Contribution of vasogenic and cellular edema to traumatic brain swelling measured by diffusion-weighted imaging

1997 ◽  
Vol 87 (6) ◽  
pp. 900-907 ◽  
Author(s):  
Pál Barzó ◽  
Anthony Marmarou ◽  
Panos Fatouros ◽  
Koji Hayasaki ◽  
Frank Corwin
Keyword(s):  
Water Content ◽  
Diffusion Weighted Imaging ◽  
Vasogenic Edema ◽  
Brain Water Content ◽  
Brain Swelling ◽  
Edema Formation ◽  
Content Type ◽  
Diffusion Weighted ◽  
Brain Water ◽  
Fine Print

✓ The contribution of brain edema to brain swelling in cases of traumatic brain injury remains a critical problem. The authors believe that cellular edema, the result of complex neurotoxic events, is the major contributor to brain swelling and that vasogenic edema, secondary to blood-brain barrier compromise, may be overemphasized. The objective of this study, therefore, was to quantify temporal water content changes and document the type of edema that forms during the acute and late stages of edema development following closed head injury (CHI). The measurement of brain water content was based on magnetic resonance imaging—determined values of tissue longitudinal relaxation time (T1-weighted imaging) and their subsequent conversion to percentage of water, whereas the differentiation of edema formation (cellular vs. vasogenic) was based on the measurement of the apparent diffusion coefficient (ADC) by diffusion-weighted imaging. A new impact-acceleration model was used to induce CHI. Thirty-six adult Sprague—Dawley rats were separated into two groups: Group I, control (six animals); and Group II, trauma (30 animals). Fast ADC measurements (localized, single-voxel) were obtained sequentially (every minute) up to 1 hour postinjury. The T1-weighted images, used for water content determination, and the diffusion-weighted images (ADC measurement with conventional diffusion-weighted imaging) were obtained at the end of the 1st hour postinjury and on Days 1, 3, 7, 14, 28, and 42 in animals from the trauma and control groups. In the animals subjected to trauma, the authors found a significant increase in ADC (10 ± 5%) and brain water content (1.3 ± 0.9%) during the first 60 minutes postinjury. This is consistent with an increase in the volume of extracellular fluid and vasogenic edema formation as a result of blood-brain barrier compromise. This transient increase, however, was followed by a continuing decrease in ADC that began 40 to 60 minutes postinjury and reached a minimum value on Days 7 to 14 (10 ± 3% reduction). Because the water content of the brain continued to increase during the first 24 hours postinjury (1.9 ± 0.9%), it is suggested that the decreased ADC indicated cellular edema formation, which started to develop soon after injury and became dominant between 1 and 2 weeks postinjury. The study provides supportive evidence that cellular edema is the major contributor to posttraumatic swelling in diffuse CHI and defines the onset and duration of the increase in cellular volume.

Effect of vasopressin on cold-induced brain edema in cats

1986 ◽  
Vol 64 (6) ◽  
pp. 941-950 ◽  
Author(s):  
Ralph F. Reeder ◽  
Eugene E. Nattie ◽  
William G. North
Keyword(s):  
White Matter ◽  
Water Content ◽  
Vasogenic Edema ◽  
High Dose ◽  
Brain Water Content ◽  
Carrier Solution ◽  
Content Type ◽  
Cold Lesion ◽  
Brain Water ◽  
Fine Print

✓ Centrally released arginine vasopressin (AVP) has been implicated in the regulation of intracranial pressure (ICP) and brain water, and is elevated in the cerebrospinal fluid (CSF) of some patients with pseudotumor cerebri or subarachnoid hemorrhage. The authors have examined the relationship of AVP levels in CSF to ICP and brain water content in three experimental groups of cats with and without cold-induced vasogenic edema. With the cats under general anesthesia, a cold lesion was made and cannulas were placed in the cisterna magna, lateral ventricle, and aorta. Subsequent central and systemic measurements were made while the animals were awake and free-roaming. In Experiment 1, endogenous AVP levels in CSF were measured every 12 hours over a 48-hour period by radioimmunoassay in cats with sham craniotomy, mild edema, or moderate edema; no significant difference was found between groups although a diurnal variation was seen (range 2 to 18 pg/ml). In Experiment 2, either carrier solution or AVP, in doses of 1.5 or 30 ng, was administered via a lateral ventricle every 2 hours over 24 hours in unlesioned cats. In Experiment 3, cats received 2 or 35 ng of carrier solution or AVP in a similar manner, but coupled with a cold lesion. The CSF AVP levels ranged from an average of 100 to 681 pg/ml and 1.4 to 11.9 ng/ml in the two dose groups in both experiments. Neither the low nor the high dose had an effect on brain water content in normal white matter (Experiment 2), but both doses increased brain water content in edematous white matter (p < 0.05 in Experiment 3), as determined by wet and dry weight measurements of standardized pieces of white matter. The ICP was decreased by high-dose AVP in normal cats (p < 0.01 at 24 hours), but in lesioned cats was unchanged by low-dose and increased by high-dose AVP (p < 0.05 at 18 hours). The authors conclude that pharmacological doses of central AVP facilitate the production of vasogenic edema.

Significant reduction in brain swelling by administration of nonpeptide kinin B2 receptor antagonist LF 16—0687Ms after controlled cortical impact injury in rats

2000 ◽  
Vol 92 (5) ◽  
pp. 853-859 ◽  
Author(s):  
John F. Stover ◽  
Nils-Kristian Dohse ◽  
Andreas W. Unterberg
Keyword(s):  
Receptor Antagonist ◽  
Water Content ◽  
Brain Edema ◽  
Single Administration ◽  
Brain Swelling ◽  
Edema Formation ◽  
Content Type ◽  
Controlled Cortical Impact Injury ◽  
Impact Injury ◽  
Fine Print

Object. Identification of new therapeutic agents aimed at attenuating posttraumatic brain edema formation remains an unresolved challenge. Among others, activation of bradykinin B2 receptors is known to mediate the formation of brain edema. The purpose of this study was to investigate the protective effect of the novel nonpeptide B2 receptor antagonist, LF 16-0687Ms, in brain-injured rats.Methods. Focal contusion was produced by controlled cortical impact injury. Five minutes after trauma, the rats received a single dose of no, low- (3 mg/kg body weight), or high- (30 mg/kg) dose LF 16-0687Ms. After 24 hours, the amount of brain swelling and hemispheric water content were determined. Low and high doses of LF 16-0687Ms significantly reduced brain swelling by 25% and 27%, respectively (p < 0.03). Hemispheric water content tended to be increased in the nontraumatized hemisphere.In a subsequent series of 10 rats, cisternal cerebrospinal fluid (CSF) samples were collected to determine whether changes in substances associated with edema formation could clarify why LF 16-0687Ms increases water content. For this, the volume regulator amino acid taurine, the excitatory transmitter glutamate, and the adenosine triphosphate degradation products hypoxanthine and xanthine were measured. In CSF, the levels of taurine, hypoxanthine, and xanthine were significantly decreased following a single administration of LF 16-0687Ms (p < 0.005); the level of glutamate, however, was double that found in control animals (p < 0.05).Conclusions. Using the present study design, a single administration of LF 16-0687Ms successfully reduced posttraumatic brain swelling. The decreased levels of taurine, hypoxanthine, and xanthine may reflect reduced posttraumatic brain edema, whereas the increased level of glutamate could account for the elevated water content observed in the nontraumatized hemisphere.

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.

Inhibition of brain glutamine accumulation prevents cerebral edema in hyperammonemic rats

1991 ◽  
Vol 261 (3) ◽  
pp. H825-H829 ◽  
Author(s):  
H. Takahashi ◽  
R. C. Koehler ◽  
S. W. Brusilow ◽  
R. J. Traystman
Keyword(s):  
Water Content ◽  
Cerebral Edema ◽  
Methionine Sulfoximine ◽  
Synthetase Activity ◽  
Glutamine Synthetase Activity ◽  
Brain Water Content ◽  
Brain Swelling ◽  
Reye's Syndrome ◽  
Inborn Errors ◽  
Brain Water

The mechanism of brain swelling during hyperammonemia is not understood, but glutamine accumulation is consistently observed. We tested the hypothesis that brain swelling associated with hyperammonemia is a consequence of the osmotic effect of intracellular glutamine accumulation in brain. Increases in plasma ammonium levels from 31 +/- 3 to 601 +/- 38 mumol/l (+/- SE) were produced by 6 h of infusion of ammonium acetate in anesthetized rats. Hyperammonemia resulted in increased brain water content accompanied by more than a tripling of brain glutamine concentration compared with control rats receiving sodium acetate (5.6 +/- 0.4 vs. 18.8 +/- 0.4 mmol/kg). Inhibition of glutamine synthetase activity by pretreatment with L-methionine sulfoximine prevented both the increase in brain glutamine levels and the increase in brain water content despite elevated plasma ammonium levels (908 +/- 196 mumol/l). Thus cerebral edema during hyperammonemia is associated with glutamine accumulation. We suggest that accumulated glutamine may serve as an idiogenic osmole causing swelling. Because brain swelling eventually leads to increased intracranial pressure and tissue hypoxia, these data suggest a unifying mechanism to account for the many pathophysiological abnormalities found during coma associated with various forms of liver disease, inborn errors of metabolism, and Reye's syndrome.

scholarly journals Microvascular Changes during the Early Phase of Experimental Bacterial Meningitis

1990 ◽  
Vol 10 (6) ◽  
pp. 914-922 ◽  
Author(s):  
H.-W. Pfister ◽  
U. Koedel ◽  
R. L. Haberl ◽  
U. Dirnagl ◽  
W. Feiden ◽  
...  
Keyword(s):  
Free Radicals ◽  
Bacterial Meningitis ◽  
Water Content ◽  
Brain Edema ◽  
Early Phase ◽  
Brain Water Content ◽  
Edema Formation ◽  
Oxygen Derived Free Radicals ◽  
Brain Water ◽  
Brain Edema Formation

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

Brain edema formation and neurological impairment after subarachnoid hemorrhage in rats

2009 ◽  
Vol 111 (5) ◽  
pp. 988-994 ◽  
Author(s):  
Serge C. Thal ◽  
Sonja Sporer ◽  
Mariusz Klopotowski ◽  
Simone E. Thal ◽  
Johannes Woitzik ◽  
...  
Keyword(s):  
Water Content ◽  
Brain Edema ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Neurological Deficits ◽  
Brain Water Content ◽  
Edema Formation ◽  
Neuronal Cell Loss ◽  
Brain Water ◽  
Brain Edema Formation

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

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.

The effect of mannitol on cerebral white matter water content

1986 ◽  
Vol 65 (1) ◽  
pp. 41-43 ◽  
Author(s):  
Fred Nath ◽  
Sam Galbraith
Keyword(s):  
White Matter ◽  
Head Injury ◽  
Specific Gravity ◽  
Water Content ◽  
Subcortical White Matter ◽  
Cerebral White Matter ◽  
Brain Water Content ◽  
Content Type ◽  
The Brain ◽  
Brain Water

✓ The authors have studied the effect of a low-dose (0.28 gm/kg) bolus infusion of mannitol on brain water in man. In eight patients with severe head injury, small pieces of subcortical white matter were taken at craniotomy both before and after infusion of mannitol. The tissue specific gravity was measured using a graduated specific-gravity column, and from it the brain water content was calculated. White matter specific gravity rose from a mean (± standard error of the mean) of 1.0325 ± 0.0012 before mannitol infusion to 1.0352 ± 0.0011 after mannitol administration, and the brain water content fell from a mean of 80.94% ± 2.5% to 75.28% ± 2.3%. The differences were significant (p < 0.01). This study shows that, after head injury in man, mannitol increases the white matter specific gravity and probably does so by reducing brain water.

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.

scholarly journals Glibenclamide does not improve outcome following severe collagenase-induced intracerebral hemorrhage in rats

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252584
Author(s):  
Tiffany F. C. Kung ◽  
Cassandra M. Wilkinson ◽  
Christine A. Dirks ◽  
Glen C. Jickling ◽  
Frederick Colbourne
Keyword(s):  
Intracerebral Hemorrhage ◽  
Water Content ◽  
Transient Receptor Potential ◽  
Neurological Deficits ◽  
Brain Water Content ◽  
Adult Rats ◽  
Edema Formation ◽  
Improve Outcome ◽  
Transient Receptor Potential Melastatin ◽  
Brain Water

Intracerebral hemorrhage (ICH) is a devastating insult with few effective treatments. Edema and raised intracranial pressure contribute to poor outcome after ICH. Glibenclamide blocks the sulfonylurea 1 transient receptor potential melastatin 4 (Sur1-Trpm4) channel implicated in edema formation. While glibenclamide has been found to improve outcome and reduce mortality in animal models of severe ischemic stroke, in ICH the effects are less clear. In our previous study, we found no benefit after a moderate-sized bleed, while others have reported benefit. Here we tested the hypothesis that glibenclamide may only be effective in severe ICH, where edema is an important contributor to outcome. Glibenclamide (10 μg/kg loading dose, 200 ng/h continuous infusion) was administered 2 hours post-ICH induced by collagenase injection into the striatum of adult rats. A survival period of 24 hours was maintained for experiments 1–3, and 72 hours for experiment 4. Glibenclamide did not affect hematoma volume (~81 μL) or other safety endpoints (e.g., glucose levels), suggesting the drug is safe. However, glibenclamide did not lessen striatal edema (~83% brain water content), ionic dyshomeostasis (Na+, K+), or functional impairment (e.g., neurological deficits (median = 10 out of 14), etc.) at 24 hours. It also did not affect edema at 72 h (~86% brain water content), or overall mortality rates (25% and 29.4% overall in vehicle vs. glibenclamide-treated severe strokes). Furthermore, glibenclamide appears to worsen cytotoxic edema in the peri-hematoma region (cell bodies were 46% larger at 24 h, p = 0.0017), but no effect on cell volume or density was noted elsewhere. Overall, these findings refute our hypothesis, as glibenclamide produced no favorable effects following severe ICH.

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