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.

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.

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.

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.

Impaired capillary perfusion and brain edema following experimental subarachnoid hemorrhage: a morphometric study

1990 ◽  
Vol 73 (3) ◽  
pp. 410-417 ◽  
Author(s):  
Hiroo Johshita ◽  
Neal F. Kassell ◽  
Tomio Sasaki ◽  
Hisayuki Ogawa
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Stem ◽  
Brain Edema ◽  
Blood Volume ◽  
Evans Blue ◽  
Piriform Cortex ◽  
Capillary Perfusion ◽  
Content Type ◽  
Intercapillary Distance ◽  
Fine Print

✓ To evaluate microcirculatory disturbance and cerebral edema associated with subarachnoid hemorrhage (SAH), both stereological morphometry on the intraparenchymal capillary network and microgravimetry were performed on a rabbit SAH model. Autologous arterial blood (5 ml) was injected into the cisterna magna, and the animals were sacrificed at intervals of 6 hours, 1 day, 2 days, or 6 days after SAH. Capillaries in the piriform cortex, parasagittal cortex, and ventral brain stem of the midline-hemisectioned brain were injected with Evans blue dye 1 minute before sacrifice, and were planimetrically evaluated under a fluorescence microscope connected to an image analysis system. Stereological and morphological parameters including the volume density, surface density, numerical density, minimum intercapillary distance, and the diameter of Evans blue-perfused capillaries were also computed. In the piriform cortex and ventral brain stem, the volume and surface densities were significantly reduced and the minimum intercapillary distance was significantly increased 1 to 2 days after SAH. In the parasagittal cortex far from the cisternal clot, changes in the parameters were minimal. Cerebral blood volume (CBV) in the normal condition and edema formation associated with SAH were studied by the microgravimetric technique. The mean CBV in the parasagittal cortex, piriform cortex, and brain stem was 6.9%, 6.8%, and 5.6%, respectively. Following SAH, specific gravity in the piriform cortex and the ventral brain stem of the other side of the hemisectioned brain was significantly decreased at 1 to 2 days, showing a change parallel to that of the stereological parameters. The results obtained from the morphometric technique indicated the occurrence of impaired capillary perfusion and reduced capillary blood volume following SAH, while microgravimetry suggested the formation of brain edema during this period. These changes in the intraparenchymal vessels may play an important role in the pathophysiology of SAH.

Correlations between the apparent diffusion coefficient, water content, and ultrastructure after induction of vasogenic brain edema in cats

1999 ◽  
Vol 90 (3) ◽  
pp. 499-503 ◽  
Author(s):  
Toshihiko Kuroiwa ◽  
Tsukasa Nagaoka ◽  
Masato Ueki ◽  
Ichiro Yamada ◽  
Naoyuki Miyasaka ◽  
...  
Keyword(s):  
White Matter ◽  
Water Content ◽  
Brain Edema ◽  
Nerve Fibers ◽  
Tissue Water ◽  
Content Type ◽  
Deep White Matter ◽  
Vasogenic Brain Edema ◽  
Apparent Diffusion ◽  
Fine Print

Object. The authors examined the correlation between changes in the apparent diffusion coefficient, regional water content, and tissue ultrastructure after vasogenic brain edema.Methods. Vasogenic edema was induced in the white matter of six cats by cortical cold lesioning. The trace of diffusion tensor (Trace[D]) obtained from magnetic resonance imaging to measure the orientationally averaged water diffusibility was compared with the corresponding tissue water content determined by gravimetric studies and with ultrastructural water localization. Edema fluid had spread to the subcortical and deep white matter by 4.5 hours postlesioning. The increase in Trace(D) showed a significant linear correlation with the increase in tissue water content, both in the subcortical and deep white matter as follows: y = 45.5x − 2367 (r = 0.94) and y = 37.0x − 1769 (r = 0.93), respectively, where x is the water content (gram water/gram tissue) and y the Trace(D) (× 10−6 mm2/second). On histological examination, nerve fibers were found to be dissociated in the white matter and the extracellular space was markedly enlarged with protein-rich fluid. No noticeable hydropic swelling of the cellular components was observed.Conclusions. A linear correlation was observed between increases in Trace(D) and increases in extracellular water volume in in vivo vasogenic brain edema. A similar correlation between the subcortical and deep white matter showing different arrangements of nerve fibers (parallel compared with intermingled, respectively) indicated that measurement of Trace(D) is a suitable parameter for the evaluation of vasogenic brain edema.

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 kallikrein-kinin system as mediator in vasogenic brain edema

1984 ◽  
Vol 61 (1) ◽  
pp. 87-96 ◽  
Author(s):  
Andreas Unterberg ◽  
Alexander J. Baethmann
Keyword(s):  
White Matter ◽  
Water Content ◽  
Brain Edema ◽  
Cerebral Edema ◽  
Vasogenic Edema ◽  
Ventricular System ◽  
Periventricular White Matter ◽  
Content Type ◽  
Vasogenic Brain Edema ◽  
Fine Print

✓ Plasma and bradykinin were perfused into the ventricular system of mongrel dogs to investigate whether either or both induce brain edema. Formation of cerebral edema was determined by measurement of cerebral water and electrolytes in periventricular white matter, cerebral cortex, and caudate nucleus. The response of cerebral tissue to exposure to bradykinin or to plasma, as a carrier of kininogens, was analyzed by assessment of the perfusate composition after ventricle passage. The authors report that cerebral administration of bradykinin induces cerebral edema. Ventricular perfusion with plasma also led to an increase of cerebral water content which was restricted to the white matter, but involved all brain tissue areas, if bradykinin was used. Ventricular perfusion with plasma was associated with consumption of the kinin precursor (kininogens) indicative of formation of kinins. Significant consumption of the precursor was found in five out of nine animals subjected to plasma perfusion of the ventricular system. In these animals a close correlation between the increase of white matter water content and kininogen-consumption as a measure of kinin-formation was obtained. Marked kinin-degrading activity was observed during ventricular perfusion with bradykinin as concluded from a considerable decrease of bradykinin concentration in the cisternal effluent compared to the inflowing perfusate concentration. Ventricular perfusion with plasma was associated with a decrease of K+ clearance capacity with continued duration, and in two animals with a release of glutamate into the plasma perfusate, suggesting an involvement of cytotoxic mechanisms. These findings provide support for the hypothesis of a mediator function of the kallikrein-kinin (KK) system in vasogenic brain edema. The next question that needs to be answered to complete the picture — does spontaneous activation of the KK system occur in conditions leading to vasogenic edema? — is studied in a subsequent report.

Neuroprotective effects of citicoline on brain edema and blood—brain barrier breakdown after traumatic brain injury

2000 ◽  
Vol 92 (3) ◽  
pp. 448-452 ◽  
Author(s):  
Mustafa K. Başkaya ◽  
Aclan Doğan ◽  
A. Muralikrishna Rao ◽  
Robert J. Dempsey
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blue Dye ◽  
Neuroprotective Effects ◽  
Content Type ◽  
Blood Brain ◽  
Fine Print

Object. Cytidine 5′-diphosphocholine (CDPC), or citicoline, is a naturally occurring endogenous compound that has been reported to provide neuroprotective effects after experimental cerebral ischemia. However, in no study has such protection been shown after traumatic brain injury (TBI). In this study the authors examined the effect of CDPC on secondary injury factors, brain edema and blood-brain barrier (BBB) breakdown, after TBI.Methods. After anesthesia had been induced in Sprague—Dawley rats by using 1.5% halothane, an experimental TBI was created using a controlled cortical impact (CCI) device with a velocity of 3 m/second, resulting in a 2-mm deformation. Four sham-operated control animals used for brain edema and BBB breakdown studies underwent the same surgical procedure, but received no injury. Brain edema was evaluated using the wet—dry method 24 hours postinjury, and BBB breakdown was evaluated by measuring Evans blue dye (EBD) extravasation with fluorescein 6 hours after TBI. The animals received intraperitoneal injections of CDPC (50, 100, or 400 mg/kg two times after TBI [eight–10 animals in each group]) or saline (eight animals) after TBI. Traumatic brain injury induced an increase in the percentage of water content and in EBD extravasation in the injured cortex and the ipsilateral hippocampus. No significant benefit from CDPC treatment was observed at a dose of 50 mg/kg. Cytidine 5′-diphosphocholine at a dose of 100 mg/kg attenuated EBD extravasation in both regions, although it reduced brain edema only in the injured cortex. In both regions, 400 mg/kg of CDPC significantly decreased brain edema and BBB breakdown.Conclusions. This is the first report in which dose-dependent neuroprotective effects of CDPC have been demonstrated in the injured cortex as well as in the hippocampus, a brain region known to be vulnerable to injury, after experimental TBI. The results of this study suggest that CDPC is an effective neuroprotective agent on secondary injuries that appear following TBI.

Effects of tromethamine and hyperventilation on brain injury in the cat

1991 ◽  
Vol 74 (1) ◽  
pp. 87-96 ◽  
Author(s):  
Kazuo Yoshida ◽  
Anthony Marmarou
Keyword(s):  
Water Content ◽  
Brain Edema ◽  
Brain Tissue ◽  
Mr Spectroscopy ◽  
Content Type ◽  
Fluid Percussion Injury ◽  
Brain Ph ◽  
The Brain ◽  
Brain Lactate ◽  
Fine Print

✓ The metabolic brain acidosis after trauma has been thought to be harmful and to contribute to neurological deterioration. Amelioration of the brain acidosis either by systemic buffering agents or by hyperventilation has been proposed as a method of treatment. The objective of this study was to explore with magnetic resonance (MR) spectroscopy the metabolic changes in brain that occur with the use of hyperventilation, THAM (tromethamine; tris[hydroxymethyl]aminomethane), and a combination (THAM and hyperventilation) therapy in experimental fluid-percussion injury. Brain lactate, brain pH, inorganic phosphate (Pi), and adenosine triphosphate levels were measured by 1H and 31P MR spectroscopy. Arterial and cerebrovenous lactate and water content in brain tissue was determined in 29 cats using the specific gravimetric technique. Following injury, the phosphocreatine (PCr)/Pi ratio, which is an index of cerebral energy depletion, decreased to 76% in four untreated animals, to 79% in 11 THAM-treated animals, to 68% in seven animals receiving hyperventilation, and to 66% in seven animals with combination THAM and hyperventilation therapy. The PCr/Pi ratio returned to a normal level in 8 hours in animals treated with THAM and THAM in combination with hyperventilation. The brain lactate index increased to 157% in the hyperventilation group after trauma. In cats receiving THAM plus hyperventilation, the brain lactate index was reduced to 142%, while the minimum rise of 126% was associated with treatment of THAM alone. In the THAM-treatment and combination-treatment groups, the water content of the white and gray matter was significantly decreased compared with that in untreated cat brains. Prolonged hyperventilation provided relative ischemia in brain tissue and promoted more production of brain lactate, no recovery of the PCr/Pi ratio, and no decrease in brain edema. On the other hand, administration of THAM decreased production of brain lactate and brain edema and promoted the recovery of cerebral energy dysfunction. It was found that THAM ameliorates the deleterious effects of hyperventilation by minimizing energy disturbance and that it also decreases brain edema. The authors conclude that THAM may be effective in reducing brain tissue acidosis and helpful as a metabolic stabilizing agent following severe head injury.

The effect of furosemide on intracranial pressure and hemorrhage in preterm rabbits

1989 ◽  
Vol 70 (5) ◽  
pp. 785-792 ◽  
Author(s):  
Antonio V. Lorenzo ◽  
Clarence S. Greene ◽  
Gregory W. Hornig ◽  
L. Manuel Zavala ◽  
Keasley Welch
Keyword(s):  
Blood Pressure ◽  
Intracranial Hypotension ◽  
Intraventricular Hemorrhage ◽  
Fluid Loss ◽  
Tissue Pressure ◽  
Germinal Matrix ◽  
Content Type ◽  
Muscle Water ◽  
The Brain ◽  
Fine Print

✓ The hypothesis that intracranial hypotension due to excessive postnatal fluid loss places the premature infant at risk for germinal matrix and intraventricular hemorrhage (GM-IVH) was tested in preterm rabbits delivered at 28 and 29 days of gestation (term 32 days). Furosemide administered to newborn pups induced a diuresis that resulted in a 11% to 22% loss in body weight and a concomitant decline in muscle water (13% to 16%) and sodium (18% to 21%). Paradoxically, no change occurred in the water or electrolyte content of the brain even though cerebrospinal fluid and brain tissue pressure, but not blood pressure, declined. These changes were absent in littermates treated with saline. Microscopic examination of brain sections revealed a greater incidence of intracranial hemorrhage, particularly in the germinal matrix and choroid plexus, in furosemide-treated than in saline-treated preterm rabbit pups. These results are consistent with the hypothesis that intracranial hypotension promotes the incidence of GH-IVH in preterm animals.

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