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Julian T. Hoff - One of the best experts on this subject based on the ideXlab platform.
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overexpression of interleukin 1 receptor antagonist reduces Brain Edema induced by intracerebral hemorrhage and thrombin
Acta Neurochirurgica, 2003Co-Authors: Tetsuya Masada, Richard F. Keep, Julian T. Hoff, Guoyuan Yang, Ya Hua, Seigo NagaoAbstract:Recent studies indicate that inflammatory reaction occurs around hematoma after intracerebral hemorrhage (ICH). In this study the authors examine the hypothesis that overexpression of IL-1ra in the Brain attenuate Brain Edema formation after ICH .
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pathophysiology of Brain Edema formation
Neurosurgery Clinics of North America, 2002Co-Authors: Richard F. Keep, Julian T. HoffAbstract:A number of mechanisms seem to be involved in Edema formation after an ICH. At least three phases of Edema are involved in ICH. These include a very early phase (first several hours) involving hydrostatic pressure and clot retraction, a second phase (first 2 days) involving the activation of the coagulation cascade and thrombin production, and a third phase (after 3 days) involving RBC lysis and hemoglobin-induced neuronal toxicity. Activation of the complement system in Brain parenchyma also plays an important role in the second and third phases. There are potential therapeutic strategies to address each of these mechanisms. Because the adverse effect of an ICH seems to result from a toxic effect of blood components on Brain tissue, early clot removal may be the best strategy, because it results in the removal of all the toxic components [93]. Hematoma aspiration after tissue plasminogen activator (tPA) infusion has also been shown to be relatively safe and effective in animal models. Kaufman et al [94] reported that tPA lysed the hematoma in minutes and did not cause inflammation or bleeding in rabbits. Because clots lysed with tPA can be aspirated through a needle or catheter, mechanical Brain injury by this method is minimized. In a rat model, aspiration of clot with tPA reduced clot volume and Brain injury [95,96]. Recently, Wagner et al [97] infused tPA into hematomas in a porcine model at 3 hours after induction and aspirated the liquified clots 1 hour later. Clot removal after tPA treatment resulted in a 72% reduction in hematoma volume compared with untreated controls. Clot removal also reduced Brain Edema volume and BBB disruption and improved cerebral tissue pressure [93]. Six randomized trials have been accomplished, but surgical evacuation of the clot remains controversial [98-103]. Recently, thrombolysis and aspiration under CT guidance reduced the hematoma volume effectively [104]. Infusion of tPA directly into the hematoma before clot aspiration has also been used in human beings. Up to 90% of the original hematoma volume can be removed [105, 106]. Schaller et al [107] injected tPA directly into a hematoma 72 hours after the ictus in patients. The hematomas were lysed, and the liquified clots were drained in 14 patients. Two patients died, but none had recurrent hemorrhage. In conclusion, much has been learned about the basic mechanisms involved in Edema formation after ICH. Animal models indicate that a number of components of blood are capable of inducing Brain injury and Brain Edema. Now, it is time to translate that basic information into clinical trials.
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Brain Edema after experimental intracerebral hemorrhage role of hemoglobin degradation products
Journal of Neurosurgery, 2002Co-Authors: Feng Ping Huang, Richard F. Keep, Guohua Xi, Andrei Nemoianu, Julian T. HoffAbstract:Object. The mechanisms involved in Brain Edema formation following intracerebral hemorrhage (ICH) have not been fully elucidated. The authors have found that red blood cell lysis plays an important role in Edema development after ICH. In the present study, they sought to determine whether degradation products of hemoglobin cause Brain Edema. Methods. Hemoglobin, hemin, bilirubin, or FeCl2 were infused with stereotactic guidance into the right basal ganglia of Sprague—Dawley rats. The animals were killed 24 hours later to determine Brain water and ion contents. Western blot analysis and immunohistochemistry were applied for heme oxygenase-1 (HO-1) measurement. The effects of an HO inhibitor, tin-protoporphyrin (SnPP), and the iron chelator deferoxamine, on hemoglobin-induced Brain Edema were also examined. Intracerebral infusion of hemoglobin, hemin, bilirubin, or FeCl2 caused an increase in Brain water content at 24 hours. The HO-1 was upregulated after hemoglobin infusion and HO inhibition by SnPP-attenu...
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erythrocytes and delayed Brain Edema formation following intracerebral hemorrhage in rats
Journal of Neurosurgery, 1998Co-Authors: Guohua Xi, Richard F. Keep, Julian T. HoffAbstract: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 indu...
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The role of the coagulation cascade in Brain Edema formation after intracerebral hemorrhage.
Acta Neurochirurgica, 1996Co-Authors: Ko Lee, A. L. Betz, Seoung Kim, Richard F. Keep, Julian T. HoffAbstract:The coagulation cascade has a potential role in Brain Edema formation due to intracerebral hemorrhage. In this study blood and other solutions were injected stereotactically into the right basal ganglia in rats. Twenty-four hours following injection, Brain water and ion contents were measured to determine the amount of Brain Edema. Intracerebral blood resulted in an increase in Brain water content. The amount of Brain Edema surrounding the intracerebral hematoma was reduced by a thrombin inhibitor Na-(2-Naphthalenesulfonylglycyl)-4-amidino-DL-phenylalaninepiperidide, (α-NAPAP) infused into the hematoma after the clot had been allowed to solidify. The inhibitor did not alter the actual size of the clot mass. An artificial clot composed of fibrinogen, thrombin, and styrene microspheres also produced Brain Edema. A fibrin clot led to Edema formation even in the absence of mass effect provided by the microspheres. The single component responsible for production of Brain Edema in all these models was thrombin. The Edema was formed in response to a fibrinogen-independent pathway. These results indicate that the coagulation cascade is involved in Brain Edema that develops adjacent to an intracerebral hematoma.
Seigo Nagao - One of the best experts on this subject based on the ideXlab platform.
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expression of matrix metalloproteinse 9 in thrombin induced Brain Edema formation in rats
Journal of Stroke & Cerebrovascular Diseases, 2006Co-Authors: Kenya Kawakita, Nobuyuki Kawai, Yasuhiro Kuroda, Susumu Yasashita, Seigo NagaoAbstract:Recent evidence has demonstrated that thrombin plays an important role in the development of Brain Edema by the blood-Brain barrier disruption in intracerebral hemorrhage. Matrix metalloproteinases (MMPs), a family of proteolytic enzymes that degrade the extracellular matrix, are implicated in blood-Brain barrier disruption. In this study, we examined whether thrombin injection into the Brain parenchyma induces the MMP-9 expression in rats. Anesthetized adult rats received an injection of 10 U of thrombin into the basal ganglia. At 12, 24, and 72 hours after the thrombin injection, Brain water content and the expression of MMP-9 messenger RNA (mRNA) and protein were determined. The effect of a specific thrombin inhibitor (hirudin) on MMP-9 expression and Brain Edema formation and general administration of synthetic MMPs inhibitor (GM6001) on Brain Edema formation were also examined for linking the injury and up-regulation of MMP-9. The Brain water contents in the basal ganglia and overlying cortex were rapidly increased at 12 hours, maximized at 24 hours, and slightly decreased at 72 hours. The gelatinase activity of MMP-9 determined with gelatin zymography was detected in the basal ganglia and cortex at 12 hours, maximally expressed at 24 hours, and remained strong 72 hours after thrombin injection. The expression of MMP-9 mRNA in the cortex determined with reverse transcription-polymerase chain reaction was clearly seen at 12 and 24 hours, and became weak 72 hours after thrombin injection. Co-injection of thrombin and hirudin almost completely inhibited the Brain Edema formation and expressions of MMP-9 mRNA and protein. Administration of broad-spectrum metalloproteinase inhibitor GM6001 significantly reduced the Brain Edema formation in this model. These results indicate that intraparenchymal thrombin induces Brain Edema formation through MMP-9 expression in rats. Inhibition of MMPs activity may provide an approach to potentially reduce ongoing Edema after intracerebral hemorrhage.
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overexpression of interleukin 1 receptor antagonist reduces Brain Edema induced by intracerebral hemorrhage and thrombin
Acta Neurochirurgica, 2003Co-Authors: Tetsuya Masada, Richard F. Keep, Julian T. Hoff, Guoyuan Yang, Ya Hua, Seigo NagaoAbstract:Recent studies indicate that inflammatory reaction occurs around hematoma after intracerebral hemorrhage (ICH). In this study the authors examine the hypothesis that overexpression of IL-1ra in the Brain attenuate Brain Edema formation after ICH .
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effects of hypothermia on thrombin induced Brain Edema formation
Brain Research, 2001Co-Authors: Nobuyuki Kawai, Masahiko Kawanishi, Masanobu Okauchi, Seigo NagaoAbstract:Abstract Recent studies have shown that thrombin plays an important role in Brain Edema formation after intracerebral hemorrhage (ICH). The possible mechanisms of thrombin-induced Brain Edema formation include blood–Brain barrier (BBB) disruption and inflammatory response involving polymorphonuclear (PMN) leukocyte. Animal experiments have revealed that moderate therapeutic hypothermia improves pathological and functional outcome in various models of Brain injury. In this study, we examined the effect of hypothermia on thrombin-induced Brain Edema formation. Effects of hypothermia on BBB permeability and the accumulation of PMN leukocytes were also determined to clarify the protective mechanism of hypothermia in this model. Anesthetized adult rats received an injection of 10 Units of thrombin into the basal ganglia. Animals were separated into the normothermic and hypothermic groups, which were housed in a room maintained at 25°C and in a cold room maintained at 5°C, respectively, for 24 h after the thrombin injection. The Brain temperature in rats housed in a cold room reduced temporarily to approximately 30°C and then gradually recovered to 35°C by the end of the observation. Brain water content in the basal ganglia was significantly reduced in rats treated with hypothermia compared to the normothermic rats (84.3±0.2 vs. 82.4±0.1%; P
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effects of hypothermia on intracranial pressure and Brain Edema formation studies in a rat acute subdural hematoma model
Journal of Neurotrauma, 2000Co-Authors: Nobuyuki Kawai, Masanobu Okauchi, Takehiro Nakamura, Seigo NagaoAbstract:Acute subdural hematoma (SDH) is the most common mass lesion in severe head injury, and Brain ischemia is the leading pathophysiological mechanism in the development of secondary Brain damage following SDH. Hypothermia has been employed as an effective neuroprotective procedure in clinical and laboratory studies on cerebral ischemic and contusional injuries. In the present study, we used a rat acute SDH model to assess the effect of hypothermia on the intracranial pressure (ICP) and also on the Brain Edema formation at 4 h after hematoma induction. Mild (34 degrees C) and moderate (32 degrees C) hypothermia did not significantly affect the ICP or cerebral perfusion pressure, but they were associated with a significant lower cortical Brain Edema formation beneath the hematoma (81.09 +/- 0.49%, p<0.05; and 80.88 +/- 0.17%, p<0.01) when compared with the normothermic control group (81.65 +/- 0.52%). This reduction in Brain Edema formation was comparable to the results of MK-801 treatment (80.95 +/- 0.35%, p<0.01). The present findings indicate that hypothermia represents a potent neuroprotective strategy. The possible protective mechanisms of hypothermic protection afforded in this rat acute SDH model are discussed.
Jun Guo - One of the best experts on this subject based on the ideXlab platform.
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intracellular ion and protein nanoparticle induced osmotic pressure modify astrocyte swelling and Brain Edema in response to glutamate stimuli
Redox biology, 2019Co-Authors: Jiarui Zhang, Yuxuan Wang, Zihui Zheng, Xiaohe Sun, Tingting Chen, Xiaolong Zhang, Jun GuoAbstract:Abstract Intracellular tension activity plays a crucial role in cytotoxic Brain Edema and astrocyte swelling. Here, a few genetically encoded FRET-based tension probes were designed to detect cytoskeletal structural tension optically, including their magnitude and vectors. The astrocyte swelling resulted in GFAP tension increment, which is associated with the antagonistic effect of inward microfilaments (MFs) and microtubules (MTs) forces. In glutamate-induced astrocyte swelling, GFAP tension rise resulted from outward ion and protein nanoparticle-induced osmotic pressure (PN-OP) increases, where PN-OP could be elicited by MF and MT depolymerization, protein nanoparticle production, and activation of cofilin and stathmin-1. Attenuation of both ion osmotic pressure and PN-OP by drug combinations, together with free-radical scavenger, relieved cerebral Edema in vivo. The study suggests that intracellular osmotic pressure (especially PN-OP) has a pivotal role in glutamate-induced astrocyte swelling and Brain Edema. Recovery of cytoplasmic potential is a promising target to develop new drugs and cure Brain Edema.
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Intracellular ion and protein nanoparticle-induced osmotic pressure modify astrocyte swelling and Brain Edema in response to glutamate stimuli
Elsevier, 2019Co-Authors: Jiarui Zhang, Yuxuan Wang, Zihui Zheng, Xiaohe Sun, Tingting Chen, Xiaolong Zhang, Jun GuoAbstract:Intracellular tension activity plays a crucial role in cytotoxic Brain Edema and astrocyte swelling. Here, a few genetically encoded FRET-based tension probes were designed to detect cytoskeletal structural tension optically, including their magnitude and vectors. The astrocyte swelling resulted in GFAP tension increment, which is associated with the antagonistic effect of inward microfilaments (MFs) and microtubules (MTs) forces. In glutamate-induced astrocyte swelling, GFAP tension rise resulted from outward ion and protein nanoparticle-induced osmotic pressure (PN-OP) increases, where PN-OP could be elicited by MF and MT depolymerization, protein nanoparticle production, and activation of cofilin and stathmin-1. Attenuation of both ion osmotic pressure and PN-OP by drug combinations, together with free-radical scavenger, relieved cerebral Edema in vivo. The study suggests that intracellular osmotic pressure (especially PN-OP) has a pivotal role in glutamate-induced astrocyte swelling and Brain Edema. Recovery of cytoplasmic potential is a promising target to develop new drugs and cure Brain Edema. Keywords: Brain Edema, Astrocyte, Glutamate, Protein nanoparticle-induced osmotic pressure, GFAP tension prob
M. D. Norenberg - One of the best experts on this subject based on the ideXlab platform.
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Sulfonylurea Receptor 1 Contributes to the Astrocyte Swelling and Brain Edema in Acute Liver Failure
Translational Stroke Research, 2014Co-Authors: A. R. Jayakumar, V. Valdes, X. Y. Tong, N. Shamaladevi, W. Gonzalez, M. D. NorenbergAbstract:Astrocyte swelling (cytotoxic Brain Edema) is the major neurological complication of acute liver failure (ALF), a condition in which ammonia has been strongly implicated in its etiology. Ion channels and transporters are known to be involved in cell volume regulation, and a disturbance in these systems may result in cell swelling. One ion channel known to contribute to astrocyte swelling/Brain Edema in other neurological disorders is the ATP-dependent, nonselective cation (NCCa-ATP) channel. We therefore examined its potential role in the astrocyte swelling/Brain Edema associated with ALF. Cultured astrocytes treated with 5 mM ammonia showed a threefold increase in the sulfonylurea receptor type 1 (SUR1) protein expression, a marker of NCCa-ATP channel activity. Blocking SUR1 with glibenclamide significantly reduced the ammonia-induced cell swelling in cultured astrocytes. Additionally, overexpression of SUR1 in ammonia-treated cultured astrocytes was significantly reduced by cotreatment of cells with BAY 11–7082, an inhibitor of NF-κB, indicating the involvement of an NF-κB-mediated SUR1 upregulation in the mechanism of ammonia-induced astrocyte swelling. Brain SUR1 mRNA level was also found to be increased in the thioacetamide (TAA) rat model of ALF. Additionally, we found a significant increase in SUR1 protein expression in rat Brain cortical astrocytes in TAA-treated rats. Treatment with glibenclamide significantly reduced the Brain Edema in this model of ALF. These findings strongly suggest the involvement of NCCa-ATP channel in the astrocyte swelling/Brain Edema in ALF and that targeting this channel may represent a useful approach for the treatment of the Brain Edema associated with ALF.
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Brain Edema in acute liver failure inhibition by l histidine
American Journal of Pathology, 2010Co-Authors: Kakulavarapu Rama V Rao, M. D. Norenberg, Pichili V B Reddy, Xiaoying TongAbstract:Brain Edema and the associated increase in intracranial pressure are potentially lethal complications of acute liver failure (ALF). Astrocyte swelling (cytotoxic Edema) represents a significant component of the Brain Edema in ALF, and elevated blood and Brain ammonia levels have been strongly implicated in its formation. We earlier showed in cultured astrocytes that oxidative stress (OS) and the mitochondrial permeability transition (mPT) play major roles in the mechanism of ammonia-induced astrocyte swelling. Glutamine, a byproduct of ammonia metabolism, has also been shown to induce OS, the mPT, and astrocyte swelling. Such effects of glutamine were suggested to be mediated by its hydrolysis in mitochondria, potentially yielding high levels of ammonia in this organelle and leading to OS and the mPT. L-histidine, an inhibitor of mitochondrial glutamine transport, was recently shown to mitigate OS, mPT, and cell swelling in cultured astrocytes treated with ammonia. The present study examined whether L-histidine similarly abolishes OS, the mPT, and Brain Edema in a rat model of ALF. Treatment of rats with thioacetamide caused a significant degree of Brain Edema, which was associated with induction of OS and the mPT. These changes were completely abolished by L-histidine, supporting a key role of mitochondrial glutamine transport and hydrolysis in the mechanism of the Brain Edema associated with ALF.
Christopher F Rose - One of the best experts on this subject based on the ideXlab platform.
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increased Brain lactate is central to the development of Brain Edema in rats with chronic liver disease
Journal of Hepatology, 2014Co-Authors: Cristina R Bosoi, Claudia Zwingmann, Helen A Marin, Christian Parentrobitaille, Jimmy Huynh, Melanie Tremblay, Christopher F RoseAbstract:Background & Aims The pathogenesis of Brain Edema in patients with chronic liver disease (CLD) and minimal hepatic encephalopathy (HE) remains undefined. This study evaluated the role of Brain lactate, glutamine and organic osmolytes, including myo-inositol and taurine, in the development of Brain Edema in a rat model of cirrhosis. Methods Six-week bile-duct ligated (BDL) rats were injected with 13 C-glucose and de novo synthesis of lactate, and glutamine in the Brain was quantified using 13 C nuclear magnetic resonance spectroscopy (NMR). Total Brain lactate, glutamine, and osmolytes were measured using 1 H NMR or high performance liquid chromatography. To further define the interplay between lactate, glutamine and Brain Edema, BDL rats were treated with AST-120 (engineered activated carbon microspheres) and dichloroacetate (DCA: lactate synthesis inhibitor). Results Significant increases in de novo synthesis of lactate (1.6-fold, p p vs. SHAM-operated controls. Moreover, a decrease in cerebral myo-inositol ( p vs. controls. BDL rats treated with either AST-120 or DCA showed attenuation in Brain Edema and Brain lactate. These two treatments did not lead to similar reductions in Brain glutamine. Conclusions Increased Brain lactate, and not glutamine, is a primary player in the pathogenesis of Brain Edema in CLD. In addition, alterations in the osmoregulatory response may also be contributing factors. Our results suggest that inhibiting lactate synthesis is a new potential target for the treatment of HE.
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Brain Edema in acute liver failure and chronic liver disease similarities and differences
Neurochemistry International, 2013Co-Authors: Cristina R Bosoi, Christopher F RoseAbstract:Abstract Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that typically develops as a result of acute liver failure or chronic liver disease. Brain Edema is a common feature associated with HE. In acute liver failure, Brain Edema contributes to an increase in intracranial pressure, which can fatally lead to Brain stem herniation. In chronic liver disease, intracranial hypertension is rarely observed, even though Brain Edema may be present. This discrepancy in the development of intracranial hypertension in acute liver failure versus chronic liver disease suggests that Brain Edema plays a different role in relation to the onset of HE. Furthermore, the pathophysiological mechanisms involved in the development of Brain Edema in acute liver failure and chronic liver disease are dissimilar. This review explores the types of Brain Edema, the cells, and pathogenic factors involved in its development, while emphasizing the differences in acute liver failure versus chronic liver disease. The implications of Brain Edema developing as a neuropathological consequence of HE, or as a cause of HE, are also discussed.