Effects of steroids and nonsteroid anti-inflammatory agents on vascular permeability in a rat glioma model

1986 ◽  
Vol 65 (2) ◽  
pp. 233-237 ◽  
Author(s):  
Howard R. Reichman ◽  
Catherine L. Farrell ◽  
Rolando F. Del Maestro
Keyword(s):  
Brain Tumors ◽  
Steroid Therapy ◽  
Evans Blue ◽  
Blue Staining ◽  
Blue Dye ◽  
Content Type ◽  
Evans Blue Dye ◽  
Protein Extravasation ◽  
Anti Inflammatory ◽  
Fine Print

✓ Cerebral edema produced by brain tumors is clinically and experimentally reduced by steroid therapy. Nonsteroid anti-inflammatory drugs (NSAID's) which have been used to treat non-neural inflammation and swelling have not been evaluated for their ability to affect edema produced by brain tumors. The authors have used the rat C6 glioma spheroid implantation model to compare the effects of two steroids (dexamethasone and methylprednisolone) and two NSAID's (ibuprofen and indomethacin) on protein extravasation caused by intracranial gliomas. Evans blue dye was used as a marker for serum albumin extravasation. The concentration of Evans blue dye was measured in the tumor and peritumoral and contralateral brain tissue 1 hour after intravenous injection. Extravasation of Evans blue dye within the tumor was decreased in all treatment groups when compared to placebo-injected control animals. The differences between the control specimens and those treated with dexamethasone, methylprednisolone, and indomethacin were highly significant (p < 0.005). The Evans blue staining was also decreased in the peritumoral and contralateral brain. These results indicate that NSAID's compare favorably with steroids in diminishing tumor-induced protein extravasation. It is suggested that NSAID's may prove to be beneficial in clinical instances used either in conjunction with steroid therapy or alone when steroids are contraindicated.

The influence of systemic arterial pressure and intracranial pressure on the development of cerebral vasogenic edema

1983 ◽  
Vol 59 (5) ◽  
pp. 803-809 ◽  
Author(s):  
Quentin J. Durward ◽  
Rolando F. Del Maestro ◽  
A. Loren Amacher ◽  
J. Keith Farrar
Keyword(s):  
Blood Pressure ◽  
Arterial Pressure ◽  
Blood Brain Barrier ◽  
Evans Blue ◽  
Vasogenic Edema ◽  
Brain Barrier ◽  
Blue Dye ◽  
Content Type ◽  
Evans Blue Dye ◽  
Fine Print

✓ The influence of intracranial pressure (ICP), systemic arterial pressure (SAP), and cerebral perfusion pressure (CPP) upon the development of vasogenic cerebral edema is largely unknown. To study their relationship, the authors have produced an osmotic disruption of the blood-brain barrier unilaterally in rabbits by injecting 1 cc/kg of 2M NaCl into the left internal carotid artery. The amount of vasogenic edema produced was assessed by quantitation of the extravasation of Evans blue dye into the area of maximum blood-brain barrier breakdown by means of optical densitometry following formamide extraction. The ICP was measured using a cisterna magna catheter into which mock cerebrospinal fluid could be infused at a predetermined pressure. The SAP was controlled by exsanguination from a femoral artery catheter. In 18 animals in which blood pressure was not controlled, no significant relationship between the ICP and the degree of Evans blue dye extravasation was noted. In these animals, however, a direct relationship between CPP (defined as mean arterial pressure minus mean ICP) and extravasation of Evans blue dye was found (correlation coefficient 0.630; p < 0.001). When ICP was held constant at 0 to 5 mm Hg in another group of 16 animals and different levels of blood pressure were produced by exsanguination, a significant direct relationship between extravasation of Evans blue dye and the SAP was found (correlation coefficient 0.786; p < 0.001). In a third group of 20 animals, the blood pressure was held constant at 90 to 100 mm Hg and the ICP was varied between 0 and 75 mm Hg. There was a highly significant result indicating increasing Evans blue dye extravasation with lower levels of ICP (p < 0.001). Cerebral blood flow determinations by the hydrogen clearance method indicated loss of autoregulation in all animals in the areas of brain injured by intracarotid hypertonic saline. These results indicate that high SAP and low ICP (that is, a large CPP) promote Evans blue dye extravasation in this model of blood-brain barrier disruption. This finding has implications for the management of patients with vasogenic edema.

Focal brain edema associated with acute arterial hypertension

1986 ◽  
Vol 64 (4) ◽  
pp. 643-649 ◽  
Author(s):  
Shizuo Hatashita ◽  
Julian T. Hoff ◽  
Shozo Ishii
Keyword(s):  
Blood Pressure ◽  
Arterial Hypertension ◽  
Water Content ◽  
Brain Edema ◽  
Evans Blue ◽  
Blue Dye ◽  
Boundary Zone ◽  
Tissue Pressure ◽  
Content Type ◽  
Fine Print

✓ Acute arterial hypertension was studied in normal cats to determine its role in the formation of brain edema. Arterial hypertension was induced for 30 minutes by inflation of a balloon catheter situated in the descending aorta. Cerebral edema was evaluated by gross and microscopic observations, tissue water content by wet/dry weights, and blood-brain barrier (BBB) permeability by extravasation of horseradish peroxidase (HRP) and Evans blue dye. For 1 hour after the hypertensive insult, tissue pressure and regional cerebral blood flow (rCBF) were measured from the arterial boundary zone and from a non-boundary region, and intracranial pressure was recorded from the lateral ventricle as ventricular fluid pressure. Focal lesions with increased BBB permeability to Evans blue dye or HRP were usually located symmetrically in the cortex, corresponding to the occipitoparietal parts of the arterial boundary zones. The increase in water content was found only in areas of increased permeability. Tissue pressure increased simultaneously with the abrupt rise in blood pressure, and an increase in rCBF paralleled the elevation of blood pressure. Tissue pressure and rCBF returned to a steady state when blood pressure returned to normal. There were no differences in tissue pressure or rCBF between the arterial boundary zone and the non-boundary zone, even during arterial hypertension. In cerebral hemispheres examined 48 hours after the hypertensive challenge, brain edema had not continued to develop. The data indicate that acute arterial hypertension may produce focal brain edema with increased permeability of the BBB in the cortex of normal brain, particularly in the arterial boundary zones. The authors postulate that increased cerebral blood volume, high intraluminal pressure, and breakthrough of autoregulation play an important role in the formation of hypertensive brain edema.

Pharmacokinetics of controlled-release polymers in the subarachnoid space after subarachnoid hemorrhage in rabbits

2004 ◽  
Vol 101 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Gustavo Pradilla ◽  
Paul P. Wang ◽  
Federico G. Legnani ◽  
James L. Frazier ◽  
Rafael J. Tamargo
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Controlled Release ◽  
Evans Blue ◽  
Subarachnoid Space ◽  
Blue Dye ◽  
Content Type ◽  
Cisterna Magna ◽  
Pharmacokinetic Properties ◽  
Fine Print

Object. Implantation of controlled-release polymers into the subarachnoid space to deliver drugs for treatment of vasospasm after subarachnoid hemorrhage (SAH) is currently of interest. Among the issues regarding local delivery of drugs in the subarachnoid space, however, are the extent of diffusion and the rate of release of the loaded agents. In this study Evans blue dye (EBD) was loaded into controlled-release polymers and its pharmacokinetic properties were determined in vitro and in vivo by using a rabbit model of SAH. Methods. Ethylene—vinyl acetate copolymer (EVAc) was loaded 40% (w:w) with EBD and its pharmacokinetics were spectrophotometrically determined in vitro by examining three EBD—EVAc polymers. Additional polymers were implanted either into the frontal lobe or into the cisterna magna of 16 New Zealand White rabbits. Subarachnoid hemorrhage was induced in eight of the animals by an injection of 1.5 ml of arterial blood into the cisterna magna. The animals were killed 3 or 14 days postoperatively, their brains and spinal cords were harvested, and samples of each were placed in formamide for dye extraction and quantification. Specimens were examined macroscopically and the concentrations of EBD were determined with the aid of a spectrophotometer. The EBD—EVAc polymers continuously released EBD over a 133-day period. The controlled release of the dye into the subarachnoid space in either location resulted in staining of the entire central nervous system (CNS) in rabbits when the polymers were placed either on the frontal lobe or in the cisterna magna. The EBD diffusion covered a distance of at least 40 cm. The presence of blood in the subarachnoid space did not interfere with the diffusion. Conclusions. In this study the authors define the rate and extent of diffusion of EBD from controlled-release polymers placed in the subarachnoid space under conditions of SAH. Evans blue dye diffused through the entire rabbit CNS, covering a distance greater than that of the longest dimension of the hemicircumference of the subarachnoid space around the human brain. The pharmacokinetic properties of EBD—EVAc polymers are comparable to those of antivasospasm agents that are successfully used in animal models of SAH.

Protective effect of the iron chelator deferoxamine on cold-induced brain edema

1989 ◽  
Vol 71 (2) ◽  
pp. 233-238 ◽  
Author(s):  
Yukio Ikeda ◽  
Kiyomi Ikeda ◽  
Donlin M. Long
Keyword(s):  
Specific Gravity ◽  
Brain Edema ◽  
Evans Blue ◽  
Iron Chelator ◽  
Blue Dye ◽  
Content Type ◽  
Group 3 ◽  
Group 2 ◽  
Fine Print ◽  
Group 1

✓ Oxygen free radicals such as superoxide radical and iron-catalyzed hydroxyl radical generated by the superoxide system have been implicated in the genesis of brain edema. Therefore, deferoxamine (DFO), an iron chelator, could potentially be used to treat brain edema. To examine this hypothesis, vasogenic brain edema was produced in 48 cats by a cortical freezing lesion. The animals were separated into three groups: Group 1 comprised 14 cats that received no DFO and were sacrificed at 6 or 24 hours; Group 2 consisted of 12 cats that were treated with DFO (50 mg/kg/ml, intravenously) at 15 minutes before the lesion was made and 60 minutes later and were sacrificed at 6 or 24 hours; and Group 3 included 12 cats that were treated with DFO (50 mg/kg/ml, intravenously) at 15 minutes after the lesion was produced and 60 minutes later and were sacrificed at 6 or 24 hours. The effect of DFO on arterial blood pressure was also studied in the remaining 10 cats. Brain water content in eight sampling areas was measured by the specific gravity method. Blood-brain barrier disruption was assessed by spread of Evans blue dye with planimetry. Specific gravity values at 6 and 24 hours were significantly higher in Group 2 than in Group 1 animals. Areas of Evans blue dye extravasation at 6 and 24 hours were significantly reduced in Group 2 relative to Group 1. Group 3 cats showed improvement in specific gravity values and Evans blue extravasation at 6 hours, but not at 24 hours. The iron chelator DFO prevented early development of brain edema; thus, this oxygen free radical scavenger may provide a foundation for a new therapy for brain edema.

Early alterations in cerebral hemodynamics, brain metabolism, and blood-brain barrier permeability in experimental intracerebral hemorrhage

1999 ◽  
Vol 91 (6) ◽  
pp. 1013-1019 ◽  
Author(s):  
E-Jian Lee ◽  
Yu-Chang Hung ◽  
Ming-Yang Lee
Keyword(s):  
Intracerebral Hemorrhage ◽  
Blood Brain Barrier ◽  
Evans Blue ◽  
Trypan Blue ◽  
Brain Barrier ◽  
Blue Dye ◽  
Content Type ◽  
Group A ◽  
Group B ◽  
Fine Print

Object. The authors sought to ascertain the nature of the hemodynamic and metabolic derangement underlying acute pathophysiological events that occur after intracerebral hemorrhage (ICH).Methods. Cerebral perfusion pressure (CPP), flow velocity (FV) of the middle cerebral artery, and the arteriovenous contents of oxygen and lactate were investigated in 24 dogs subjected to sham operations (Group A, four animals) or intracerebral injections of 3 ml (Group B, 11 animals) or 5 ml (Group C, nine animals) autologous arterial blood. Twelve additional dogs received intravenous injections of 2% Evans blue or trypan blue dye to evaluate blood-brain barrier (BBB) changes. Within 1 hour, animals with ICH exhibited a rise in FV associated with significant reductions (p < 0.05) in CPP and the arteriovenous content difference (AVDO2). In Group C animals significant increases in lactate concentration were found in arterial and superior sagittal sinus (SSS) samples compared with those in the other two groups (p < 0.05). Additionally, perihematomal dye extravasation was observed in animals subjected to ICH and trypan blue dye injections, with profound and mild leakages in Group C and Group B animals, respectively, but not in Group A and Evans blue dye—injected animals. During the subsequent 4 hours, the FV and AVDO2 returned to normal in Group B animals, indicating a balanced cerebral metabolic rate for oxygen (CMRO2) compared with a deranged CMRO2 in Group C animals due to their lowered FV and AVDO2. However, no coupling increase in brain lactate clearance in Group C animals accounted for either the early lactate elevation in SSS or the decrease in CMRO2.Conclusions. Profound reductions in CPP and brain oxygenation after ICH may rapidly exhaust hemodynamic compensation and, thus, impede cerebral homeostasis; however, these reductions only modestly enhance anaerobic glycolysis. Furthermore, the data suggest that a selective increase in permeability, rather than anatomical disruption, of the BBB is involved in the acute pathophysiological events that occur after ICH, which may provide a possible gateway for systemic arterial lactate entering the SSS.

The integration of metabolic imaging in stereotactic procedures including radiosurgery: a review

2002 ◽  
Vol 97 ◽  
pp. 542-550 ◽  
Author(s):  
Marc Levivier ◽  
David Wikler ◽  
Nicolas Massager ◽  
Philippe David ◽  
Daniel Devriendt ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Tumors ◽  
Treatment Planning ◽  
Target Volume ◽  
Emission Tomography ◽  
Low Grade ◽  
Content Type ◽  
Positron Emission ◽  
Pet Scanning ◽  
Fine Print

Object. The authors review their experience with the clinical development and routine use of positron emission tomography (PET) during stereotactic procedures, including the use of PET-guided gamma knife radiosurgery (GKS). Methods. Techniques have been developed for the routine use of stereotactic PET, and accumulated experience using PET-guided stereotactic procedures over the past 10 years includes more than 150 stereotactic biopsies, 43 neuronavigation procedures, and 34 cases treated with GKS. Positron emission tomography—guided GKS was performed in 24 patients with primary brain tumors (four pilocytic astrocytomas, five low-grade astrocytomas or oligodendrogliomas, seven anaplastic astrocytomas or ependymomas, five glioblastomas, and three neurocytomas), five patients with metastases (single or multiple lesions), and five patients with pituitary adenomas. Conclusions. Data obtained with PET scanning can be integrated with GKS treatment planning, enabling access to metabolic information with high spatial accuracy. Positron emission tomography data can be successfully combined with magnetic resonance imaging data to provide specific information for defining the target volume for the radiosurgical treatment in patients with recurrent brain tumors, such as glioma, metastasis, and pituitary adenoma. This approach is particularly useful for optimizing target selection for infiltrating or ill-defined brain lesions. The use of PET scanning contributed data in 31 cases (93%) and information that was specifically utilized to adapt the target volume in 25 cases (74%). It would seem that the integration of PET data into GKS treatment planning may represent an important step toward further developments in radiosurgery: this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors.

Gamma knife radiosurgery for metastatic brain tumors from lung cancer: a comparison between small cell and non—small cell carcinoma

2002 ◽  
Vol 97 ◽  
pp. 484-488 ◽  
Author(s):  
Toru Serizawa ◽  
Junichi Ono ◽  
Toshihiko Iichi ◽  
Shinji Matsuda ◽  
Makoto Sato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Tumors ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
Small Cell ◽  
Metastatic Brain Tumors ◽  
Cell Lung Carcinoma ◽  
Content Type ◽  
Significant Difference ◽  
Fine Print

Object. The purpose of this retrospective study was to evaluate the effectiveness of gamma knife radiosurgery (GKS) for the treatment of metastatic brain tumors from lung cancer, with particular reference to small cell lung carcinoma (SCLC) compared with non-SCLC (NSCLC). Methods. Two hundred forty-five consecutive patients meeting the following five criteria were evaluated in this study: 1) no prior brain tumor treatment; 2) 25 or fewer lesions; 3) a maximum of three tumors with a diameter of 20 mm or larger; 4) no surgically inaccessible tumor 30 mm or greater in diameter; and 5) more than 3 months of life expectancy. According to the same treatment protocol, large tumors (≥ 30 mm) were surgically removed and the other small lesions (< 30 mm) were treated with GKS. New lesions were treated with repeated GKS. Chemotherapy was administered, according to the primary physician's protocol, as aggressively as possible. Progression-free, overall, neurological, qualitative, and new lesion—free survival were calculated with the Kaplan—Meier method and were compared in the SCLC and NSCLC groups by using the log-rank test. The poor prognostic factors for each type of survival were also analyzed with the Cox proportional hazard model. Conclusions. Tumor control rate at 1 year was 94.5% in the SCLC group and 98% in the NSCLC group. The median survival time was 9.1 months in the SCLC group and 8.6 months in the NSCLC group. The 1-year survival rates in the SCLC group were 86.5% for neurological survival and 68.9% for qualitative survival; those in the NSCLC group were 87.9% for neurological and 78.9% for qualitative survival. The estimated median interval to emergence of a new lesion was 6.9 months in the SCLC group and 9.8 months in the NSCLC group. There was no significant difference between the two groups for any type of survival; this finding was verified by multivariate analysis. The results of this study suggest that GKS appears to be as effective in treating brain metastases from SCLC as for those from NSCLC.

Does gamma knife surgery stimulate cellular immune response to metastatic brain tumors? A histopathological and immunohistochemical study

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 180-184 ◽  
Author(s):  
György T. Szeifert ◽  
Isabelle Salmon ◽  
Sandrine Rorive ◽  
Nicolas Massager ◽  
Daniel Devriendt ◽  
...  
Keyword(s):  
Immune Response ◽  
Brain Tumors ◽  
Gamma Knife ◽  
Cellular Immune Response ◽  
Lymphocytic Infiltration ◽  
Gamma Knife Surgery ◽  
Metastatic Brain Tumors ◽  
Content Type ◽  
Cellular Immune ◽  
Fine Print

Object. The aim of this study was to analyze the cellular immune response and histopathological changes in secondary brain tumors after gamma knife surgery (GKS). Methods. Two hundred ten patients with cerebral metastases underwent GKS. Seven patients underwent subsequent craniotomy for tumor removal between 1 and 33 months after GKS. Four of these patients had one tumor, two patients had two tumors, and one patient had three. Histological and immunohistochemical investigations were performed. In addition to routine H & E and Mallory trichrome staining, immunohistochemical reactions were conducted to characterize the phenotypic nature of the cell population contributing to the tissue immune response to neoplastic deposits after radiosurgery. Light microscopy revealed an intensive lymphocytic infiltration in the parenchyma and stroma of tumor samples obtained in patients in whom surgery was performed over 6 months after GKS. Contrary to this, extensive areas of tissue necrosis with either an absent or scanty lymphoid population were observed in the poorly controlled neoplastic specimens obtained in cases in which surgery was undertaken in patients less than 6 months after GKS. Immunohistochemical characterization demonstrated the predominance of CD3-positive T cells in the lymphoid infiltration. Conclusions. Histopathological findings of the present study are consistent with a cellular immune response of natural killer cells against metastatic brain tumors, presumably stimulated by the ionizing energy of focused radiation.

Thymidine kinase-mediated killing of rat brain tumors

1993 ◽  
Vol 79 (5) ◽  
pp. 729-735 ◽  
Author(s):  
David Barba ◽  
Joseph Hardin ◽  
Jasodhara Ray ◽  
Fred H. Gage
Keyword(s):  
Gene Therapy ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Wild Type ◽  
Cns Disorders ◽  
Content Type ◽  
Potential Applications ◽  
Ganciclovir Treatment ◽  
The Brain ◽  
Fine Print

✓ Gene therapy has many potential applications in central nervous system (CNS) disorders, including the selective killing of tumor cells in the brain. A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir. The HSV-TK gene was introduced in vitro into tumor cells (C6-TK and 9L-TK), then these modified tumor cells were evaluated for their sensitivity to cell killing by ganciclovir. In a dose-response assay, both C6-TK and 9L-TK cells were 100 times more sensitive to killing by ganciclovir (median lethal dose: C6-TK, 0.1 µg ganciclovir/ml; C6, 5.0 µg ganciclovir/ml) than unmodified wild-type tumor cells or cultured fibroblasts. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to kill established brain tumors in rats as quantified by both stereological assessment of brain tumor volumes and studies of animal survival over 90 days. Rats with brain tumors established by intracerebral injection of wild-type or HSV-TK modified tumor cells or by a combination of wild-type and HSV-TK-modified cells were studied with and without ganciclovir treatments. Stereological methods determined that ganciclovir treatment eliminated tumors composed of HSV-TK-modified cells while control tumors grew as expected (p < 0.001). In survival studies, all 10 rats with 9L-TK tumors treated with ganciclovir survived 90 days while all untreated rats died within 25 days. Curiously, tumors composed of combinations of 9L and 9L-TK cells could be eliminated by ganciclovir treatments even when only one-half of the tumor cells carried the HSV-TK gene. While not completely understood, this additional tumor cell killing appears to be both tumor selective and local in nature. It is concluded that HSV-TK gene therapy with ganciclovir treatment does selectively kill tumor cells in the brain and has many potential applications in CNS disorders, including the treatment of cancer.

scholarly journals Evans Blue Dye as an in vivo marker of myofibre damage: optimising parameters for detecting initial myofibre membrane permeability

2002 ◽  
Vol 200 (1) ◽  
pp. 69-79 ◽  
Author(s):  
P. W. Hamer ◽  
J. M. McGeachie ◽  
M. J. Davies ◽  
M. D. Grounds
Keyword(s):  
Membrane Permeability ◽  
Evans Blue ◽  
Blue Dye ◽  
Evans Blue Dye
Sign in / Sign up

Export Citation Format

Share Document