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At least 1,153 records · Page 64Linked to original sources
PubMed2003

Brain tissue oxygen response in severe traumatic brain injury.

OBJECTIVE: To investigate clinical relevance and prognostic value of brain tissue oxygen response (TOR: response of brain tissue pO(2) to changes in arterial pO(2)) in traumatic brain injury (TBI). PATIENTS AND METHODS: In a prospective cohort study TOR was investigated in 41 patients with severe TBI (Glasgow Coma Score < or =8) in whom continuous monitoring of brain tissue oxygen pressure (PbrO(2)) was performed.TOR was investigated each day over a five day period for 15 minutes by increasing FiO(2) on the ventilator setting. FiO(2) was increased directly from baseline to 1.0 for a period of 15 minutes under stable conditions (145 tests). In 34 patients the effect of decreasing PaCO(2) was evaluated on TOR by performing the same test after increasing inspiratory minute volume on the ventilator setting to 20% above baseline. Arterial blood gas analysis was performed before and after changing ventilator settings. Multimodality monitoring, including PbrO(2) was performed in all patients. Outcome at six months was evaluated according to the Glasgow Outcome Scale. For statistical analysis the Mann-whitney U-test was used for ordinally distributed variables, and the Chi-square test for categorical variables. Predictive value of TOR was analyzed in a multivariable model. RESULTS: 145 tests were available for analysis. Baseline PbrO(2) varied from 4.0 to 50 mmHg at PaO(2) values of 73-237 mmHg. At FiO(2) settings of 1.0, PbrO(2) varied from 9.1-200 mmHg and PaO(2) from 196-499 mmHg. Three distinct patterns of response were noted: response type A is characterized by a sharp increase in PbrO(2), reaching a plateau within several minutes; type B by the absence of a plateau, and type C by a short plateau phase followed by a subsequent further increase in PbrO(2). Patterns characterized by a stable plateau (type A), considered indicative of intact regulatory mechanisms, were seen more frequently from 48 hours after injury on. If present within the first 24 hours after injury such a response was related to more favorable outcome (p = 0.06). Mean TOR of all tests was 0.73 +/- 0.59 with an median TOR of 0.58. Patients with an unfavourable outcome had a higher TOR (1.03 +/- 0.60) during the first 24 hours, compared to patients with a favorable outcome (0.61 +/- 0.51; p = 0.02). Multiple logistic regression analysis supported the independent predictive value of tissue oxygen response for unfavorable outcome (odds ratio 4.8). During increased hyperventilation, mean TOR decreased substantially from 0.75 +/- 0.54 to 0.65 +/- 0.45 (p = 0.06; Wilcoxon test). Within the first 24 hours after injury a decrease in TOR following hyperventilation was significantly related to poorer outcome (p = 0.01). CONCLUSIONS: Evaluation of TOR affords insight in (disturbances in) oxygen regulation after traumatic brain injury, is of prognostic value and may aid in identifying patients at (increased) risk for ischemia.

Adolescent↗
PubMed1983

A modified method for measurement of radiotracer permeation across the rat blood--brain barrier: the problem of correcting brain uptake for intravascular tracer.

A modified technique to assess integrity of the rat blood--brain barrier is described in which a poorly permeating radiotracer is injected intravenously and its net permeation across the cerebral vasculature in 30 min is related to its time-averaged level in the circulation. At the termination of experiments, direct carotid arterial perfusion clears blood from brain in 30 s and permits measurement of the tracer level in brain parenchyma without correction for intravascular tracer. Constant-rate withdrawal of a single arterial blood sample throughout the period of tracer circulation replaces the need for repeated blood sampling and graph plotting to determine the time-integrated plasma tracer level. During the first 2-3 min following intravenous injection of [3H]mannitol or [14C]sucrose, permeation across the barrier occurred at a rate substantially greater than that measured for a 30 min circulation time. The relatively rapid uptake of these tracers into brain during the first few minutes after injection would explain in part why estimates of regional blood volume, calculated from ratios of brain vs blood tracer concentration after short circulation times, were much higher than values determined using [51Cr]erythrocytes.

Animals↗
PubMedDate not supplied

Brain-stem auditory evoked potentials and brain death.

BAEP records were obtained from 30 brain-dead patients. Three BAEP patterns were observed: (1) no identifiable waves (73.34%), (2) an isolated bilateral wave I (16.66%), and (3) an isolated unilateral wave I (10%). When wave I was present, it was always significantly delayed. Significant augmentation of wave I amplitude was present bilaterally in one case and unilaterally in another. On the other hand, in serial records from 3 cases wave I latency tended to increase progressively until this component disappeared. During the same period, wave I amplitude fluctuations were observed. A significant negative correlation was found for wave I latency with heart rate and body temperature in 1 case. Two facts might explain the progressive delay and disappearance of wave I in brain-dead patients: a progressive hypoxic-ischaemic dysfunction of the cochlea and the eighth nerve plus hypothermia, often present in brain-dead patients. Then the incidence of wave I preservation reported by different authors in single BAEP records from brain-dead patients might depend on the moment at which the evoked potential study was done in relation to the onset of the clinical state. It is suggested that, although BAEPs provide an objective electrophysiological assessment of brain-stem function, essential for BD diagnosis, this technique could be of no value for this purpose when used in isolation.

Adolescent↗
PubMed1991

Regional distribution study of brain perfusion and metabolic agents in normal and tumour bearing rat brains using autoradiographic technique.

Regional distribution of brain perfusion imaging agents, [131I]N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5-iodobenzyl]1,3 propanediamine (HIPDM) and [131I]-N-isopropyl-p-iodoamphetamine (IMP), was compared with the distribution of patterns of [14C]L-methionine and [14C]D-glucose in normal and tumour bearing rat brains using autoradiographic technique. There was higher concentration of the radiopharmaceutical in grey than white matter in normal rat brain. Autoradiographs of brain tumour sections showed very low uptake of [131I]HIPDM and [131I]IMP as compared to normal brain tissue. There was moderate concentration of [14C]D-glucose and avid uptake of [14C]L-methionine in tumours. Autoradiographic study is useful for evaluating distribution patterns of radiopharmaceuticals.

Amphetamines↗
PubMed2026

Understanding specificity in immune-brain pathways: A systematic review of differential associations between individual cytokines and brain structure and function measured through magnetic resonance imaging in humans.

Research shows that cytokines are associated with psychiatric disorders, including major depression, and multiple aspects of brain structure and function. Accumulating data suggest that different cytokines may have unique profiles of biological activity, particularly in their neuromodulatory roles, but it is currently unclear whether they have unique associations with specific neural circuits in humans. In this paper, we systematically review magnetic resonance imaging studies conducted with depressed or healthy control human participants under age 65 that examine associations between peripheral cytokines and brain structure and function, with the goal of evaluating evidence for the specificity of these cytokine-brain associations. We find that across multiple measures of brain structure and function, the majority of studies reviewed reported unique associations between individual cytokines and brain outcomes. A synthesis of findings across studies also suggests a preliminary hypothesis of specific associations of interleukin-6 levels in circulation with the default mode network and tumor necrosis factor-alpha with the salience network, which could be tested in future research. We conclude the review with future directions for research that can strengthen understanding of these associations.

Humans↗
PubMed2004

Continuous measurements of cerebral tissue oxygen pressure during hyperbaric oxygenation--HBO effects on brain edema and necrosis after severe brain trauma in rabbits.

INTRODUCTION: Severe brain injury is one of the most frequent causes of severe disability in the young. In acute management of brain trauma, new approaches based on experimental animal investigations should be sought. METHODS: Twenty male, juvenile Chinchilla-Bastard rabbits received standardized cold-injury-induced-brain-trauma (CIBT). A metal probe (temperature -196 degrees C) was applied epidurally over 10 s. The hyperbaric oxygenation (HBO) group (n=10) underwent 90-min HBO sessions with 100% oxygen at 2.5 atmospheres absolute (1 h, 24+/-2 h, 48+/-2 h after CIBT). Cerebral tissue pO2-measurements were performed 60 min after CIBT, during the three HBO sessions and on day 4. The control group (n=10) underwent no treatment. Animals were sacrificed on day 4, and brains were analyzed histologically. RESULTS: In the HBO group, pO2 measurements showed a significant increase in pO2 between day 1 and day 4, whereas no significant changes were observed in the control group. During the first HBO session, mean pO2 was 169 mm Hg, during the second 305 mm Hg and during the third 420 mm Hg. The mean area of necrosis was 16.2 mm2 in the HBO group, in the control group 19.9 mm2. The areas of brain edema were significantly smaller in the HBO group. Mortality in the HBO group was 0%, in the control group 20%. CONCLUSION: HBO appears to be beneficial as an adjunct treatment of severe head trauma. To find optimal treatment protocols, further clinical studies must be developed.

Animals↗
PubMed2005

A case of generalized hypoxic brain damage following traumatic brain damage.

In forensic autopsy cases, transient brain hypoxia can be induced by cardiac arrest, hypovolemic shock, and other conditions with severe circulatory failure. Although cortical laminar necrosis in watershed areas between territories of the major cerebral arteries is occasionally seen, cases with global hypoxic damage to the brain is rare, because patients with irreversible severe brain damage rarely survive for more than a few days. In this report we describe autopsy results for an injury victim who survived unconscious for approximately 4 weeks after admission. Macroscopic thinning of the gray matter and uniformly cheesecake-like cloudy changes in white matter were observed. Microscopically, cortical laminar necrosis was observed in all lobes of the cerebrum, and massive gliosis was diffused throughout the white matter. We speculate that traumatic brain damage, continuous hypoxemia, and many other factors induced these characteristic pathological changes during the long time interval from brain damage to death.

Brain↗
PubMed1999

Regional changes in the expression of neurotrophic factors and their receptors following acute traumatic brain injury in the adult rat brain.

We have analyzed the effect of severe traumatic brain injury (TBI) on the levels of mRNA expression of neurotrophic factors (NTFs): brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF) and their respective receptors: trkB, trkA and CNTFRalpha. The expression was examined in the region of the lesion as well as a region remote from the lesion at 12, 24, and 36 h following the injury. Our data suggest that after the brain injury, the expression of NGF and BDNF mRNAs were early, transiently and significantly upregulated while that of CNTF was a slow and less amplified response in both areas of the brain. We also found that trkA mRNA expression was only upregulated significantly in the remote area; trkB mRNA showed no significant change in either area except an upregulation at 12 h in the remote area. CNTFRalpha was downregulated significantly by 24-36 h in the lesion area and by 24 h in the remote area. These changes suggest that TBI regulates the expression of NTFs and their receptors. These alterations in expression may be involved in modulating the neuronal response after brain injury.

Age Factors↗
PubMed2000

Boron neutron capture therapy of brain tumors: enhanced survival and cure following blood-brain barrier disruption and intracarotid injection of sodium borocaptate and boronophenylalanine.

PURPOSE: Boronophenylalanine (BPA) and sodium borocaptate (Na(2)B(12)H(11)SH or BSH) have been used clinically for boron neutron capture therapy (BNCT) of high-grade gliomas. These drugs appear to concentrate in tumors by different mechanisms and may target different subpopulations of glioma cells. The purpose of the present study was to determine if the efficacy of BNCT could be further improved in F98-glioma-bearing rats by administering both boron compounds together and by improving their delivery by means of intracarotid (i.c.) injection with or without blood-brain barrier disruption (BBB-D). METHODS AND MATERIALS: For biodistribution studies, 10(5) F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Eleven to 13 days later animals were injected intravenously (i.v.) with BPA at doses of either 250 or 500 mg/kg body weight (b.w.) in combination with BSH at doses of either 30 or 60 mg/kg b.w. or i.c. with or without BBB-D, which was accomplished by i.c. infusion of a hyperosmotic (25%) solution of mannitol. For BNCT studies, 10(3) F98 glioma cells were implanted intracerebrally, and 14 days later animals were transported to the Brookhaven National Laboratory (BNL). They received BPA (250 mg/kg b.w.) in combination with BSH (30 mg/kg b.w. ) by i.v. or i.c. injection with or without BBB-D, and 2.5 hours later they were irradiated with a collimated beam of thermal neutrons at the BNL Medical Research Reactor. RESULTS: The mean tumor boron concentration +/- standard deviation (SD) at 2.5 hours after i. c. injection of BPA (250 mg/kg b.w.) and BSH (30 mg/kg b.w.) was 56. 3 +/- 37.8 microgram/g with BBB-D compared to 20.8 +/- 3.9 microgram/g without BBB-D and 11.2 +/- 1.8 microgram/g after i.v. injection. Doubling the dose of BPA and BSH produced a twofold increase in tumor boron concentrations, but also concomitant increases in normal brain and blood levels, which could have adverse effects. For this reason, the lower boron dose was selected for BNCT studies. The median survival time was 25 days for untreated control rats, 29 days for irradiated controls, 42 days for rats that received BPA and BSH i.v., 53 days following i.c. injection, and 72 days following i.c. injection + BBB-D with subsets of long-term survivors and/or cured animals in the latter two groups. No histopathologic evidence of residual tumor was seen in the brains of cured animals. CONCLUSIONS: The combination of BPA and BSH, administered i.c. with BBB-D, yielded a 25% cure rate for the heretofore incurable F98 rat glioma with minimal late radiation-induced brain damage. These results demonstrate that using a combination of boron agents and optimizing their delivery can dramatically improve the efficacy of BNCT in glioma-bearing rats.

Animals↗
PubMed1985

The effect of perinatal anoxia on amino acid metabolism in the developing brain. Part I: The effect of experimental anoxia on the free amino acid patterns in the brain of neonatal rats.

The effect of perinatal anoxia on the subsequent amino acid pattern in the brain during a period of 2 wks after birth was investigated using neonatal rats. Sixty-nine neonatal albino rats of the Wistar strain were divided into 3 groups: the 1st control group (n = 36), the 2nd anoxic group (n = 30) and the 3rd anoxic-ischemic group (n = 3). In the 1st and 2nd groups, 6 rats out of each group were sacrificed on the each of the following days respectively, the 1st, 3rd, 5th, 7th, 10th and 15th days of life for amino acid assays of brain. In the 3rd group, 3 rats were sacrificed 2 days after ligation of the carotid artery on one side, and free amino acid levels in both cerebral hemispheres were separately measured. In the controls, the levels of GABA, Asp and Glu in the brain increased, those of Tau and Gly decreased and those of PE, Thr, Ser, Gln, Ala and Leu did not change during the experimental period. The total free amino acid level in the brain of the controls remained almost completely unchanged during this period. After anoxic exposure the levels of GABA, Tau, PE, Asp, Thr, Glu, Gln and Ala, and the total free amino acid level in the brain decreased until the 7th day of life and thereafter rapidly increased. The Gly level continuously decreased and the Ser and Leu levels did not change during the experiment. The GABA and Gly levels after anoxia decreased and were still low on the 15th day of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed2003

[Blood-brain barrier pathophysiology and ischaemic brain oedema].

Cerebral oedema is a potentially lethal complication of brain infarction. Ischemia, by altering membrane ionic pump function, induces cell swelling and cytotoxic oedema. It also initiates early oxidative and inflammatory cascades leading to blood-brain barrier disruption, vasogenic oedema and haemorrhagic transformation. The mechanisms of blood-brain barrier disruption involve endothelial cell activation and endothelial basal membrane degradation by matrix metalloproteinases. Reperfusion by tissue plasminogen activators is the only treatment improving stroke prognosis. This treatment also increases vasogenic oedema and the risk of symptomatic haemorrhagic transformation, reducing the benefit of reperfusion. Experimental studies suggest that the inhibition of blood-brain barrier proteolysis reduces vasogenic oedema and the risk of haemorrhage. This recent progress in the understanding of blood-brain barrier disruption during ischaemia brings forward new therapeutic strategies using agents capable of interfering with the ischaemic cascade in order to increase the therapeutic window between the onset of ischaemia and thrombolytic reperfusion.

Blood-Brain Barrier↗
PubMed2000

Boron neutron capture therapy of brain tumors: functional and neuropathologic effects of blood-brain barrier disruption and intracarotid injection of sodium borocaptate and boronophenylalanine.

Sodium borocaptate (BSH) and boronophenylalanine (BPA) are two drugs that have been used clinically for boron neutron capture therapy (BNCT) of brain tumors. We previously have reported that hyperosmotic mannitol-induced disruption of the blood-brain barrier (BBB-D), followed by intracarotid (i.c.) administration of BPA or BSH, either individually or in combination, significantly enhanced tumor boron delivery and the efficacy of BNCT in F98 glioma bearing rats. The purpose of the present study was to determine the short-term neuropathologic consequences of this treatment and the long-term effects on motor and cognitive function, as well as the neuropathologic sequelae 1 year following neutron capture irradiation. BBB-D was carried out in non-tumor bearing Fischer rats by infusing a 25% solution of mannitol i.c. followed by i.c. injection of BPA or BSH, either individually or in combination, immediately thereafter. Animals were euthanized 2 days after compound administration, and their brains were processed for neuropathologic examination, which revealed sporadic, mild, focal neuronal degeneration, hemorrhage, and necrosis. To assess the long-term effects of such treatment followed by neutron capture irradiation, non-tumor bearing rats were subjected to BBB-D after which they were injected i.c. with BPA (25 mg B/kg body weight (b.w)) or BSH (30 mg B/kg b.w.) either individually or in combination (BPA 12.5 mg and BSH 14 mg B/kg b.w.). Two and a half hours later they were irradiated at the Medical Research Reactor, Brookhaven National Laboratory, Upton, NY, with the same physical radiation doses (5.79, 8.10 or 10.06 Gy), delivered to the brain, as those that previously had been used for our therapy experiments. The animals tolerated this procedure well, after which they were returned to Columbus, Ohio where their clinical status was monitored weekly. After 1 year, motor function was assessed using a sensitive and reliable locomotor rating scale for open field testing in rats and cognitive function was evaluated by their performance in the Morris water maze, the results of which were similar to those obtained with age matched controls. After functional evaluation, the rats were euthanized, their brains were removed, and then processed for neuropathologic examination. Subtle histopathologic changes were seen in the choroid plexuses of irradiated animals that had received BPA, BSH or saline. Radiation related ocular changes consisting of keratitis, blepharitis, conjunctivitis and cataract formation were seen with similar frequency in most rats in each treatment group. Based on these observations, and the previously reported significant therapeutic gain associated with BBB-D and i.c. injection of BSH and BPA, the present observations establish its safety in rats and suggest that further studies in large animals and humans are warranted.

Animals↗
PubMed1991

Increased levels of type VIII collagen in human brain tumours compared to normal brain tissue and non-neoplastic cerebral disorders.

The expression of type VIII collagen was examined in the normal and diseased human brain. Focal immunoreactivity was seen in histologically abnormal vessels of all four angiomas and 40 of 52 brain tumours (gliomas, meningiomas and schwannomas). An extended staining pattern, as well as a punctate distribution, was frequently observed in affected vessels. Staining was not apparent in nine normal brains and in 15 pathologic brains showing various cerebrovascular abnormalities, including Alzheimer's, Leigh's and Wernicke's diseases. Immunoblotting of glioblastomas revealed two bands at 56 kD and 67 kD which were also present at low levels in normal frontal cortex. The extracellular distribution of type VIII collagen was different from that of the other collagen types which have been described in brain and resembles patterns of expression described for certain tissues during mammalian embryogenesis (Kapoor et al., 1988). Our results provide additional evidence for the participation of type VIII collagen in some types of angiogenesis.

Adult↗
PubMed2003

In vivo delivery of glial cell-derived neurotrophic factor across the blood-brain barrier by gene transfer into brain capillary endothelial cells.

The gene encoding mouse glial cell-derived neurotrophic factor (mGDNF gene) was transfected into brain capillary endothelial cells (BCECs) with the aim of delivering the gene product extensively into the brain parenchyma by making use of the secretory function of BCECs. First, we transfected mGDNF gene into cultured BCECs (MBEC4; mouse brain capillary endothelial cells) in vitro. The amount of mGDNF protein secreted from the transfected cells into the medium was 1500 to 3200 pg/mg of cell protein per day, being about sevenfold higher than that accumulated intracellularly. Furthermore, the basolateral-directed secretion of mGDNF protein from the transfected MBEC4 cells was fivefold higher than the apical-directed secretion. Next, the hemagglutination virus of Japan (HVJ)-liposomes encapsulating mGDNF gene were administered to rats in vivo via the internal carotid artery. The transfected rats showed a marked increase in the brain level of GDNF as assessed by means of enzyme-linked immunosorbent assay (ELISA) and Western blotting on day 3 after the administration, and the level remained significantly elevated for at least 12 days. Furthermore, immunohistochemical staining revealed an increase in GDNF immunoreactivity throughout the transfected forebrain. These results indicate that the gene was successfully transferred in vivo from HVJ-liposomes into BCECs, where it was expressed, and the gene product was secreted into the brain. Then, using this delivery method, we evaluated the protective effect for dopamine neuron against a retrograde 6-hydroxydopamine (6-OHDA) lesion, as assessed by behavioral and neurochemical indices.

Animals↗
PubMed2000

Enoxaparin reduces brain edema, cerebral lesions, and improves motor and cognitive impairments induced by a traumatic brain injury in rats.

Traumatic brain injury (TBI) is often accompanied by secondary ischemia due, in part, to edema-induced blood vessel compression. Enoxaparin, a low-molecular weight heparin, which is efficacious in models of myocardial and brain ischemia was studied in lateral fluid percussion-induced TBI in rats. Enoxaparin was administered 2 h post-TBI at 0.5 mg/kg i.v. followed by 4 x 0.5, 4 x 1, or 4 x 2 mg/kg s.c. over 30 h. Brain edema was measured in the hippocampus, temporal cortex and parietal cortex. Edema was reduced by enoxaparin (0.5 + 4 x 0.5 mg/kg) in the hippocampus (-53%, p = 0.07) and the parietal cortex (-39%, ns). At 0.5 + 4 x 1 mg/kg edema was reduced in the hippocampus (-63%, p < 0.05) and the parietal cortex (-47%, p = 0.06). At 0.5 + 4 x 2 mg/kg, the reduction was more important in the hippocampus (-69%, p < 0.01) and in the parietal cortex (-50%, p < 0.05). No reduction was seen in the temporal cortex. The lesion size was reduced by enoxaparin at 0.5 + 4 x 1 mg/kg (-50%, p < 0.05), and at 0.5 + 4 x 2 mg/kg (-35%, ns). The neurological deficit evaluated with a 9-point scale was also improved with enoxaparin at 0.5 + 4 x 1 mg/kg 1 week post-TBI (p < 0.05). The cognitive impairment evaluated with a Lashley maze task was improved with enoxaparin (0.5 + 4 x 1 mg/kg) from 48 h (p < 0.05) to 2 weeks post-TBI (p < 0.01). Our results demonstrate for the first time that enoxaparin significantly reduces the brain contusion and edema, and improves the functional outcomes induced by a TBI. Therefore, enoxaparin could be a candidate drug to treat acute brain-injured patients.

Animals↗
PubMed1998

Improving drug delivery to intracerebral tumor and surrounding brain in a rodent model: a comparison of osmotic versus bradykinin modification of the blood-brain and/or blood-tumor barriers.

OBJECTIVE: To compare transient blood-brain barrier disruption (BBBD) by hypertonic mannitol with pharmacological modification of the blood-tumor barrier by the vasoactive peptide bradykinin for delivery of small and large agents to nude rat intracerebral xenografts. METHODS: Female nude rats (n = 104) with 6-day intracerebral human small cell lung carcinoma tumors were treated using BBBD (n = 24), intracarotid bradykinin (n = 38), or saline (controls, n = 32) administered intra-arterially. During or immediately after infusion, the rats were given radiolabeled agent (methotrexate or dextran 70; Dupont NEN, Boston, MA). The rats were killed 10 minutes later, and samples of tumor and brain regions were obtained for scintillation counting. Twenty-two additional rats were examined using magnetic resonance imaging after administering one of two contrast agents (gadoteridol or iron oxide nanoparticles) or saline (controls) in conjunction with BBBD or bradykinin. RESULTS: After BBBD, the delivery of both small (methotrexate) and large (dextran 70) radiolabeled tracers was increased 2- to 6-fold in the tumor and 3- to 20-fold in surrounding brain, as compared with saline controls. After bradykinin treatment, there was minimal change in delivery of methotrexate or dextran 70 to tumor and brain around tumor, with the greatest increase less than 60% over controls. Magnetic resonance imaging demonstrated increased delivery of both small and large contrast agents to the treated hemisphere after BBBD. In comparison, no increased tumor enhancement could be detected after bradykinin treatment. CONCLUSION: BBBD resulted in global delivery of a variety of agents in a wide range of sizes. In this human brain tumor xenograft model, bradykinin was not effective at increasing delivery to the tumor of any agent tested.

Animals↗
PubMed2004

The management of brain edema in brain tumors.

This review focuses on pathophysiology, clinical signs, and imaging of brain edema associated with intracranial tumors and its treatment. Brain edema in brain tumors is the result of leakage of plasma into the parenchyma through dysfunctional cerebral capillaries. The latter type of edema (ie, vasogenic edema) and the role of other types in brain tumors is discussed. Vascular endothelial growth factor-induced dysfunction of tight junction proteins probably plays an important role in the formation of edema. Corticosteroids are the mainstay of treatment of brain edema. When possible, corticosteroids should be used in a low dose (eg, 4 mg dexamethasone daily) to avoid serious side effects such as myopathy or diabetes. Higher doses of dexamethasone (16 mg/day or more), sometimes together with osmotherapy (mannitol, glycerol) or surgery, may be used in emergency situations. On tapering, one should be aware of the possible development of corticosteroid dependency or withdrawal effects.Novel therapies include vascular endothelial growth factor receptor inhibitors and corticotropin releasing factor, which should undergo further clinical testing before they can be recommended in practice.

Blood-Brain Barrier↗
PubMed1985

Alterations of the eicosanoid synthetic capacity of rat brain microvessels following ischemia: relevance to ischemic brain edema.

To know the mechanism underlying ischemic brain edema, a time-course analysis of the eicosanoid synthetic capacity of brain microvessels was carried out using unilateral, middle cerebral artery (MCA)-occluded rats. Concomitant with the development of brain edema the synthetic capacity of all products, including cyclooxygenase and lipoxygenase products, increased significantly. Next the effects of 15-hydroperoxyarachidonic acid (15-HPAA) on the synthetic capacity of microvessels were examined. The drug caused a generalized increase of each product, the profile of which was similar to that obtained with ischemic hemispheres, although the ratios of each product differed somewhat among them. The enhanced synthesis of eicosanoids by 15-HPAA was markedly suppressed by radical scavengers such as alpha-tocopherol, hydroquinone, and 1,2-bis(nicotineamide)-propane. Furthermore, the evolution of brain edema was virtually suppressed by the systemic administration of 1,2-bis(nicotineamide)-propane. The above result suggests that the enzyme activity of the arachidonic acid (AA) cascade of microvessels is stimulated by its own products. Such a mechanism will form a vicious cycle that accelerates the accumulation of free radicals within microvessels and thus may play a role in the progressing disruption of the blood-brain barrier (BBB) following ischemia.

Animals↗