Intracerebral infusion of thrombin as a cause of brain edema

1995 ◽  
Vol 83 (6) ◽  
pp. 1045-1050 ◽  
Author(s):  
Kevin R. Lee ◽  
A. Lorris Betz ◽  
Richard F. Keep ◽  
Thomas L. Chenevert ◽  
Seoung Kim ◽  
...  
Keyword(s):  
Brain Edema ◽  
Brain Parenchyma ◽  
Thrombin Inhibitor ◽  
Neurosurgical Procedures ◽  
Edema Formation ◽  
Content Type ◽  
The Right ◽  
The Brain ◽  
Brain Water ◽  
Fine Print

✓ Purified thrombin from an exogenous source is a hemostatic agent commonly used in neurosurgical procedures. The toxicity of thrombin in the brain, however, has not been examined. This study was performed to assess the effect of thrombin on brain parenchyma, using the formation of brain edema as an indicator of injury. Ten µl of test solution was infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later, and the extent of brain edema and ion content were measured. Concentrations of human thrombin as low as 1 U/µl resulted in a significant increase in brain water content. Rats receiving 10 U/µl had a mortality rate of 33% compared to no mortality in the groups receiving smaller doses. Thrombin-induced brain edema was inhibited by a specific and potent thrombin inhibitor, hirudin. A medical grade of bovine thrombin commonly used in surgery also caused brain edema when injected at a concentration of 2 U/µl. Edema formation was prevented by another highly specific thrombin inhibitor, Nα-(2-Naphthalenesulfonylglycyl)-4-dl-phenylalaninepiperidide (α-NAPAP). Thrombininduced brain edema was accompanied by increases in brain sodium and chloride contents and a decrease in brain potassium content. Changes in brain ions were inhibited by both hirudin and α-NAPAP, corresponding to the inhibition of brain water accumulation. This study shows that thrombin causes brain edema when infused into the brain at concentrations as low as 1 U/µl, an amount within the range of concentrations used for topical hemostasis in neurosurgery.

Complement activation in the brain after experimental intracerebral hemorrhage

2000 ◽  
Vol 92 (6) ◽  
pp. 1016-1022 ◽  
Author(s):  
Ya Hua ◽  
Guohua Xi ◽  
Richard F. Keep ◽  
Julian T. Hoff
Keyword(s):  
Brain Edema ◽  
Complement Activation ◽  
Autologous Blood ◽  
Complement Cascade ◽  
Edema Formation ◽  
Content Type ◽  
Erythrocyte Lysis ◽  
The Brain ◽  
Brain Edema Formation ◽  
Fine Print

Object. Brain edema formation following intracerebral hemorrhage (ICH) appears to be partly related to erythrocyte lysis and hemoglobin release. Erythrocyte lysis may be mediated by the complement cascade, which then triggers parenchymal injury. In this study the authors examine whether the complement cascade is activated after ICH and whether inhibition of complement attenuates brain edema around the hematoma.Methods. This study was divided into three parts. In the first part, 100 µl of autologous blood was infused into the rats' right basal ganglia, and the animals were killed at 24 and 72 hours after intracerebral infusion. Their brains were tested for complement factors C9, C3d, and clusterin (a naturally occurring complement inhibitor) by using immunohistochemical analysis. In the second part of the study, the rats were killed at 24 or 72 hours after injection of 100 µl of blood. The C9 and clusterin proteins were quantitated using Western blot analysis. In the third part, the rats received either 100 µl of blood or 100 µl of blood plus 10 µg of N-acetylheparin (a complement activation inhibitor). Then they were killed 24 or 72 hours later for measurement of brain water and ion contents. It was demonstrated on Western blot analysis that there had been a sixfold increase in C9 around the hematoma 24 hours after the infusion of 100 µl of autologous blood. Marked perihematomal C9 immunoreactivity was detected at 72 hours. Clusterin also increased after ICH and was expressed in neurons 72 hours later. The addition of N-acetylheparin significantly reduced brain edema formation in the ipsilateral basal ganglia at 24 hours (78.5 ± 0.5% compared with 81.6 ± 0.8% in control animals, p < 0.001) and at 72 hours (80.9 ± 2.2% compared with 83.6 ± 0.9% in control animals, p < 0.05) after ICH.Conclusions. It was found that ICH causes complement activation in the brain. Activation of complement and the formation of membrane attack complex contributes to brain edema formation after ICH. Blocking the complement cascade could be an important step in the therapy for ICH.

Edema from intracerebral hemorrhage: the role of thrombin

1996 ◽  
Vol 84 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Kevin R. Lee ◽  
Gary P. Colon ◽  
A. Lorris Betz ◽  
Richard F. Keep ◽  
Seoung Kim ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Whole Blood ◽  
Blood Clot ◽  
Coagulation Cascade ◽  
Thrombin Inhibitor ◽  
Edema Formation ◽  
Content Type ◽  
Ion Contents ◽  
The Right

✓ The mechanism by which intracerebral hemorrhage leads to the formation of brain edema is unknown. This study assesses the components of blood to determine if any are toxic to surrounding brain. Various solutions were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; brain edema and ion contents were measured. Whole blood caused an increase in brain water content and ion changes consistent with brain edema. Concentrated blood cells, serum from clotted blood, and plasma from unclotted blood all failed to provoke edema formation when infused directly into the brain. On the other hand, activation of the coagulation cascade by adding prothrombinase to plasma did produce brain edema. The edema response to whole blood could be prevented by adding a specific thrombin inhibitor, hirudin, to the injected blood. This study indicates that thrombin plays an important role in edema formation from an intracerebral blood clot.

Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats

1998 ◽  
Vol 89 (6) ◽  
pp. 991-996 ◽  
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.

Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products

2002 ◽  
Vol 96 (2) ◽  
pp. 287-293 ◽  
Author(s):  
Feng-Ping Huang ◽  
Guohua Xi ◽  
Richard F. Keep ◽  
Ya Hua ◽  
Andrei Nemoianu ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Degradation Products ◽  
Heme Oxygenase 1 ◽  
Sprague Dawley ◽  
Edema Formation ◽  
Content Type ◽  
Hemoglobin Degradation ◽  
Brain Water ◽  
Fine Print

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-attenuated hemoglobin-induced edema. Brain edema induced by hemoglobin was also attenuated by the intraperitoneal injection of 500 mg/kg deferoxamine. Conclusions. Hemoglobin causes brain edema, at least in part, through its degradation products. Limiting hemoglobin degradation coupled with the use of iron chelators may be a novel therapeutic approach to limit brain edema after ICH.

scholarly journals Ulinastatin alleviates traumatic brain injury by reducing endothelin-1

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.

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

2009 ◽  
Vol 110 (3) ◽  
pp. 462-468 ◽  
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.

A transparent sheath for endoscopic surgery and its application in surgical evacuation of spontaneous intracerebral hematomas

2000 ◽  
Vol 92 (6) ◽  
pp. 1053-1055 ◽  
Author(s):  
Tetsuhiro Nishihara ◽  
Akira Teraoka ◽  
Akio Morita ◽  
Keisuke Ueki ◽  
Keisuke Takai ◽  
...  
Keyword(s):  
Endoscopic Surgery ◽  
Brain Parenchyma ◽  
Bleeding Point ◽  
Content Type ◽  
Minimal Invasiveness ◽  
Surgical Evacuation ◽  
Endoscopic Evacuation ◽  
Surgical Field ◽  
The Brain ◽  
Fine Print

✓ The authors advocate the use of a transparent sheath for guiding an endoscope, a simple and unique tool for endoscopic surgery, and describe preliminary results of its application in the evacuation of hypertensive intracerebral hematomas. This sheath is a 10-cm-long tube made of clear acrylic plastic, which greatly improves visualization of the surgical field through a 2.7-mm nonangled endoscope inserted within. Between April 1997 and December 1998, the authors performed endoscopic evacuation of intracerebral hematomas by using this sheath inserted into the patients' heads through a burr hole. In nine consecutive cases in which the hematoma was larger than 40 ml in volume, nearly complete evacuation (86–100%) of the lesion was achieved without complication. Excellent visualization of the border between the brain parenchyma and the hematoma facilitated accurate intraoperative orientation, and also allowed easy identification of the bleeding point. Thus, this combination of sheath and endoscope achieves both minimal invasiveness and the maximum extent of hematoma removal with secure hemostasis. This tool will reduce the inherent disadvantage of endoscopic procedures and may expand their application in other areas of neurosurgical management.

Composition of isolated edema fluid in cold-induced brain edema

1979 ◽  
Vol 51 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Jurjen Gazendam ◽  
K. Gwan Go ◽  
Annie K. van Zanten
Keyword(s):  
Cerebrospinal Fluid ◽  
White Matter ◽  
Brain Edema ◽  
Vasogenic Edema ◽  
Colloid Osmotic Pressure ◽  
Freezing Damage ◽  
Content Type ◽  
Edema Fluid ◽  
The Brain ◽  
Fine Print

✓ Edema fluid isolated from cats with cold-induced brain edema was subjected to analysis of electrolyte content, enzyme activities, colloid osmotic pressure and the radioactivity of intravenously injected 99mTc-labeled albumin. The findings corroborate the essential features of vasogenic edema, such as its origin from the blood plasma, its rapid propagation into the white matter of the brain as contrasted with the delayed spread into gray matter, and its contribution to composition of cerebrospinal fluid. Moreover, the elevated activities of cellular enzymes and K+ content of edema fluid point to the admixture with cellular contents due to the freezing damage.

Primary osteogenic sarcoma of the brain

1976 ◽  
Vol 44 (1) ◽  
pp. 92-95 ◽  
Author(s):  
Skip Jacques ◽  
Donald B. Freshwater ◽  
C. Hunter Shelden
Keyword(s):  
Primary Tumor ◽  
Osteogenic Sarcoma ◽  
Mesenchymal Cell ◽  
Bone Scanning ◽  
Content Type ◽  
Autopsy Findings ◽  
Tumor Focus ◽  
The Right ◽  
The Brain ◽  
Fine Print

✓ The authors report a case of primary osteogenic sarcoma of the brain. Negative autopsy findings, complete bone radiographs, and bone-scanning techniques were consistent with a primary tumor focus in the right temporoparietal region of the brain. The authors suggest an origin from a primitive multipotential mesenchymal cell.

Variables affecting the accuracy of stereotactic localization using computerized tomography

1993 ◽  
Vol 79 (5) ◽  
pp. 667-673 ◽  
Author(s):  
Richard D. Bucholz ◽  
Hector W. Ho ◽  
Jason P. Rubin
Keyword(s):  
Computerized Tomography ◽  
Neurosurgical Procedures ◽  
Slice Thickness ◽  
Laptop Computer ◽  
Content Type ◽  
Mean Error ◽  
Critical Areas ◽  
Stereotactic Localization ◽  
The Brain ◽  
Fine Print

✓ Stereotactic localization using computerized tomography (CT) is increasingly employed to guide neurosurgical procedures in crucial areas of the brain such as the brain stem. This technique allows the surgeon to resect a lesion in its entirety while sparing critical areas of the brain. Thus, the parameters used for scanning should be selected for maximum accuracy. While the small pixel size of CT scanners suggests a high degree of precision in localization, there have been few systematic studies of this accuracy. The authors have studied the amount of error in localization created by variables such as CT scan thickness, interscan spacing, size of lesion, and method of computation when using the Brown-Roberts-Wells (BRW) stereotactic system. Over 1000 CT scans were made of a phantom composed of spheres of differing diameter and location. The CT slice thickness was varied from 1.5 to 5.0 mm, and interscan spacing was varied from 0.5 to 3.0 mm. The coordinates of the center of the spheres were calculated independently using the laptop computer supplied with the unit and also by a stereotactic computer which automatically calculates the center of the fiducials. The actual BRW coordinates of the sphere center were obtained using the phantom base and were then compared to the computer-calculated coordinates to determine error in localization. Variables with a significant effect on error included the scan thickness, interscan spacing, and sphere size. The mean error decreased 23% as the scan thickness decreased from 5.0 to 1.5 mm and 45% as the interscan spacing decreased from 3.0 to 0.5 mm. Mean error was greatest for the smallest sphere sizes. The two computational methods did not differ in error. This study suggests that, for critical areas of the brain or for small lesions, a scan thickness of 1.5 mm and interscan spacing of 0.5 mm should be employed.

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