Search

Background: An external ventricular drain (EVD) is used to measure intracranial pressure (ICP) and to drain cerebrospinal fluid (CSF). The procedure is generally safe, but parenchymal sequelae are reported as a possible side effect, with variable incidence. We investigated the mechanical sequelae of EVD insertion and their clinical significance in acute brain-injured patients, with a special focus on hemorrhagic lesions. Methods: Mechanical sequelae of EVD insertion were detected in patients by computed tomography (CT) and magnetic resonance imaging (MRI), performed for clinical purposes. Results: In 155 patients we studied the brain tissue surrounding the EVD by CT scan (all patients) and MRI (16 patients); 53 patients were studied at three time points (day 1-2, day 3-10, >10 days after EVD placement) to document the lesion time course. Small hemorrhages, with a hyperdense core surrounded by a hypodense area, were identified by CT scan in 33 patients. The initial average (hyper- + hypodense) lesion volume was 8.16 ml, increasing up to 15 ml by >10 days after EVD insertion. These lesions were not accompanied by neurologic deterioration or ICP elevation. History of arterial hypertension, coagulation abnormalities and multiple EVD insertions were significantly associated with hemorrhages. In 122 non-hemorrhagic patients, we detected very small hypodense areas (average volume 0.38 ml) surrounding the catheter. At later times these hypodensities slightly increased. MRI studies in 16 patients identified both intra- and extracellular edema around the catheters. The extracellular component increased with time. Conclusion: EVD insertion, even when there are no clinically important complications, causes a tissue reaction with minimal bleedings and small areas of brain edema. [ABSTRACT FROM AUTHOR]

Hemorrhagic stroke, accounting for 10-30% of stroke cases, carries high rates of morbidity and mortality. This review presents the current knowledge on the efficacy of hyperbaric oxygen (HBO)-based modalities in the preclinical research on hemorrhagic stroke. Both preconditioning and post-treatment with HBO are considered as prospective therapeutic options. High efficacy of HBO therapy (HBOT) for brain hemorrhage has been noted. We found that moderate hyperbaric pressures appear optimal for therapeutic effect, while the therapeutic window of opportunity is short. HBO preconditioning offers more modest neuroprotective benefit as compared to HBO post-treatment for experimental intracerebral hemorrhage. We advocate for mandatory calculations of percent changes in the experimentally investigated indexes of HBO effectiveness and stress the need to design new clinical trials on HBO for hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Microglia are the first responders to intracerebral hemorrhage, but their precise role in intracerebral hemorrhage remains to be defined. Microglia are the only type of brain cells expressing the colony-stimulating factor 1 receptor, a key regulator for myeloid lineage cells. Here, we determined the effects of a colony-stimulating factor 1 receptor inhibitor (PLX3397) on microglia and the outcome in the context of experimental mouse intracerebral hemorrhage. We show that PLX3397 effectively depleted microglia, and the depletion of microglia was sustained after intracerebral hemorrhage. Importantly, colony-stimulating factor 1 receptor inhibition attenuated neurodeficits and brain edema in two experimental models of intracerebral hemorrhage induced by injection of collagenase or autologous blood. The benefit of colony-stimulating factor 1 receptor inhibition was associated with reduced leukocyte infiltration in the brain and improved blood-brain barrier integrity after intracerebral hemorrhage, and each observation was independent of lesion size or hematoma volume. These results demonstrate that suppression of colony-stimulating factor 1 receptor signaling ablates microglia and confers protection after intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate to which degree the peritumoral brain edema in patients with meningiomas depends on aquaporin-4 (AQP4) expression, tumor grade, tumor volume, Ki-67 expression, and cell count.Procedures: Thirty-three patients (25 women, 8 men; mean age 56.6 ± 16.0 years) with an intracranial meningioma underwent a standardized magnetic resonance (MR) examination prior to surgical resection. Edema indices (EIs) and tumor volumes were measured on the MR images. Tumor grade was classified according to the World Health Organization, and the proliferation index was estimated on Ki-67 antigen-stained specimens. Tumor cell count was evaluated. Eighteen specimens were stained for AQP4 expressioon.Results: Significant intergroup differences between AQP4 expression grades and EIs were observed (P = 0.03), and a positive correlation was detected between EIs and AQP4 expression grades (r = 0.54; P < 0.05). A ROC analysis with EI as a test variable revealed an AUC of 0.77 (95 % CI 0.55-0.99) for the prediction of a moderate-to-strong AQP4 expression. An EI ≥1.5 predicted a moderate-to-high AQP4 expression with a sensitivity of 77 % and a specificity of 60 %. EI values of 2.2 and 3.5 reached sensitivity/specificity values of 69/80 % and 54/100 %, respectively. The AQP4 expression did not show any significant correlations with tumor grading, tumor volume, Ki-67 expression, or cell count. Moreover, we observed no significant positive or negative correlations between the EI and tumor grading (P = 0.7), tumor volume (P = 0.19), Ki-67 index (P = 0.9), and cell count (P = 0.34).Conclusion: Peritumoral brain edema in patients with meningiomas may depend on AQP4 expression grades and not on tumor grade, tumor volume, Ki-67 expression, and cell count. The amount of edema predicted AQP4 expressions with moderate-to-good sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Effects of ammonia on astrocytes play a major role in hepatic encephalopathy, acute liver failure and other diseases caused by increased arterial ammonia concentrations (e.g., inborn errors of metabolism, drug or mushroom poisoning). There is a direct correlation between arterial ammonia concentration, brain ammonia level and disease severity. However, the pathophysiology of hyperammonemic diseases is disputed. One long recognized factor is that increased brain ammonia triggers its own detoxification by glutamine formation from glutamate. This is an astrocytic process due to the selective expression of the glutamine synthetase in astrocytes. A possible deleterious effect of the resulting increase in glutamine concentration has repeatedly been discussed and is supported by improvement of some pathologic effects by GS inhibition. However, this procedure also inhibits a large part of astrocytic energy metabolism and may prevent astrocytes from responding to pathogenic factors. A decrease of the already low glutamate concentration in astrocytes due to increased synthesis of glutamine inhibits the malate-aspartate shuttle and energy metabolism. A more recently described pathogenic factor is the resemblance between NH and K in their effects on the Na,K-ATPase and the Na,K, 2 Cl and water transporter NKCC1. Stimulation of the Na,K-ATPase driven NKCC1 in both astrocytes and endothelial cells is essential for the development of brain edema. Na,K-ATPase stimulation also activates production of endogenous ouabains. This leads to oxidative and nitrosative damage and sensitizes NKCC1. Administration of ouabain antagonists may accordingly have therapeutic potential in hyperammonemic diseases. [ABSTRACT FROM AUTHOR]

A 71‐year‐old man had disordered consciousness whose Glasgow Coma Scale was E4V1M5. His blood pressure was high, but there was no abnormality in the cerebrospinal fluid examination. The MRI finding reveals a high‐intensity area at the pons without the blood flow interruption. Thus, he has diagnosed with brainstem PRES. [ABSTRACT FROM AUTHOR]

The prevention of BBB breakdown and the subsequent vasogenic edema are important parts of the medical management of ischemic stroke. The purpose of this study was to investigate the ischemic tolerance effect of Rosmarinus officinalis leaf hydro-alcoholic extract (RHE). Five groups of animals were designed: sham (underwent surgery without MCAO) and MCAO groups, the MCAO groups were pretreated orally by gavages with RHE (50, 75, and 100 mg/Kg/day), daily for 30 days. Two hours after the last dose, serum lipid levels were determined and then the rats were subjected to 60 min of middle cerebral artery occlusion followed by 24 h of reperfusion. Subsequently, brain infarct size, brain edema and Evans Blue dye extravasations were measured and neurological deficits were scored. Dietary RHE could significantly reduce cortical and sub-cortical infarct volumes (211.55 ± 24.88 mm³ vs. 40.59 ± 10.04 mm³ vs. 29.96 ± 12.19 mm³vs. 6.58 ± 3.2 mm³), neurologic deficit scores, cerebral edema (82.34 ± 0.42% vs. 79.92 ± 0.49% vs. 79.45 ± 0.26% vs. 79.30 ± 0.19%), blood-brain barrier (BBB) permeability (7.73 ± 0.4 μg/g tissue vs. 4.1 ± 0.23 μg/g tissue vs. 3.58 ± 0.3 μg/g tissue vs. 3.38 ± 0.25 μg/g tissue) in doses of 50, 75 and 100 mg/Kg/day as compared with the control group in the transient model of focal cerebral ischemia. Although pretreatment with RHE plays an important role in the generation of tolerance against cerebral I/R injury, further studies are needed to clarify the mechanism of the ischemic tolerance. [ABSTRACT FROM AUTHOR]

Purpose: High-velocity trauma with acceleration/deceleration forces turns into shear stress over lenticulostriate or anterior choroidal arteries that lead to basal ganglia hemorrhage. Traumatic basal ganglia hematoma has rarely been described in pediatric population. The aim of this study was to present our clinical series of pediatric patients with traumatic basal ganglia hematoma and to analyze the prognostic indicators of traumatic basal ganglia hematoma. Methods: In this retrospective case series, emergency admissions of pediatric patients with traumatic basal ganglia hematoma due to closed head injury were analyzed. Demographic, clinical, and radiographical data of the patients were retrieved from patients' charts and picture archiving and communication system. Results: There were four children with traumatic basal ganglia hematoma (TBGH). All patients were male. Median age was 8 years (range = 7-16 years). Road accident (three) and fall (one) were the causes of the traumas. Basal ganglia hematoma was present on the right side in one patient and on the left side in three patients. Hematoma volumes ranged from 0.9 to 8.94 ml. All patients were treated conservatively. One patient recovered fully; two patients were moderately disabled at their last clinical follow-ups. The last patient with diffuse subarachnoidal hemorrhage and edema died despite all interventions. Conclusions: Traumatic basal ganglia hematomas are unique and different from other kind of intracerebral hematomas. The eloquent nature of basal ganglia makes it more vulnerable to head trauma. Mechanism of injury, energy and velocity of injury are the most important prognostic criteria. Post-traumatic phase of injury should be carefully observed in patients with TBGH, especially when mechanism and velocity of injury are severe and high. [ABSTRACT FROM AUTHOR]

Numerous preclinical studies indicate that sustained endothelial activation significantly contributes to tissue edema, perpetuates the inflammatory response, and exacerbates tissue injury ultimately resulting in organ failure. However, no specific therapies aimed at restoring endothelial function are available as yet. Sphingosine-1-phosphate (S1P) is emerging as a potent modulator of endothelial function and endothelial responses to injury. Recent studies indicate that S1PR are attractive targets to treat not only disorders of the arterial endothelium but also microvascular dysfunction caused by ischemic or inflammatory injury. In this article, we will review the current knowledge of the role of S1P and its receptors in endothelial function in health and disease, and we will discuss the therapeutic potential of targeting S1PR not only for disorders of the arterial endothelium but also the microvasculature. The therapeutic targeting of S1PR in the endothelium could help to bridge the gap between biomedical research in vascular biology and clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of minimally invasive hematoma aspiration (MIHA) on the c-Jun NH2-terminal kinase (JNK) signal transduction pathway after intracerebral hemorrhage (ICH). Methods: In this experiment, 300 adult male Wistar rats were randomly and averagely divided into sham-operated group, ICH group and MIHA group. In each group, 60 rats were used in the detection of indexes in this experiment, while the other 40 rats were used to replace rats which reached the exclusion criteria (accidental death or operation failure). In ICH group and MIHA group, ICH was induced by injection of 70 'L of autologous arterial blood into rat brain, while only the rats in MIHA group were treated by MIHA 6 h after ICH. Rats in sham-operated group were injected nothing into brains, and they were not treated either, like rats in ICH group. In each group, six rats were randomly selected to observe their Bederson's scales persistently (6, 24, 48, 72, 96, 120 h after ICH). According to the time they were sacrificed, the remaining rats in each group were divided into 3 subgroups (24, 72, 120 h). The change of brain water content (BWC) was measured by the wet weight to dry weight ratio method. The morphology of neurons in cortex was observed by the hematoxylin-eosin (HE) staining. The expressions of phospho-c-Jun NH2-terminal kinase (pJNK) and JNK in peri-hematomal brain tissue were determined by the immunohistochemistry (IHC) and Western blotting (WB). Results: At all time points, compared with the ICH groups, the expression of pJNK decreased obviously in MIHA groups (p < 0.05), while their Bederson's scales and BWC declined, and neuron injury in the cortex was relieved. The expression level of JNK was not altered at different groups. The data obtained by IHC and WB indicated a high-level of consistency, which provided a certain dependability of the test results. Conclusion: The JNK signal transduction pathway could be activated after intracerebral hemorrhage, with the expressions of pJNK increasing. MIHA could relieve the histo-pathological damage of nerve cells, reducing brain edema and neurological deficits, and these neuroprotective effects might be associated with suppression of JNK signal transduction pathway. [ABSTRACT FROM AUTHOR]

The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability. [ABSTRACT FROM AUTHOR]

Cefazolin is commonly administered before surgery as a prophylactic antibiotic. Hypersensitivity to cefazolin is not uncommon, and the symptoms mostly include urticaria, skin reaction, diarrhea, vomiting, and transient neutropenia, which are rarely life threatening. We present a rare case of fatal cefazolin hypersensitivity in a female who was diagnosed with multiple meningiomas and scheduled for craniotomy and tumor removal. Immediately after cefazolin IV administration, the patient developed acute hypertensive crisis, which resolved within 10 minutes after the treatment. This was followed by unexplained metabolic acidosis. The patient then developed severe brain edema 100 minutes later. The patient had facial edema when her face was exposed for the next 30 minutes. A computed tomography scan revealed global brain edema with herniation. She was admitted to the intensive care unit for symptomatic treatment and died 10 days after surgery from multiorgan failure. The serum IgE level was very high (734 IU/mL). Single-dose administration of cefazolin for surgical prophylaxis may lead to rare, fatal adverse reaction. The warning signs are sudden, unexplained metabolic acidosis, hypertensive crisis, tachycardia, and facial angioedema predominating with or without cutaneous symptoms like urticaria. [ABSTRACT FROM AUTHOR]

Military personnel are often subjected to sleep deprivation (SD) during combat operations. Since SD is a severe stress and alters neurochemical metabolism in the brain, a possibility exists that acute or long-term SD will influence blood-brain barrier (BBB) function and brain pathology. This hypothesis was examined in young adult rats (age 12 to 14 weeks) using an inverted flowerpot model. Rats were placed over an inverted flowerpot platform (6.5 cm diameter) in a water pool where the water levels are just 3 cm below the surface. In this model, animals can go to sleep for brief periods but cannot achieve deep sleep as they would fall into water and thus experience sleep interruption. These animals showed leakage of Evans blue in the cerebellum, hippocampus, caudate nucleus, parietal, temporal, occipital, cingulate cerebral cortices, and brain stem. The ventricular walls of the lateral and fourth ventricles were also stained blue, indicating disruption of the BBB and the blood-cerebrospinal fluid barrier (BCSFB). Breakdown of the BBB or the BCSFB fluid barrier was progressive in nature from 12 to 48 h but no apparent differences in BBB leakage were seen between 48 and 72 h of SD. Interestingly, rats treated with metal nanoparticles, e.g., Cu or Ag, showed profound exacerbation of BBB disruption by 1.5- to 4-fold, depending on the duration of SD. Measurement of plasma and brain serotonin showed a close correlation between BBB disruption and the amine level. Repeated treatment with the serotonin 5-HT receptor antagonist ondansetron (1 mg/kg, s.c.) 4 and 8 h after SD markedly reduced BBB disruption and brain pathology after 12 to 24 h SD but not following 48 or 72 h after SD. However, TiO2-nanowired ondansetron (1 mg/kg, s.c) in an identical manner induced neuroprotection in rats following 48 or 72 h SD. However, plasma and serotonin levels were not affected by ondansetron treatment. Taken together, our observations are the first to show that (i) SD could induce BBB disruption and brain pathology, (ii) nanoparticles exacerbate SD-induced brain damage, and (iii) serotonin 5-HT3 receptor antagonist ondansetron is neuroprotective in SD that is further potentiated byTiO2-nanowired delivery, not reported earlier. [ABSTRACT FROM AUTHOR]

Neuroinflammation plays an important role in the pathophysiology of surgical brain injury (SBI). Phosphoinositide 3-kinase gamma (PI3Kγ), predominately expressed in immune and endothelial cells, activates multiple inflammatory responses. In the present study, we investigated the role of PI3Kγ and PI3Kγ-activated phosphodiesterase 3B (PDE3B) in neuroinflammation in a rat model of SBI. One hundred and fifty-two male Sprague Dawley rats (weight 280 -350 g) were subjected to a partial right frontal lobe corticotomy model of SBI. A PI3Kγ pharmacological inhibitor (AS252424 or AS605240) was administered intraperitoneally. PI3Kγ siRNA, human recombinant active-PI3Kγ protein, or human recombinant active-PDE3B protein were administered intracerebroventricularly. Post-SBI assessments included neurobehavioral tests, brain water content, Western blot, and immunohistochemistry. Endogenous PI3Kγ levels were increased within peri-resection brain tissues after SBI, accompanied by increased brain water content and neurological functional deficits. There was a trend toward increased endogenous PDE3B phosphorylation after SBI. The selective PI3Kγ inhibitors AS252424 and AS605240 reduced brain water content surrounding corticotomy and improved neurological function after SBI. SBI increased and PI3Kγ inhibitor decreased levels of myeloperoxidase, cluster of differentiation 3, mast cell degranulation, E-selectin, and IL-1 in peri-resection brain tissues. Direct administration of human recombinant active-PI3Kγ protein and active-PDE3B protein countered the protective effect of AS252424. PI3Kγ siRNA reduced PI3Kγ levels, decreased brain water content within peri-resection brain tissues, and improved neurological function after SBI. Collectively, our findings suggest that PI3Kγ contributed to neuroinflammation after SBI. The use of selective PI3Kγ inhibitors may be a novel approach to ameliorating SBI via their anti-inflammation effects. [ABSTRACT FROM AUTHOR]

Previous studies have shown that patients with hepatitis B virus-related cirrhosis (HBVRC) without overt hepatic encephalopathy (OHE) are associated with a varying degree of cognitive dysfunction. Several resting-state functional magnetic resonance imaging (fMRI) studies have been conducted to explore the neural correlates of such cognitive deficits, whereas little effort has been made to investigate the cortical integrity in cirrhotic patients without OHE. Here, using cortical thickness, surface area and local gyrification index (lGI), this study performed a comprehensive analysis on the cortical morphometry of patients with HBV-RC without OHE (HBV-RC-NOHE) vs. matched healthy controls. Compared with healthy controls, we found significantly increased cortical thickness in the bilateral lingual and parahippocampal gyrus, right posterior cingulate cortex, precuneus, peri-calcarine sulcus and fusiform gyrus in patient with HBV-RC-NOHE, which may closely relate to be the low-grade brain edema. Cortical gyrification analysis showed significantly increased lGI in the left superior and inferior parietal cortex as well as lateral occipital cortex, which was speculated to be associated with disruptions in white matter connectivity and sub-optimal intra-cortical organization. In addition, the mean cortical thickness/lGI of the regions with structural abnormalities was shown to be negatively correlated with psychometric hepatic encephalopathy score (PHES) of the patients with HBV-RC-NOHE. These morphological changes may serve as potential markers for the preclinical diagnosis and progression of HBV-RC-NOHE. [ABSTRACT FROM AUTHOR]

Megalencephalic leukoencephalopathy with subcortical cysts (MLCs) disease is a rare inherited, autosomal recessive form of childhood-onset spongiform leukodystrophy characterized by macrocephaly, deterioration of motor functions, epileptic seizures and mental decline. Brain edema, subcortical fluid cysts, myelin and astrocyte vacuolation are the histopathological hallmarks of MLC. Mutations in either the MLC1 gene (>75% of patients) or the GlialCAM gene (<20% of patients) are responsible for the disease. Recently, the GlialCAM adhesion protein was found essential for the membrane expression and function of the chloride channel ClC-2 indicating MLC disease caused by mutation in GlialCAM as the first channelopathy among leukodystrophies. On the contrary, the function of MLC1 protein, which binds GlialCAM, its functional relationship with ClC-2 and the molecular mechanisms underlying MLC1 mutationinduced functional defects are not fully understood yet. The human MLC1 gene encodes a 377-amino acid membrane protein with eight predicted transmembrane domains which shows very low homology with voltage-dependent potassium (K+) channel subunits. The high expression of MLC1 in brain astrocytes contacting blood vessels and meninges and brain alterations observed in MLC patients have led to hypothesize a role for MLC1 in the regulation of ion and water homeostasis. Recent studies have shown that MLC1 establishes structural and/or functional interactions with several ion/water channels and transporters and ion channel accessory proteins, and that these interactions are affected by MLC1 mutations causing MLC. Here, we review data on MLC1 functional properties obtained in in vitro and in vivo models and discuss evidence linking the effects of MLC1 mutations to brain channelopathies. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a principal disease lead to death or leave behind the physical and psychological sequel. Stroke patients are increasing every year world widely. In Korea, large portion of stroke patients prefer to rely on the therapy of Korean medicine. Several transcriptions including Woohwangchungsim Won and Sohaphwang Won have been used to treat the acute stroke patients. However, it is currently difficult to have chances to treat patients. It might be partially come from the lack of scientific or statistical analysis of data of the cases. Thus, it is necessary to demonstrate the pharmacological activities on acute stage of stroke, to accumulate the case data and to analyze via basic and clinical studies. We initiated the current review with our opinions, the prescriptions used in acute stroke might be closely related to or useful in treatment of brain edema followed by the elevation of intracranial pressure (ICP), Because the symptoms in ICP elevation in acute stroke may be correlated to the indications of the prescriptions. Vasogenic edema, a major deleterious type of brain edema occurs in acute phase of stroke and persists for several days. It is known to be caused by the factors related to Blood brain barrier damage which are extensively studied. The purpose of the current study was to suggest several targets to the studies using prescriptions for acute stroke in traditional Korean Medicine. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) remains the leading cause of injury-related death and disability. Brain edema, one of the most major complications of TBI, contributes to elevated intracranial pressure, and poor prognosis following TBI. The objective of this study was to evaluate whether Ulinastatin (UTI), a serine protease inhibitor, attenuates brain edema following TBI. Our results showed that treatment with UTI at a dose of 50,000 U/kg attenuated the brain edema, as assayed by water content 24 h after TBI induction. This attenuation was associated with a significant decrease of the expression level of aquaporin-4. In addition, we showed that UTI treatment also markedly inhibited the expression of pro-inflammatory cytokines including IL-1β and TNF-α as well as activity of NF-κB. Collectively, our findings suggested that UTI may be a promising strategy to treat brain edema following TBI. [ABSTRACT FROM AUTHOR]

This case report deals with multiple intracranial metastatic tumors and studies of expression and regulation characteristics of aquaporins (AQPs) of cerebellar metastatic tumor and brain tissue surrounding tumor. In this work, we try to understand the role of abnormal expression of AQPs in formation and elimination of brain edema and provide new ideas for the treatment of brain edema induced by tumor. The work involves resection of intracranial occupying lesions to get cerebellar metastatic tumor organization. Total RNA was extracted, RT-PCR was done, and immunohistochemical staining was done to study the expression and regulation characteristics of AQPs. We found that AQP4 had a high expression in the peritumoral brain tissue and no expression in the center of brain metastasis tumor organization. Around the tumor tissue, the AQP4 staining was junior in the more distant region from tumor and it added significantly in close to the tumor tissue region. It demonstrated that the AQP4 expression was upregulated, obviously with the distance drawing near gradually to tumor tissue. In addition, stained AQP1 was not observed on cerebellar metastatic tumor and peritumoral brain microvascular endothelial cells. The phenomenon that AQP4 had an increased expression in the surrounding region of cerebellar metastatic tumor and, moreover, increased significantly in the region next to the cerebellar metastatic tumor tightly is probably related to the formation of peritumoral brain edema and plays an important role in cytotoxic brain edema mechanism. AQP1 was not expressed on cerebellar metastatic tumor and peritumoral brain tissue microvascular endothelial cells, and this may be an important factor that the peritumoral interstitial brain edema is removed ineffectively to cause 'small tumor, big edema.' [ABSTRACT FROM AUTHOR]

Objective(s): Estrogen (E2) has neuroprotective effects on blood-brain-barrier (BBB) after traumatic brain injury (TBI). In order to investigate the roles of estrogen receptors (ERs) in these effects, ER-α antagonist (MPP) and, ER-β antagonist (PHTPP), or non-selective estrogen receptors antagonist (ICI 182780) were administered. Materials and Methods: Ovariectomized rats were divided into 10 groups, as follows: Sham, TBI, E2, oil, MPP+E2, PHTPP+E2, MPP+PHTPP+E2, ICI+E2, MPP, and DMSO. E2 (33.3 μg/Kg) or oil were administered 30 min after TBI. 1 dose (150 μg/Kg) of each of MPP, PHTPP, and (4 mg/kg) ICI182780 was injected two times, 24 hr apart, before TBI and estrogen treatment. BBB disruption (Evans blue content) and brain edema (brain water content) evaluated 5 hr and 24 hr after the TBI were evaluated, respectively. Results: The results showed that E2 reduced brain edema after TBI compared to vehicle (P<0.01). The brain edema in the MPP+E2 and PHTPP+E2 groups decreased compared to the vehicle (P<0.001). There was no significant difference in MPP+PHTPP+E2 and ICI+E2 compared to TBI. This parameter in MPP was similar to vehicle. Evans blue content in E2 group was lower than vehicle (P<0.05).The inhibitory effect of E2 on Evans blue was not reduced by MPP+E2 and PHTPP+E2 groups, but decreased by treatment with MPP+PHTPP or ICI. MPP had no effect on Evans blue content. Conclusion: A combined administration of MPP and PHTPP or ICI inhibited the E2-induced decrease in brain edema and BBB disruption; this may suggest that these effects were mediated via both receptors. [ABSTRACT FROM AUTHOR]

The management of patients with large territory ischemic strokes and the subsequent development of malignant brain edema and increased intracranial pressure is a significant challenge in modern neurology and neurocritical care. These patients are at high risk of subsequent neurologic decline and are best cared for in an intensive care unit or a comprehensive stroke center with access to neurosurgical support. Risks include hemorrhagic conversion, herniation, poor functional outcome, and death. This review discusses recent advances in understanding the pathophysiology of edema formation, identifying patients at risk, current management strategies, and emerging therapies. [ABSTRACT FROM AUTHOR]

Brain edema and associated increase in intracranial pressure continue to be lethal complications of acute liver failure (ALF). Abundant evidence suggests that the edema in ALF is largely cytotoxic brought about by swelling of astrocytes. Elevated blood and brain ammonia levels have been strongly implicated in the development of the brain edema. Additionally, inflammation and sepsis have been shown to contribute to the astrocyte swelling/brain edema in the setting of ALF. We posit that ammonia initiates a number of signaling events, including oxidative/nitrative stress (ONS), the mitochondrial permeability transition (mPT), activation of the transcription factor (NF-κB) and signaling kinases, all of which have been shown to contribute to the mechanism of astrocyte swelling. All of these factors also impact ion-transporters, including Na, K, Cl cotransporter and the sulfonylurea receptor 1, as well as the water channel protein aquaporin-4 resulting in a perturbation of cellular ion and water homeostasis, ultimately resulting in astrocyte swelling/brain edema. All of these events are also potentiated by inflammation. This article reviews contemporary knowledge regarding mechanisms of astrocyte swelling/brain edema formation which hopefully will facilitate the identification of therapeutic targets capable of mitigating the brain edema associated with ALF. [ABSTRACT FROM AUTHOR]

Drinking is a risk factor for traumatic brain injury (TBI), and ethanol can aggravate the outcome by promoting brain edema. The mechanism involved is not fully understood. It has been confirmed that aquaporin-4 (AQP4) and vascular endothelial growth factor (VEGF) play pivotal roles in cytotoxic/vasogenic brain edema individually, and both of these proteins are downstream regulatory factors of hypoxia-inducible factor-1α (HIF-1α). In this study, we used a fluid percussion injury (FPI) model in rats to determine the effects of acute ethanol intake on the expression levels of HIF-1α, AQP4, and VEGF prior to FPI. The animals were sacrificed 1, 2, 3, and 4 days post-injury. We found that the expression levels of HIF-1α and AQP4 were significantly upregulated in the ethanol-pretreated groups, whereas the VEGF expression level was not. In addition, there was a positive correlation between HIF-1α and AQP4. The results of this study indicate that cytotoxic brain edema may play an important role in the early stage of FPI in ethanol-pre-treated animals and that HIF-1α and AQP4 might be involved. [ABSTRACT FROM AUTHOR]

Most Plasmodium falciparum-infected children with cerebral malaria (CM) die from respiratory arrest, but the underlying pathology is unclear. Here we present a model in which the ultimate cause of death from CM is severe intracranial hypertension. Dynamic imaging of mice infected with P. berghei ANKA, an accepted model for experimental CM, revealed that leukocyte adhesion impairs the venous blood flow by reducing the functional lumen of postcapillary venules (PCV). The resulting increase in intracranial pressure (ICP) exacerbates cerebral edema formation, a hallmark of both murine and pediatric CM. We propose that two entirely different pathogenetic mechanisms--cytoadherence of P. falciparum-infected erythrocytes in pediatric CM and leukocyte arrest in murine CM--result in the same pathological outcome: a severe increase in ICP leading to brainstem herniation and death from respiratory arrest. The intracranial hypertension (IH) model unifies previous hypotheses, applies to human and experimental CM alike, eliminates the need to explain any selective recognition mechanism Plasmodium might use to target multiple sensitive sites in the brain, and explains how an intravascular parasite can cause so much neuronal dysfunction. [ABSTRACT FROM AUTHOR]