Resolution of brain edema in severe brain injury at controlled high and low intracranial pressures

✓ A series of 87 patients with severe brain injury were studied. Intracranial pressure (ICP) monitoring and external ventricular drainage were used to control ICP at high and low levels. Clearance of ytterbium-169-labeled diethylenetriaminepentaacetic acid (169Yb-DTPA), Evans blue dye, and ventricular cerebrospinal fluid protein was measured at the two ICP levels over consecutive periods of 4 hours to confirm clearance of brain edema. The results support the hypothesis that brain edema is in part absorbed in the cerebrospinal fluid via transventricular flow.

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

Journal of Neurosurgery ◽

10.3171/jns.2000.92.3.0448 ◽

2000 ◽

Vol 92 (3) ◽

pp. 448-452 ◽

Cited By ~ 52

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.

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High-Dosage Cefazolin Achieves Sufficient Cerebrospinal Diffusion To Treat an External Ventricular Drainage-Related Staphylococcus aureus Ventriculitis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01844-18 ◽

2018 ◽

Vol 63 (2) ◽

pp. e01844-18 ◽

Cited By ~ 1

Author(s):

Matthieu Grégoire ◽

Benjamin Gaborit ◽

Colin Deschanvres ◽

Raphaël Lecomte ◽

Guillaume Deslandes ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Cerebrospinal Fluid ◽

Continuous Infusion ◽

External Ventricular Drainage ◽

High Dose ◽

Ventricular Drainage ◽

Content Type

ABSTRACT A patient received continuous infusion of cefazolin 10 g then 8 g daily for an external ventricular drainage-related methicillin-susceptible Staphylococcus aureus (MSSA) ventriculitis. Median free concentrations in the cerebrospinal fluid were 11.9 and 6.1 mg/liter after 10- and 8-g doses, respectively. Free concentrations in the cerebrospinal fluid were always above the MIC usually displayed by methicillin-susceptible Staphylococcus aureus (MSSA) isolates. These results support the use of high-dose cefazolin to achieve sufficient meningeal concentrations.

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Composition of isolated edema fluid in cold-induced brain edema

Journal of Neurosurgery ◽

10.3171/jns.1979.51.1.0070 ◽

1979 ◽

Vol 51 (1) ◽

pp. 70-77 ◽

Cited By ~ 62

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.

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Cerebrospinal fluid antibiotic levels during treatment of shunt infections

Journal of Neurosurgery ◽

10.3171/jns.1980.52.1.0041 ◽

1980 ◽

Vol 52 (1) ◽

pp. 41-46 ◽

Cited By ~ 62

Author(s):

Steven L. Wald ◽

Robert L. McLaurin

Keyword(s):

Cerebrospinal Fluid ◽

Inhibitory Concentration ◽

External Ventricular Drainage ◽

Cerebrospinal Fluid Shunt ◽

Ventricular Drainage ◽

Antibiotic Concentration ◽

Content Type ◽

Intraventricular Injections ◽

Shunt Infections ◽

Fine Print

✓ Twenty patients with documented cerebrospinal fluid shunt infections were treated with daily intraventricular injections of methicillin, cephalothin, or gentamicin without removal of the shunt or external ventricular drainage. Periodic determinations of intraventricular antibiotic concentration revealed significant levels in relation to the established minimum inhibitory concentration in all cases.

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Focal brain edema associated with acute arterial hypertension

Journal of Neurosurgery ◽

10.3171/jns.1986.64.4.0643 ◽

1986 ◽

Vol 64 (4) ◽

pp. 643-649 ◽

Cited By ~ 39

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.

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Intercenter variance in clinical trials of head trauma—experience of the National Acute Brain Injury Study: Hypothermia

Journal of Neurosurgery ◽

10.3171/jns.2001.95.5.0751 ◽

2001 ◽

Vol 95 (5) ◽

pp. 751-755 ◽

Cited By ~ 142

Author(s):

Guy L. Clifton ◽

Sung C. Choi ◽

Emmy R. Miller ◽

Harvey S. Levin ◽

Kenneth R. Smith ◽

...

Keyword(s):

Clinical Trials ◽

Brain Injury ◽

Phase Iii ◽

Severe Brain Injury ◽

Quality Of Data ◽

Content Type ◽

Physiological Variables ◽

Arterial Blood ◽

Present On Admission ◽

Fine Print

Object. In a recently conducted trial of hypothermia in patients with severe brain injury, differences were found in the effects of hypothermia treatment among various centers. This analysis explores the reasons for such differences. Methods. The authors reviewed data obtained in 392 patients treated for severe brain injury. Prerandomization variables, critical physiological variables, treatment variables, and accrual methodologies were investigated among various centers. Hypothermia was found to be detrimental in patients older than the age of 45 years, beneficial in patients younger than 45 years of age in whom hypothermia was present on admission, and without effect in those in whom normothermia was documented on admission. Marginally significant differences (p < 0.054) in the intercenter outcomes of hypothermia-treated patients were likely the result of wide differences in the percentage of patients older than 45 years of age and in the percentage of patients in whom hypothermia was present on admission among centers. The trial sensitivity was likely diminished by significant differences in the incidence of mean arterial blood pressure (MABP) less than 70 mm Hg (p < 0.001) and cerebral perfusion pressure (CPP) less than 50 mm Hg (p < 0.05) but not intracranial pressure (ICP) greater than 25 mm Hg (not significant) among patients in the various centers. Hours of vasopressor usage (p < 0.03) and morphine dose (p < 0.001) and the percentage of dehydrated patients varied significantly among centers (p < 0.001). The participation of small centers increased intercenter variance and diminished the quality of data. Conclusions. For Phase III clinical trials we recommend: 1) a detailed protocol specifying fluid and MABP, ICP, and CPP management; 2) continuous monitoring of protocol compliance; 3) a run-in period for new centers to test accrual and protocol adherence; and 4) inclusion of only centers in which patients are regularly randomized.

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Attenuation of intracerebral hemorrhage and thrombin-induced brain edema by overexpression of interleukin-1 receptor antagonist

Journal of Neurosurgery ◽

10.3171/jns.2001.95.4.0680 ◽

2001 ◽

Vol 95 (4) ◽

pp. 680-686 ◽

Cited By ~ 74

Author(s):

Tetsuya Masada ◽

Ya Hua ◽

Guohua Xi ◽

Guo-Yuan Yang ◽

Julian T. Hoff ◽

...

Keyword(s):

Brain Injury ◽

Basal Ganglia ◽

Intracerebral Hemorrhage ◽

Receptor Antagonist ◽

Brain Edema ◽

Inflammatory Reaction ◽

Interleukin 1 ◽

Edema Formation ◽

Content Type ◽

Fine Print

Object. Adenovirus-mediated overexpression of interleukin-1 receptor antagonist (IL-1ra) attenuates the inflammatory reaction and brain injury that follows focal cerebral ischemia. Recently, an inflammatory reaction after intracerebral hemorrhage (ICH) was identified. In this study the authors examine the hypothesis that overexpression of IL-1ra reduces brain injury (specifically edema formation) after ICH. Methods. Adenoviruses expressing IL-1ra (Ad.RSVIL-1ra) or LacZ, a control protein (Ad.RSVlacZ), or saline were injected into the left lateral cerebral ventricle in rats. On the 5th day after virus injection, 100 µl of autologous blood or 5 U thrombin was infused into the right basal ganglia. Rats with ICH were killed 24 or 72 hours later for measurement of brain water and ion content. Thrombin-treated rats were killed 24 hours later for edema measurements and an assessment of polymorphonuclear leukocyte (PMNL) infiltration by myeloperoxidase (MPO) assay, as well as histological evaluation. Compared with saline-treated and Ad.RSVlacZ—transduced controls, Ad.RSVIL-1ra-transduced rats had significantly attenuated edema in the ipsilateral basal ganglia 3 days after ICH (81.5 ± 0.3% compared with 83.4 ± 0.4% and 83.3 ± 0.5% in control animals). Thrombin-induced brain edema was also reduced in Ad.RSVIL-1ra—treated rats (81.3 ± 0.4% compared with 83.2 ± 0.4% and 82.5 ± 0.4% in control rats). The reduction in thrombin-induced edema was associated with a reduction in PMNL infiltration into the basal ganglia, as assessed by MPO assay (49% reduction) and histological examination. Conclusions. Overexpression of IL-1ra by using an adenovirus vector attenuated brain edema formation and thrombin-induced intracerebral inflammation following ICH. The reduction in ICH-induced edema with IL-1ra may result from reduction of thrombin-induced brain inflammation.

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Eicosanoids in human ventricular cerebrospinal fluid following severe brain injury

Prostaglandins ◽

10.1016/0090-6980(87)90068-2 ◽

1987 ◽

Vol 34 (6) ◽

pp. 877-887 ◽

Cited By ~ 34

Author(s):

J.Y. Westcott ◽

R.C. Murphy ◽

K. Stenmark

Keyword(s):

Cerebrospinal Fluid ◽

Brain Injury ◽

Severe Brain Injury

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Acetylcholine and experimental brain injury

Journal of Neurosurgery ◽

10.3171/jns.1971.35.5.0523 ◽

1971 ◽

Vol 35 (5) ◽

pp. 523-528 ◽

Cited By ~ 23

Author(s):

Bernard Metz

Keyword(s):

Cerebrospinal Fluid ◽

Brain Injury ◽

Cortical Surface ◽

Cortical Cells ◽

Content Type ◽

Perfusion Studies ◽

Anesthetized Dogs ◽

Fine Print

✓ Anesthetized dogs were subjected to a blow directly on the cerebral cortical surface. As measured by perfusion studies via push-pull cannulae, at the site of trauma within 20 min there was a significant increase in acetylcholine (ACh) released from the cerebral cortical cells, which rose progressively until a plateau was reached in about 1 hour. Concomitantly, ACh appeared within the cerebrospinal fluid (CSF) within 40 min after the injury. In addition, as monitored by the ACh liberation, the injured cells were apparently unable to respond functionally to a subcortical stimulus for several hours after the trauma. These studies support the hypothesis that ACh is released from the mechanically damaged cells, and then subsequently leaks into the CSF. The evidence suggests that a cholinergic factor may be significant in brain injury.

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