weighted imaging (DWI), T1 and T2 maps, and proton-density weighted (PDW) imaging. Hemispheric and lesional volumes were generated on DWI. For quantitative T1, quantitative T2 and PDW images, signal intensity values relative to the contralateral hemisphere were determined. The percent water content in the rat brain was measured using the wet-dry method. Additional volumetric measurements of swelling were calculated based on hemisphere volumes determined on MRI. Correlation testing and logistic regression was performed to assess the relationship between imaging measures and swelling. Results: The mean lesion volume was 352 mm3. Brain water content and swelling volume were closely associated (r=0.80, p<0.001). PDW, T1 and T2 ratios highly correlated with brain water content (r=0.91, p<0.0001, r=0.94, p<0.0001 and r=0.97, p<0.0001, respectively). Ratios for PDW, T1 and T2 were also associated with swelling volume (r=0.67, p<0.0063, r=0.73, p<0.0022, and r=0.74, p<0.0017). Conclusion: Signal intensity ratios derived from PDW as well as quantitative T1 and T2 MRI can be leveraged to quantify brain water content and brain edema. These measures are useful markers for edema quantification that can be applied to any condition that leads to brain edema in both animal models and human patients.

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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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Ulinastatin alleviates traumatic brain injury by reducing endothelin-1

Translational Neuroscience ◽

10.1515/tnsci-2021-0001 ◽

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.

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Abstract WP47: Reperfusion Following Ischemic Stroke is Associated with Reduced Brain Edema

Stroke ◽

10.1161/str.48.suppl_1.wp47 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Hannah J Irvine ◽

Thomas W Battey ◽

Ann-Christin Ostwaldt ◽

Bruce C Campbell ◽

Stephen M Davis ◽

...

Keyword(s):

Ischemic Stroke ◽

Brain Edema ◽

Infarct Volume ◽

Brain Magnetic Resonance Imaging ◽

Lesion Volume ◽

Stroke Patients ◽

Early Reperfusion ◽

Echoplanar Imaging ◽

Swelling Volume

Introduction: Revascularization is a robust therapy for acute ischemic stroke, but animal studies suggest that reperfusion edema may attenuate its beneficial effects. In stroke patients, early reperfusion consistently reduces infarct volume and improves long-term functional outcome, but there is little clinical data available regarding reperfusion edema. We sought to elucidate the relationship between reperfusion and brain edema in a patient cohort of moderate to severe stroke. Methods: Seventy-one patients enrolled in the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) with serial brain magnetic resonance imaging and perfusion-weighted imaging (PWI) were analyzed. Reperfusion percentage was calculated based on the difference in PWI lesion volume at baseline and follow-up (day 3-5). Midline shift (MLS) was measured on the day 3-5 fluid attenuated inversion recovery (FLAIR) sequence. Swelling volume and infarct growth volume were assessed using region-of-interest analysis on the baseline and follow-up DWI scans based on our prior methods. Results: Greater percentage of reperfusion was associated with less MLS (Spearman ρ = -0.46; P <0.0001) and reduced swelling volume (Spearman ρ = -0.56; P <0.0001). In multivariate analysis, reperfusion was an independent predictor of less MLS ( P <0.006) and decreased swelling volume ( P <0.0054), after adjusting for age, baseline NIHSS, admission blood glucose, baseline DWI volume, and IV tPA treatment. Conclusions: Reperfusion is associated with reduced brain edema as measured by MLS and swelling volume. While our data do not exclude the possibility of reperfusion edema in certain circumstances, in stroke patients, reperfusion following acute stroke is predominantly linked to less brain swelling.

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Agmatine Attenuates Brain Edema through Reducing the Expression of Aquaporin-1 after Cerebral Ischemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2009.260 ◽

2009 ◽

Vol 30 (5) ◽

pp. 943-949 ◽

Cited By ~ 37

Author(s):

Jae Hwan Kim ◽

Yong Woo Lee ◽

Kyung Ah Park ◽

Won Taek Lee ◽

Jong Eun Lee

Keyword(s):

Cerebral Ischemia ◽

Water Content ◽

Brain Edema ◽

Arginine Decarboxylase ◽

Artery Occlusion ◽

Brain Swelling ◽

Ischemic Brain ◽

Cerebral Artery Occlusion ◽

Swelling Volume ◽

Brain Water

Brain edema is frequently shown after cerebral ischemia. It is an expansion of brain volume because of increasing water content in brain. It causes to increase mortality after stroke. Agmatine, formed by the decarboxylation of L-arginine by arginine decarboxylase, has been shown to be neuroprotective in trauma and ischemia models. The purpose of this study was to investigate the effect of agmatine for brain edema in ischemic brain damage and to evaluate the expression of aquaporins (AQPs). Results showed that agmatine significantly reduced brain swelling volume 22 h after 2 h middle cerebral artery occlusion in mice. Water content in brain tissue was clearly decreased 24 h after ischemic injury by agmatine treatment. Blood–brain barrier (BBB) disruption was diminished with agmatine than without. The expressions of AQPs-1 and -9 were well correlated with brain edema as water channels, were significantly decreased by agmatine treatment. It can thus be suggested that agmatine could attenuate brain edema by limitting BBB disruption and blocking the accumulation of brain water content through lessening the expression of AQP-1 after cerebral ischemia.

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

Asian Biomedicine ◽

10.5372/1905-7415.0502.026 ◽

2011 ◽

Vol 5 (2) ◽

pp. 205-215 ◽

Cited By ~ 2

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.

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Brain edema after intracerebral hemorrhage in rats: the role of iron overload and aquaporin 4

Journal of Neurosurgery ◽

10.3171/2008.4.jns17512 ◽

2009 ◽

Vol 110 (3) ◽

pp. 462-468 ◽

Cited By ~ 54

Author(s):

Wang Gai Qing ◽

Yang Qi Dong ◽

Tang Qing Ping ◽

Li Guang Lai ◽

Li Dong Fang ◽

...

Keyword(s):

Iron Overload ◽

Water Content ◽

Brain Edema ◽

Time Course ◽

Iron Chelator ◽

Brain Water Content ◽

Edema Formation ◽

Aqp4 Expression ◽

The Right ◽

Brain Water

Object Brain edema formation following intracerebral hemorrhage (ICH) appears to be partly related to erythrocyte lysis and hemoglobin release. An increase of brain water content was associated with an increase of brain iron, which is an erythrocyte degradation product. Expression of AQP4 is highly modified in several brain disorders, and it can play a key role in cerebral edema formation. However, the question whether AQP4 is regulated by drugs lacks reliable evidence, and the interacting roles of iron overload and AQP4 in brain edema after ICH are unknown. The goal of this study was to clarify the relationship between iron overload and AQP4 expression and to characterize the effects of the iron chelator deferoxamine (DFO) on delayed brain edema after experimental ICH. Methods A total of 144 Sprague-Dawley rats weighing between 250 and 300 g were used in this work. The animals were randomly divided into 4 groups. The ICH models (Group C) were generated by injecting 100 μl autologous blood stereotactically into the right caudate nucleus; surgical control rats (Group B) were generated in a similar fashion, by injecting 100 μl saline into the right caudate nucleus. Intervention models (Group D) were established by intraperitoneal injection of DFO into rats in the ICH group. Healthy rats (Group A) were used for normal control models. Brain water content, iron deposition, and AQP4 in perihematomal brain tissue were evaluated over the time course of the study (1, 3, 7, and 14 days) in each group. Results Iron deposition was found in the perihematomal zone as early as the 1st day after ICH, reaching a peak after 7 days and remaining at a high level thereafter for at least 14 days following ICH. Rat brain water content around the hematoma increased progressively over the time course, reached its peak at Day 3, and still was evident at Day 7 post-ICH. Immunohistochemical analysis showed that AQP4 was richly expressed over glial cell processes surrounding microvessels in the rat brain; there was upregulation of the AQP4 expression in perihematomal brain during the observation period, and it reached maximum at 3 to 7 days after ICH. The changes of brain water content were accompanied by an alteration of AQP4. The application of the iron chelator DFO significantly reduced iron overload, brain water content, and AQP4 level in the perihematomal area compared with the control group. Conclusions Iron overload and AQP4 may play a critical role in the formation of brain edema after ICH. In addition, AQP4 expression was affected by iron concentration. Importantly, treatment with DFO significantly reduced brain edema in rats and inhibited the AQP4 upregulation after ICH. Deferoxamine may be a potential therapeutic agent for treating ICH.

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Microvascular Changes during the Early Phase of Experimental Bacterial Meningitis

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1990.148 ◽

1990 ◽

Vol 10 (6) ◽

pp. 914-922 ◽

Cited By ~ 94

Author(s):

H.-W. Pfister ◽

U. Koedel ◽

R. L. Haberl ◽

U. Dirnagl ◽

W. Feiden ◽

...

Keyword(s):

Free Radicals ◽

Bacterial Meningitis ◽

Water Content ◽

Brain Edema ◽

Early Phase ◽

Brain Water Content ◽

Edema Formation ◽

Oxygen Derived Free Radicals ◽

Brain Water ◽

Brain Edema Formation

We investigated the temporal profile of the changes in regional CBF (rCBF) and intracranial pressure (ICP) during the early phase of pneumococcal meningitis in the rat. rCBF, as measured by laser-Doppler flowmetry, and ICP were continuously monitored during 6 h post infection (p.i.). Brain edema formation was assessed by brain water content determinations. Meningitis was induced by intracisternal injection of 75 μl of 107 colony-forming units/ml pneumococci (n = 7). In control animals (n = 6), saline was injected. There was no change in the rCBF or ICP of controls throughout the experiment. However, there was a dramatic increase in rCBF and ICP associated with brain edema formation in untreated meningitis animals. rCBF increased to 135.3 ± 33.8% (mean ± SD) in the untreated animals at 1 h p.i, and reached 211.1 ± 40.5% at 6 h p.i. (p < 0.05 compared with controls). ICP increased from 2.9 ± 1.4 to 10.4 ± 4.7 mm Hg at 6 h p.i. (p < 0.05 compared with controls). Brain water content was significantly elevated (79.69 ± 0.24 compared with 78.94 ± 0.16% in the control group, p < 0.05). We investigated the effect of dexamethasone (3 mg/kg i.p.), which was given prior to the induction of meningitis (n = 3) or at 2 h after pneumococcal injection (n = 5), indomethacin (10 mg/kg i.V., n = 5), and superoxide dismutase (SOD; 132,000 U/kg i.v. per 6 h, n = 6). The increases in rCBF and ICP were prevented by the pretreatment with dexamethasone and the administration of SOD, delayed and attenuated by pretreatment with indomethacin, and reversed by administration of dexamethasone 2 h p.i. These findings suggest that oxygen-derived free radicals are involved as mediators in the increases of rCBF and ICP and brain edema formation during the early phase of experimental bacterial meningitis. Arachidonic acid metabolites of the cyclooxygenase pathway are partially involved in the observed changes and are one possible source for the generation of oxygen-derived free radicals in bacterial meningitis.

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Brain edema formation and neurological impairment after subarachnoid hemorrhage in rats

Journal of Neurosurgery ◽

10.3171/2009.3.jns08412 ◽

2009 ◽

Vol 111 (5) ◽

pp. 988-994 ◽

Cited By ~ 31

Author(s):

Serge C. Thal ◽

Sonja Sporer ◽

Mariusz Klopotowski ◽

Simone E. Thal ◽

Johannes Woitzik ◽

...

Keyword(s):

Water Content ◽

Brain Edema ◽

Neuronal Cell ◽

Cell Loss ◽

Neurological Deficits ◽

Brain Water Content ◽

Edema Formation ◽

Neuronal Cell Loss ◽

Brain Water ◽

Brain Edema Formation

Object Global cerebral edema is an independent risk factor for early death and poor outcome after subarachnoid hemorrhage (SAH). In the present study, the time course of brain edema formation, neurological deficits, and neuronal cell loss were investigated in the rat filament SAH model. Methods Brain water content and neurological deficits were determined in rats randomized to sham (1-, 24-, or 48-hour survival), SAH by endovascular perforation (1-, 24-, or 48-hour survival), or no surgery (control). The neuronal cell count (CA1–3) was quantified in a separate set of SAH (6-, 24-, 48-, or 72-hour survival) and shamoperated animals. Results Brain water content increased significantly 24 (80.2 ± 0.4% [SAH] vs 79.2 ± 0.1% [sham]) and 48 hours (79.8 ± 0.2% [SAH] vs 79.3 ± 0.1% [sham]) after SAH. The neuroscore was significantly worse after SAH (33 ± 15 [24 hours after SAH] vs 0 ± 0 points [sham]) and correlated with the extent of brain edema formation (r = 0.96, p < 0.001). No hippocampal damage was present up to 72 hours after SAH. Conclusions Brain water content and neurological dysfunction reached a maximum at 24 hours after SAH. This time point, therefore, seems to be optimal to test the effects of therapeutic interventions on brain edema formation. Neuronal cell loss was not present in CA1–3 up to 72 hours of SAH. Therefore, morphological damage needs to be evaluated at later time points.

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Neuroprotection of Sanhua Decoction against Focal Cerebral Ischemia/Reperfusion Injury in Rats through a Mechanism Targeting Aquaporin 4

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/584245 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Lin Lu ◽

Hui-qin Li ◽

Ji-huang Li ◽

Ai-ju Liu ◽

Guo-qing Zheng

Keyword(s):

Cerebral Ischemia ◽

Water Content ◽

Brain Edema ◽

Focal Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Aquaporin 4 ◽

Brain Water Content ◽

Aqp4 Expression ◽

Cerebral Ischemia Reperfusion ◽

Brain Water

Sanhua decoction (SHD) is a famous classic Chinese herbal prescription for ischemic stroke, and aquaporin 4 (AQP4) is reported to play a key role in ischemic brain edema. This study aimed to investigate neuroprotection of SHD against focal cerebral ischemia/reperfusion (I/R) injury in rats and explore the hypothesis that AQP4 probably is the target of SHD neuroprotection against I/R rats. Lentiviral-mediated AQP4-siRNA was inducted into adult male Sprague-Dawley rats via intracerebroventricular injection. The focal cerebral ischemia/reperfusion model was established by occluding middle cerebral artery. Neurological examinations were performed according to Longa Scale. Brain water content, was determined by wet and dry weight measurement. Western blot was adopted to test the AQP4 expression in ipsilateral hippocampus. After the treatment, SHD alleviated neurological deficits, reduced brain water content and downregulated the expression of AQP4 at different time points following I/R injury. Furthermore, neurobehavioral function and brain edema after I/R were significantly attenuated via downregulation of AQP4 expression when combined with AQP4-siRNA technology. In conclusion, SHD exerted neuroprotection against focal cerebral I/R injury in rats mainly through a mechanism targeting AQP4.

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Hydrochloride fasudil attenuates brain injury in ICH rats

Translational Neuroscience ◽

10.1515/tnsci-2020-0100 ◽

2020 ◽

Vol 11 (1) ◽

pp. 75-86

Author(s):

Limin Li ◽

Xiaoli Lou ◽

Kunlun Zhang ◽

Fangping Yu ◽

Yingchun Zhao ◽

...

Keyword(s):

Water Content ◽

Brain Edema ◽

Inflammatory Cytokines ◽

Neuronal Morphology ◽

Enzyme Linked Immunosorbent Assay ◽

Brain Water Content ◽

Nissl Staining ◽

Neuroprotective Effects ◽

Arterial Blood ◽

Brain Water

AbstractAimThe aim of this study was to investigate the neuroprotective effects of hydrochloride fasudil (HF) in rats following intracerebral hemorrhage (ICH).MethodsMale Wistar rats were randomly divided into four groups: normal, sham-operated, ICH, and ICH/HF. ICH was induced by injection of non-anticoagulant autologous arterial blood into the right caudate nucleus. The levels of Rho-associated protein kinase 2 (ROCK2) mRNA and protein around the site of the hematoma were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. The levels of interleukin-6 and tumor necrosis factor-α in serum were detected by ELISA. The inflammatory cells and changes in the neuronal morphology around the hematoma were visualized using hematoxylin and eosin and Nissl staining. Brain edema was measured by comparing wet and dry brain weights.ResultsFollowing ICH, the levels of ROCK2 were significantly increased from day 1 to day 7. The levels of ROCK2 were significantly lower in rats treated with HF than in controls. The levels of inflammatory cytokines and brain water content were significantly higher in rats treated with HF than in controls. Administration of HF significantly reduced the levels of inflammatory cytokines and brain water content from day 1 to day 7. In the acute phase of ICH, a large number of neutrophils infiltrated the perihematomal areas. In comparison with the ICH group, the ICH/HF group showed markedly fewer infiltrating neutrophils on day 1. Nissl staining showed that ICH caused neuronal death and loss of neurons in the perihematomal areas at all time points and that treatment with HF significantly attenuated neuronal loss.ConclusionsHF exerts neuroprotective effects in ICH rats by inhibiting the expression of ROCK2, reducing neutrophil infiltration and production of inflammatory cytokines, decreasing brain edema, and attenuating loss of neurons.

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