Extent Of Brain Edema Research Articles

Secretory meningiomas: A benign subgroup causing life-threatening complications

While meningiomas are known as slow-growing extracerebral neoplasms, the subgroup of secretory meningiomas with histologically benign characteristics tend to cause disproportional peritumoral edema, frequently leading to severe medical and neurological complications in postoperative management. Among 1,484 meningiomas that were resected at our institution between 1990 and 2007, 44 (3%) patients were found to have the histological diagnosis of a secretory meningioma. The clinical course, radiological appearance, and histopathological features were retrospectively analyzed to examine the specifics of these benign lesions. Meningiomas were located at the convexity (n = 14), the cranial base (18), and the sphenoid ridge (12). A severe, nearly hemispheric perifocal edema disproportional to tumor size was seen on preoperative MR imaging in 18 (41%) patients. Following surgical resection, the postoperative course was uneventful in 29 patients. In 15 patients, severe peritumoral edema continued or even increased on postoperative CT imaging. Six patients showed midline shift and clinical worsening necessitating respirator-assisted ventilation and intracranial pressure monitoring. An association between the extent of brain edema and number of periodic acid Schiff-positive pseudopsammomas was found (p < 0.02). Further, the size of the edema correlated with the number of immunohistochemically detected cells expressing carcinoembryonic antigen (CEA) and cytokeratin (CK) (p < 0.01). Mean MIB-1 (Ki-67 antigen) proliferation index was 3.0% (range, 0%-17%) and did not correlate with edema or tumor recurrence. Secretory meningiomas are frequently associated with severe peritumoral edema. The extent of edema correlates with immunohistochemically detected expression of CEA and CK. Extended perifocal edema in meningiomas is an unusual finding and should alert the neurosurgeon that surgery may aggravate edema excessively, leading to a life-threatening postoperative situation.

Effects of simultaneous application of ultrasound and microbubbles on intracerebral hemorrhage in an animal model

Microbubble-enhanced sonothrombolysis (MEST) may be an alternative therapeutic option in ischemic stroke. Clinical study of the efficacy of MEST as an adjunct stroke therapy, before imaging with CT or MRI, requires experimental data on the safety of this approach in the presence of hemorrhagic stroke. We, therefore, investigated the effect of diagnostic transcranial ultrasound combined with microbubbles (US + MB) in an experimental animal model of intracerebral hemorrhage (ICH). ICH was induced in anesthetized rats by intracerebral collagenase injection. Transcranial ultrasound (2 MHz, mechanical index 1.3, 1051 kPa) was applied 3 h after ICH induction to rat brains for 30 min during a continuous IV infusion of sulfur hexafluoride microbubbles (SonoVue ™). The size of cerebral hemorrhage, the extent of brain edema, and the amount of apoptosis were compared with those from control rats with ICH but without US + MB. Results showed no significant effect of US + MB on hemorrhage size (control 23.3 ± 10.7 mm 3, US + MB 20.3 ± 5.8 mm 3), on the extent of brain edema (control 3.3 ± 2.0%, US +MB 3.5 ± 1.9%), or on the rate of apoptosis (control 5.2 ± 1.5%, US + MB 5.2 ± 1.0%). We conclude that diagnostic ultrasound in combination with microbubbles does not cause additional damage to the rat brain during ICH in our experimental set-up. This finding provides support for the use of MEST as an early stroke therapy. (E-mail: meairs@neuro.ma.uni-heidelberg.de)

Diffusion-Weighted Imaging of Edema following Traumatic Brain Injury in Rats: Effects of Secondary Hypoxia

Hypoxia and edema are frequent and serious complications of traumatic brain injury (TBI). Therefore, we examined the effects of hypoxia on edema formation after moderate lateral fluid percussion (LFP) injury using NMR diffusion-weighted imaging (DWI). Adult Sprague-Dawley rats were separated into four groups: sham uninjured (S), hypoxia alone (H), trauma alone (T), and trauma and hypoxia (TH). Animals in Groups T and TH received LFP brain injury, with Groups H and TH undergoing 30 min of moderately severe hypoxia (FiO2 = 0.11) immediately after surgery or TBI (respectively). DWIs were obtained at 2, 4, and 24 h and at 1 week post injury, and apparent diffusion coefficient (ADC) maps were constructed. Animals in Groups T and TH showed an early decrease (p < 0.001) in ADC values in the cortex ipsilateral to TBI 4 hr post injury, followed by elevated ADCs 1 week later (p < 0.05). No significant differences in ADC values were seen between T and TH groups in the ipsilateral cortex. In contrast, the ipsilateral hippocampus for Group TH showed only increasing ADC values. This hyperintensity in the ADC map began at 2 h after TBI, was significant by 24 h (p < 0.05), and reached a maximum at 1 week. This hyperintensity was not observed in Group T. Histopathology seen in TBI animals corresponded well with the pathology observed with MRI. Midline shifts reflecting edema were only observed in TBI animals with little difference between normoxic (T) and hypoxic animals (TH). In sum, this study demonstrates that the development and extent of brain edema following TBI can be examined in vivo in rats using DWI technology. TBI resulted in an early decrease in ADC values indicating cytotoxic edema in the cortex that was followed at 1 week by an increase in the ADC that was associated with decreased tissue cellularity. Histopathology corresponded well to the regions of brain injury and edema visualized by T2 and DWI procedures. Overall, the addition of hypoxia to brain injury resulted in a small increase in the magnitude of edema in hippocampus and cortex over that seen with trauma alone.

External carotid artery territory ischemia impairs outcome in the endovascular filament model of middle cerebral artery occlusion in rats.

Middle cerebral artery occlusion (MCAO) by an intraluminal filament is a widely accepted animal model of focal cerebral ischemia. In this procedure, cutting of the external carotid artery (ECA) is a prerequisite for thread insertion. However, the implications of ECA transsection have not yet been described. After 90 minutes of filament MCAO or sham surgery, rats were evaluated for up to 14 days in terms of body weight development, core temperature, and motor performance. Repeated in vivo MRI of the head and neck was performed for quantification of brain edema and infarct volume. The temporal muscles were histologically analyzed postmortem. In 47% of all rats, ischemic tissue damage to the ipsilateral ECA area, including temporal, lingual, and pharyngeal musculature, was detectable by MRI. Histology of temporal muscles confirmed acute ischemic myopathy. Animals with ECA territory ischemia (ECA-I) showed delayed body weight development and poorer recovery of motor function. There was no difference in the extent of brain edema or final cerebral lesion size between ECA-I-affected and unaffected rats. Filament MCAO was complicated by the consequences of ECA ischemia in approximately half of all rats. Impaired mastication and swallowing functions restricted ingestion and resulted in postsurgical body weight loss and worse motor performance. Impaired cerebral microperfusion resulting from dehydration and reduced spontaneous motor activity resulting from reduced food and water uptake might have contributed to poorer neurological recovery in ECA ischemic rats. Thus, adverse effects caused by extracerebral ischemia with potential impact on outcome have to be considered in this stroke model.

Neuroprotection of Creatine Supplementation in Neonatal Rats with Transient Cerebral Hypoxia-Ischemia

We hypothesized that creatine (Cr) supplementation would preserve energy metabolism and thus ameliorate the energy failure and the extent of brain edema seen after severe but transient cerebral hypoxia-ischemia (HI) in the neonatal rat model. Six-day-old (P6) rats received subcutaneous Cr monohydrate injections for 3 consecutive days (3 g/kg body weight/day), followed by ³¹P-magnetic resonance spectroscopy (MRS) at P9. In a second group, P4 rats received the same Cr dose as above for 3 days prior to unilateral common carotid artery ligation followed 1 h later by 100 min of hypoxia (8% O₂) at P7. Rats were maintained at 37°C rectal temperature until magnetic resonance imaging was performed 24 h after HI. Cr supplementation for 3 days significantly increased the energy potential, i.e. the ratio of phosphocreatine to β-nucleotide triphosphate (PCr/βNTP) and PCr/inorganic phosphate (PCr/Pi) as measured by ³¹P-MRS. Rats with hemispheric cerebral hypoxic-ischemic insult that had received Cr showed a significant reduction (25%) of the volume of edemic brain tissue compared with controls as calculated from diffusion-weighted images (DWI). Thus, prophylactic Cr supplementation demonstrated a significant neuroprotective effect 24 h after transient cerebral HI. We hypothesize that neuroprotection is probably due to the availability of a larger metabolic substrate pool leading to a reduction of the secondary energy failure because DWI has been reported to correlate with the PCr/Pi ratio in the acute phase of injury. Additional protection by Cr may be related to prevention of calcium overload, prevention of mitochondrial permeability transition pore opening and direct antioxidant effects.

Effects of hypothermia and rewarming on evoked potentials during transient focal cerebral ischemia in cats

We examined the effects of mild to moderate hypothermia and the influence of rewarming on electrophysiological function using somatosensory evoked potentials (SEPs) in transient focal ischemia in the brain. Nineteen cats underwent 60 min of left middle cerebral artery occlusion under normothermic (36 ° -37 ° C, n = 6) or hypothermic (30 ° -31 ° C, n = 13) conditions followed by 300 min of reperfusion with slow (120 min, n = 6) or rapid (30 min, n = 7) rewarming. Whole-body hypothermia was induced during ischemia and the first 180 min of reperfusion. SEPs and regional cerebral blood flow were measured before and during ischemia and during reperfusion. The specific gravity of gray and white matter was examined as the indicator of edema. During rewarming, SEP amplitudes recovered gradually. After rewarming, SEPs in the normothermic and rapid rewarming groups remained depressed (20%-40% of pre-occlusion values); however, recovery of SEPs was significantly enhanced in the slow rewarming group (p < 0.05). Hypothermia followed by slow rewarming reduced edema in gray and white matter. Rapid rewarming did not reduce edema in the white matter. The recovery of SEPs correlated with the extent of brain edema in transient focal ischemia. Rapid rewarming reduced the protective effect of hypothermia. [Neurol Res 2002; 24: 621-626]

A novel brain trauma model in the mouse: effects of dexamethasone treatment.

We describe a novel methodological approach for inducing cold lesion in the mouse as a model of human cortical contusion trauma. To validate its reproducibility and reliability, dexamethasone (Dxm) was repeatedly applied to demonstrate possible antioedematous drug effects. Following the induction of anaesthesia with halothane, the dura was exposed via trephination. Using a micromanipulator a pre-cooled (-78 degrees C) copper cylinder, 3 mm in diameter, was pressed down to a depth of 1 mm onto the dura for 30 s under microscopic control. The body temperature was held constant at 37 degrees C throughout the procedure. Blood pressure (BP), measured by a modified photosensor-monitored tail-cuff method, and acid-base status were not significantly different when analysed before and after cold lesion and prior to sacrifice. However, there was a marginal mixed respiratory and metabolic acidosis. The antioedematous action of Dxm was studied in four standard pre-and post-treatment paradigms: 2x0.5 mg/kg (II), 2x12.5 mg/kg (III) and 4x6.25 mg/kg (IV: 3x pre-, 1x post-treatment: V: 1x pre-, 3x post-treatment). Physiological saline injections served as controls. High doses of Dxm (III-V) significantly attenuated the cold-lesion-induced loss of body mass. Dxm treatment also resulted in a reduction of brain water content (III; P<0.05), and brain swelling (IV; P<0.05) in the lesioned hemisphere, relative to controls. In conclusion, we have characterized a novel cold lesion model in the mouse to mimic traumatic brain injury and the beneficial effect of Dxm treatment on the extent of brain oedema.

Lack of protection from ischemic injury of monoamine oxidase B-deficient mice following middle cerebral artery occlusion

Adult male wild-type mice received intraperitoneal (i.p.) administration of saline ( n=9) or 10 mg/kg L-deprenyl ( n=9) three times a week for 3 weeks. Mice with targeted inactivation of the monoamine oxidase B (MAO-B) gene received i.p. administration of saline ( n=8). Animals underwent ligation of the left common and external carotid arteries, followed by cauterization of the ipsilateral middle cerebral artery. Twenty-four hours post-surgery, all groups showed right torsion of the torso but no evidence of limb weakness, lateral instability, or circling. Ischemic changes were assessed from digitized video-images of serial sections of the brain stained with Hematoxylin/Eosin. No significant group differences were detected in infarct volume (14–18% of ipsilateral cortex) or in the extent of brain edema (4–7% increase in ipsilateral hemispheric swelling with respect to contralateral side). Our results suggest that absence of the MAO-B gene or inhibition of the enzyme with L-deprenyl are not protective or detrimental in an animal model of acute cortical infarction.

MIB-1 staining index and peritumoral brain edema of meningiomas

Growth rates and tumor aggressiveness of meningiomas are thought to be closely related to brain edema development. However, histopathologic data alone are not consistently accurate predictors of the behavior and clinical course of a meningioma. The authors examined 57 histologically proven intracranial meningiomas to identify factors, including growth fractions determined by MIB-1 immunostaining, that may influence the development of meningioma-associated peritumoral brain edema. There were 54 benign, 2 atypical, and 1 anaplastic meningiomas. The MIB-1 staining index (SI) percentage was defined as the number of MIB-1 positive cells divided by the total number of tumor cells in a 1.037-square millimeter area on the slide. The extent of peritumoral brain edema was determined using preoperative magnetic resonance imaging. The extent of edema was classified as Grade 0,1, or 2 (GR0, GR1, or GR2), in order of increasing severity. The MIB-1 SIs of the 57 cases ranged from 0.06-6.8% (median, 0.80%). There were 26 GR0, 20 GR1, and 11 GR2 edema cases. The MIB-1 SI rose in order of increasing edema severity. There was a statistically significant correlation between the MIB-1 SI and the extent of brain edema (P<0.0001), and also between the tumor size and the extent of brain edema (P=0.001). Meningothelial and atypical/anaplastic meningiomas were associated with peritumoral brain edema more often than any other subtype (P<0.005). Growth fractions, as determined by MIB-1 immunostaining, rise with increasing severity of peritumoral brain edema, indicating a close relationship between tumor aggressiveness and edema development.

Intracerebral infusion of thrombin as a cause of brain edema.

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 microliters 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/microliter resulted in a significant increase in brain water content. Rats receiving 10 U/microliters 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/microliters. Edema formation was prevented by another highly specific thrombin inhibitor, N alpha-(2-Naphthalenesulfonylglycyl)-4-DL-phenylalaninepiperidid e (alpha-NAPAP). Thrombin-induced 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 alpha-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/microliter, an amount within the range of concentrations used for topical hemostasis in neurosurgery.

Oedema reduction by levemopamil in focal cerebral ischaemia of spontaneously hypertensive rats studied by magnetic resonance imaging

The effect of treatment with the Ca 2+ channel blocker and 5-HT 2 receptor antagonist levemopamil (recommended INN for ( S)-emopamil) on the extent of ischaemic brain oedema was studied by magnetic resonance imaging in vivo. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent middle cerebral artery occlusion. The treatment consisted of slow intravenous injections of an aqueous solution of levemopamil given immediately after middle cerebral artery occlusion and again 2 h and 4 h later. One group of animals ( n = 17) received 3 × 2 mg/kg of levemopamil (total dose: 6 mg/kg) and another group ( n = 13) received 3 × 4 mg/kg (total dose: 12 mg/kg). Saline was administered to the controls ( n =16) at corresponding times. High-resolution T 2-weighted spin echo images were obtained 24 h after middle cerebral artery occlusion from two transversal brain planes (4.5 mm and 6.5 mm dorsal to the interaural line). Dose-dependent reductions of brain oedema were achieved in both brain planes. The lower dose of levemopamil reduced the extent of oedema significantly ( P < 0.05) by 20 ± 3.7% in the upper and by 21 ± 3.8% in the lower brain plane as compared to the controls (means ± S.E.M.). The higher dose diminished the extent of oedema in the same planes by 30 ± 3.5% and 31 ± 4.0%, respectively. Dose-dependent reductions of infarct size, as determined by vital tissue staining using 2,3,5-triphenyltetrazolium chloride (TTC), were observed in the levemopamil-treated groups. Body temperature was not affected by levemopamil, suggesting direct cerebroprotection by this drug. The results of this magnetic resonance imaging study indicate that the extent of brain oedema and infarction is dose dependently reduced by treatment with levemopamil in a clinically relevant stroke model.

Combined treatment with nicardipine, phenobarbital, and methylprednisolone ameliorates vasogenic brain edema.

Free radicals formed around the edematous areas of the brain can cause lipoperoxidation of the cellular membrane, followed by calcium influx into the cell through calcium channels. These secondary insults may aggravate vasogenic brain edema. Since phenobarbital is a free radical scavenger, methylprednisolone has an antilipoperoxidation effect; and nicardipine is a calcium channel blocker, we hypothesized that combined treatment with phenobarbital, methylprednisolone, and nicardipine would be beneficial in vasogenic brain edema. This hypothesis was tested in Sprague-Dawley rats with a transdural cold-injury on the right parietal cortex. The animals were randomly divided into two groups. Animals in the treatment group were injected intraperitoneally with phenobarbital (4 mg/kg), methylprednisolone (50 mg/kg), and nicardipine (10 micrograms/kg) at 5 min and 8 hours after the cold-injury. The control animals were injected with saline. These animals were sacrificed 24 hours after the injury. The extent of brain edema was assessed by measuring the water content, the inulin distribution volume, and the distribution area of Evans blue in the brain. Our results showed that the water content of the edematous hemisphere was similar in the control and the treatment groups. However, Evans blue distribution area and inulin distribution volume of the treatment group were less than those of the control group by 12% and 31%, respectively. In conclusion, the combined treatment with phenobarbital, methylprednisolone and nicardipine is beneficial in vasogenic brain edema.

Cerebroprotective effect of dexamethasone by increasing the tolerance to hypoxia and preventing brain oedema in newborn piglets with experimental pneumothorax

The effect of dexamethasone (DXM) pretreatment in newborn piglets with experimental pneumothorax (EPT) was studied. Neither low DXM doses nor those administered 1 or 2 h prior to the induction of EPT were found to be effective against its course. In contrast, 5 mg/kg of body wt. of DXM given subcutaneously 4 h prior to EPT improved significantly both the tolerance and laboratory data of the animals. The extent of brain oedema, measured 4 h after recovery, was also considerably lowered. Actinomycin D pretreatment prevented almost completely the beneficial effect offered by DXM suggesting the involvement of newly synthesized protein(s) in the cerebroprotective effect of DXM.