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PubMed1995

Alternative RNA splicing of the hyaluronic acid receptor CD44 in the normal human brain and in brain tumors.

The cell-surface receptor for hyaluronic acid, CD44, is expressed by both normal and malignant cells. Numerous CD44 isoforms have recently been identified that are derived by alternative ribonucleic acid splicing. The expression of some CD44 isoforms has been shown to be involved in tumor progression and metastatic spread in a rat carcinoma model and in human carcinomas. In the present study, CD44 isoform expression was evaluated by reverse transcriptase-polymerase chain reaction (PCR) analysis in frozen sections derived from three samples of normal brain tissue and from 40 brain tumors, including samples of glioblastoma multiforme, anaplastic astrocytoma, low-grade astrocytoma, cerebral primitive neuroectodermal tumor, medulloblastoma, metastatic colon carcinoma, and metastatic melanoma. Normal brain tissue adjacent to the tumors was also examined in 14 of 18 glioblastomas. In all normal brain and tumor samples, with the exception of metastases from colon carcinoma, PCR analysis demonstrated one prominent product that corresponded to the CD44H hematopoietic form of CD44. Metastases from colon carcinoma demonstrated two prominent PCR amplification products corresponding to CD44H and CD44R1. These results suggest that CD44H is the predominant isoform of this protein in normal human brain tissue and in human neuroectodermal tumors of varying degrees of malignancy. The ability of CD44H to mediate tumor cell motility and invasiveness (in contrast to CD44R1) suggests that the CD44 alternative splicing pattern of neuroectoderm-derived tumors may enhance their local biological aggressiveness and intracerebral spread. The lack of expression of larger molecular weight CD44 variants by primary brain tumors may also partially explain why these tumors rarely metastasize to distant sites.

Alternative Splicing↗

PubMed2003

Effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury.

OBJECTIVE: To observe the effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury (TBI). METHODS: An acute experimental closed TBI model in rats was induced by a fluid-percussion brain injury model. At five and sixty minutes after TBI, the animals were intraperitoneally injected by ganglioside GM1 (30 mg/kg) or the same volume of saline. At the 6th hour after TBI, effects of ganglioside GM1 or saline on changes of mean arterial pressure (MAP), contents of water, lactic acid (LA) and lipid peroxidation (LPO) in the injured cerebral tissues were observed. RESULTS: After TBI, MAP decreased and contents of water, LA and LPO increased in brain injury group; however, MAP was back to normal levels and contents of water, LA and LPO decreased in ganglioside GM1 treated group, compared with those in brain injury group (P < 0.05). No significant difference between the saline treated group and the brain injury group (P > 0.05) was observed. CONCLUSIONS: Ganglioside GM1 does have obvious neuroprotective effect on early TBI.

Animals↗

PubMed2004

Efficacy assessment of cerebral arterial bypass surgery using statistical parametric mapping and probabilistic brain atlas on basal/acetazolamide brain perfusion SPECT.

UNLABELLED: The efficacy of cerebral arterial bypass surgery was assessed on brain perfusion SPECT using statistical parametric mapping (SPM) and a probabilistic brain atlas. METHODS: Fifteen patients with ischemia in the internal carotid artery (ICA) territory and 21 age-matched healthy volunteers were enrolled. (99m)Tc-HMPAO basal/acetazolamide brain perfusion SPECT was performed 2 wk before and after bypass surgery and also on a healthy control group. Using SPM analysis, group comparisons were made between pre- and postoperative SPECT for each basal/acetazolamide image, and improvements of perfusion and perfusion reserve were assessed. The number of significant voxels on the SPM analysis was defined as the extent of ischemia. With the use of the probabilistic brain atlas, the counts for the cerebral lobes and the ICA territory were automatically calculated for each image and compared. RESULTS: The group comparisons by SPM between patients and healthy volunteers showed a significant improvement in general perfusion status in the ICA territory. The improvement in perfusion reserve was more extensive than the improvement in perfusion. The extent of ischemia was also significantly decreased after surgery (1,693 +/- 2,604 to 371 +/- 523 voxels in basal images, P = 0.060; 11,879 +/- 6,449 to 5,997 +/- 3,864 voxels in acetazolamide images, P = 0.005). In the analysis using the probabilistic brain atlas, the preoperatively decreased perfusion was normalized after surgery, but a residual decrease in the perfusion reserve was also observed in the ICA territory. The counts in the volume of interest of the ICA territory were significantly improved (38.5 +/- 4.1 to 41.5 +/- 2.7 in basal images, P = 0.024; 34.2 +/- 4.4 to 38.8 +/- 2.9 in acetazolamide images, P = 0.003). One patient showing a decrease in perfusion had a perioperative cerebral infarct. CONCLUSION: Using SPM and a probabilistic brain atlas, the perfusion, the perfusion reserve, and changes in both after cerebral arterial bypass surgery were effectively assessed and correlated well with physiologic reasoning.

Acetazolamide↗

PubMed2006

[Expression of c-myc protein on rats' brains after brain concussion].

OBJECTIVE: To study the changes of expression of c-myc protein on rats' brains after brain concussion. METHODS: sixty rats were randomly divided into brain concussion groups and control group. The expression of c-myc protein was microscopically observed by immunohistochemical method. RESULTS: No expression of c-myc protein in control group were observed. However, positive expression of c-myc protein in some neurons was seen at 20 min after brain concussion, and reach to the peak at 8h after brain concussion and then decreased gradually. CONCLUSION: These findings suggest that the detection of c-myc protein could be an index of diagnosis of brain concussion.

Animals↗

PubMed1990

Blood-to-brain sodium transport in ischemic brain edema.

Brain edema is a frequent complication of cerebral ischemia; however, its mechanism of formation is not well understood. Sodium is known to accumulate in brain during the early stages of partial ischemia. Therefore, the present studies were undertaken to determine the relation among BBB sodium transport, integrity of the BBB, and development of brain edema during the first 24 hr after the onset of cerebral ischemia. Partial cerebral ischemia was produced in gerbils by ligation of the left common carotid artery under ether anesthesia. After recovery from the anesthetic, animals were scored for the presence of symptoms, and those with scores greater than 10 of 25 (n = 87) were chosen for this study. Measurements of tissue water, sodium, and potassium contents, and brain uptake of 22Na and 3H-mannitol were made in each group at 1.5, 3, 6, 12, and 24 hr after carotid ligation. Accumulation of sodium and water in the ischemic compared with the nonischemic cerebral cortex was progressive. This edema formation was not of the vasogenic type because the permeability of the BBB to mannitol was unchanged. Blood-to-brain sodium transport was reduced by 30% to 40% at all time points in the ischemic cortex. Nevertheless, the remaining sodium transport activity appeared to play a role in the development of brain edema because Na accumulated in the tissue at a rate that was approximately the same as the rate of 22Na uptake from blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Brain edema and the blood brain barrier in galactosamine-induced fulminant hepatic failure rats. An animal model for evaluation of liver support systems.

Rats with galactosamine-induced fulminant hepatic failure (FHF) have been a popular animal model for the evaluation of liver support systems. Because development of brain edema is a major and frequent complication during FHF, it was studied for this report. The degree of hepatocyte necrosis closely paralleled the severity of coma. Abnormalities in the orientation of hepatocellular organelles were evident as early as grade I hepatic coma, 24 hr after galactosamine-induced liver damage. Galactosamine caused a characteristic pattern of hepatocyte necrosis such that the endoplasmic reticulum completely surrounded the nucleus to cause karyolysis and subsequent cell death. Quantitative measurements of brain water content revealed evidence of brain edema with increasing severity of coma. Brain edema resulted in a greater than 4% swelling of the brain during this period. Light microscopy showed increasing cerebral and cerebellar edema during progressive stages of FHF. Electron microscopy studies revealed evidence of progressive cerebral edema, particularly in the perivascular region of cerebral capillaries. Marked swelling of perivascular astrocytes was evident as early as 24 hr after galactosamine-induced FHF when the animals were in Grade I hepatic coma. Abnormal swelling and distortion of astroglia, including its subcellular organelles, and the presence of cytoplasmic vacuoles, was clearly evident during the deeper stages of hepatic coma (Grades II-IV). Trypan blue dye infusion studies revealed evidence of extensive blood-brain barrier (BBB) breakdown beginning in Grade III coma.

Animals↗

PubMed2025

Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma.

Post-traumatic stress (PTS) encompasses a range of psychological responses following trauma, which may lead to more severe outcomes such as post-traumatic stress disorder (PTSD). Identifying early neuroimaging biomarkers that link brain function to PTS outcomes is critical for understanding PTSD risk. This longitudinal study examines the association between brain dynamic functional network connectivity (dFNC) and current/future PTS symptom severity, and the impact of sex on this relationship. By analyzing 275 participants' dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=-0.197, p corrected = 0.0079) and future (r=-0.176, p corrected = 0.0176) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.205, p corrected = 0.0079). We additionally observed that the association between the network dynamics of the inter-network and intra-network brain state with symptom severity is more pronounced in female group. Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger effect in female group, underscoring the importance of sex differences.

Journal Article↗

PubMed2001

Matrix metalloproteinase (MMP) system in brain: identification and characterization of brain-specific MMP highly expressed in cerebellum.

The matrix metalloproteinase (MMP) family, comprising more than 20 isoforms, modulates the extracellular milieu by degrading extracellular matrix (ECM) proteins. Because MMP is one of the few groups of proteinases capable of hydrolysing insoluble fibrillar proteins, they are likely to play crucial roles in regulating both normal and pathophysiological processes in the brain. However, little is yet known about their possible neuronal functions due presumably to their unusual redundancy and to the absence of a complete catalogue of isoforms. As an initial step in understanding the MMP system in the brain, we analysed an expression spectrum of MMP in rat brain using RT-PCR and discovered a novel brain-specific MMP, MT5-MMP. MT5-MMP was the predominant species among the nongelatinase-type isoforms in brain. MT5-MMP, present in all brain tissues examined, was most strongly expressed in cerebellum and was localized in the membranous structures of expressing neurons, as assessed biochemically and immunohistochemically. In cerebellum, its expression was regulated developmentally and was closely associated with dendritic tree formation of Purkinje cells, suggesting that MT5-MMP may contribute to neuronal development. Furthermore, its stable postdevelopmental expression and colocalization with senile plaques in Alzheimer brain indicates possible roles in neuronal remodeling naturally occurring in adulthood and in regulating pathophysiological processes associated with advanced age.

Alzheimer Disease↗

PubMed1987

Absorptive-mediated endocytosis of cationized albumin and a beta-endorphin-cationized albumin chimeric peptide by isolated brain capillaries. Model system of blood-brain barrier transport.

Cationized albumin (pI greater than 8), unlike native albumin (pI approximately 4), enters cerebrospinal fluid (CSF) rapidly from blood. This suggests that a specific uptake mechanism for cationized albumin may exist at the brain capillary wall, i.e. the blood-brain barrier. Isolated bovine brain capillaries rapidly bound cationized [3H]albumin and approximately 70% of the bound radioactivity was resistant to mild acid wash, which is assumed to represent internalized peptide. Binding was saturable and a Scatchard plot gave a maximal binding capacity (Ro) = 5.5 +/- 0.7 micrograms/mgp (79 +/- 10 pmol/mgp), and a half-saturation constant (KD) = 55 +/- 8 micrograms/ml (0.8 +/- 0.1 microM). The binding of cationized [3H]albumin (pI = 8.5-9) was inhibited by protamine, protamine sulfate, and polylysine (molecular weight = 70,000) with a Ki of approximately 3 micrograms/ml for all three proteins. The use of cationized albumin in directed delivery of peptides through the blood-brain barrier was examined by coupling [3H]beta-endorphin to unlabeled cationized albumin (pI = 8.5-9) using the bifunctional reagent, N-succinimidyl 3-(2-pyridyldithio)proprionate. The [3H]beta-endorphin-cationized albumin chimeric peptide was rapidly bound and endocytosed by isolated bovine brain capillaries, and this was inhibited by unlabeled cationized albumin but not by unconjugated beta-endorphin or native bovine albumin. Cationized albumin provides a new tool for studying absorptive-mediated endocytosis at the brain capillary and may also provide a vehicle for directed drug delivery through the blood-brain barrier.

Animals↗

PubMed1997

[Postoperative brain infarction in a patient with the previous asymptomatic brain infarction].

We report a case of a postoperative brain infarction, in which an asymptomatic preoperative brain infarction was also revealed postoperatively. A 63-year-old man with bladder carcinoma was scheduled for the cystoplasty. The patient had no prominent preoperative abnormality. Anesthesia was maintained with isoflurane in N2O/oxygen combined with a spinal block and a continuous epidural block. Anesthesia lasted uneventfully for 16.5 hours. However, emergence from anesthesia was delayed. On the first postoperative day, motor aphasia and right hemiparalysis was confirmed. The computed tomography (CT) of the brain demonstrated a low density area in the frontoparietal region. The magnetic resonance imaging (MRI) indicated the corresponding lesion as the CT had demonstrated, and an old brain infarction in the parietal region. This meant that the patient had a history of asymptomatic brain infarction (ABI). Patients with ABI are considered to be a high-risk group for a brain infarction. It is important to evaluate the risk factors of brain infarction preoperatively and to minimize those risks during the operation. Maintenance of the cerebral perfusion pressure is imperative.

Anesthesia, Epidural↗

PubMed1984

Temporal correlates in brain death. EEG and clinical relationships to the respirator brain.

In a prospective study of 32 cases of brain death, gross and microscopic pathological appearances of the CNS were statistically analyzed and correlated with EEG and clinical findings. The diagnosis of a "respirator brain" is best made grossly after fixation, using commonly known gross pathological criteria. The microscopic changes are more unpredictable and variable than the gross findings. Respirator brain changes that can be relied on to confirm the clinical-EEG diagnosis of brain death generally take about 12 hours to become manifest after electrocerebral silence (ECS) and/or cerebral circulatory arrest, and are unaffected by the time interval between termination of respiratory support and refrigeration of the body or by delays in performance of the autopsy. Loss of brain-stem reflexes, evidence of herniation, and deterioration of the EEG to ECS correlate significantly with the development of a respirator brain in the respirator-dependent, comatose patient.

Adolescent↗

PubMed1997

Specific degradation of subendothelial matrix proteoglycans by brain-metastatic melanoma and brain endothelial cell heparanases.

One of the many features of the malignant phenotype, in vitro and in vivo, is elevated heparanase production and activity. Using in vitro model systems, we examined the capacity of murine (B16B15b) and human (70W) brain-metastatic melanoma cells to degrade the subendothelial matrix produced by endothelial cell monolayer cultures. B16B15b and 70W melanoma cells solubilized sulfated matrix proteoglycans at levels significantly higher than their parental lines (B16F1, MeWo). Sulfated matrix proteoglycans were rich in heparan sulfate (HSPGs), with minor amounts of chondroitin and dermatan sulfates. When matrix HSPGs were treated with pronase and alkaline borohydride to cleave the core proteins, the resulting glycosaminoglycan chains (GAGs) had an estimated M(r) of approximately 2.7 x 10(4) Da, with a minor subpopulation possessing an M(r) of approximately 4.5 x 10(4) Da. After their incubation with brain-metastatic melanoma cells, new HS fragments with lower M(r) estimated at approximately 9 x 10(3) Da were detected. This confirms action in these cells of heparanase, which is capable of cleaving GAGs at specific intrachain sites and releasing fragments of a relatively high M(r). The pattern of HSPG degradation by brain-metastatic melanoma cells differed from that of less metastatic parental cells or cells metastatic to organs other than the brain. Moreover, supraadditive levels of heparanase activity were found when brain endothelial cells were coin-cubated with brain-metastatic melanoma cells in equicellular amounts. Cooperative interactions between heparanases from tumor and endothelial sources in the invasion process are suggested and their potential mechanisms discussed.

Animals↗

PubMed1992

Pattern of glucose transporter (Glut 1) expression in embryonic brains is related to maturation of blood-brain barrier tightness.

A constant supply of blood-borne glucose is vital to cerebral metabolism. Although transport of glucose into the nervous tissue, effectively separated from the blood by a functional barrier (the blood-brain barrier, BBB), is one of the essential properties of the cerebral endothelium, little is known about its metabolic regulation and developmental expression in the BBB. In this study we provide evidence by immunocytochemistry that the pattern of the brain endothelial glucose transporter in rat brains (BBB-GT), immunologically homologous with the human hepatoma (G2), human erythrocyte transporter (Glut 1), changes with BBB maturation. While the neuroepithelium at embryonic days 12 and 13 shows a high incidence of immuno-detectable BBB-GT, vascularisation of the cerebral anlage and subsequent development of vascular tightness, as evidenced by intravascularly applied horseradish peroxidase and fluorescinated dextrans, is accompanied by a significant reduction of BBB-GT expression in neuroepithelial cells and confinement of BBB-GT expression to the cerebral endothelium. Immunoblots and Northern blots of embryonic brain homogenates corroborate this change in BBB-GT expression in the brain anlage at the time of BBB maturation. However, low molecular weight glucose transporters, presumed to be of non-endothelial origin, are less dramatically reduced. The development of BBB tightness, therefore, seems to play a pivotal role in the pattern of BBB-GT expression during brain differentiation.

Animals↗

PubMed1986

Opening the blood-brain and blood-tumor barriers in experimental rat brain tumors: the effect of intracarotid hyperosmolar mannitol on capillary permeability and blood flow.

Using quantitative autoradiography, we investigated the effect of intracarotid infusions of hyperosmolar mannitol solutions on capillary permeability and blood flow. Capillary permeability, expressed in terms of a blood-to-tissue transfer constant (K), was determined in two rat brain tumor models by measuring the entry of 14C-alpha aminoisobutyric acid into brain tumor, into brain tissue adjacent to tumor, and into cortex. Cerebral blood flow was determined by measuring the uptake of 14C-iodoantipyrine in one rat brain tumor model. Blood flow was examined in the same regions as K, as well as in the corpus callosum. Before mannitol administration, K values in both Walker 256 (W256) carcinosarcoma and C6 gliomas were much higher than those in cortex. C6 gliomas were about three times more permeable than were W256 tumors. There was a direct correlation between tumor size and increased capillary permeability. Mannitol at a concentration of 1.37 M did not increase the K values for either tumor or adjacent tissue. At 1.6 M, mannitol increased the K values for both tumors (1.7-fold in C6 glioma and 13-fold in W256) as well as for adjacent tissue. At both concentrations, mannitol markedly increased cortical K values in all groups: by 48- to 72-fold at 1.37 M and by 90- to 105-fold at 1.6 M. The net effect of the mannitol was to reverse the tumor-to-cortex permeability relationship. Cortical blood flow increased modestly after intracarotid mannitol administration on both sides of the brain. These data provide little justification for using intracarotid mannitol during chemotherapy of human brain tumors.

Animals↗

PubMed2005

Enhanced chemotherapy delivery by intraarterial infusion and blood-brain barrier disruption in malignant brain tumors: the Sherbrooke experience.

BACKGROUND: The treatment of malignant brain tumors is hampered by the presence of the blood-brain barrier, which limits chemotherapy penetration to the central nervous system (CNS). In recent years, different strategies have been designed to circumvent this physiologic barrier. The osmotic blood-brain barrier disruption (BBBD) procedure is one such strategy, and has been studied extensively in preclinical and clinical studies. The authors detail their experience so far with the procedure in the context of an open Phase II study in the treatment of malignant brain tumors. METHODS: Patients with histologically proven malignant gliomas, primitive neuroectodermal tumors, primary CNS lymphomas, and metastatic disease to the brain were eligible. Patients enrolled were treated every 4 weeks (1 cycle) for < or = 12 cycles. A methotrexate-based regimen was offered to patients with lymphomas, whereas a carboplatin-based regimen was offered to patients with all other histologies. Before intraarterial chemotherapy infusion, patients were submitted to an osmotic BBBD procedure. RESULTS: Seventy-two patients were included in the current report. The overall median survival times (MST) from treatment initiation for glioblastoma multiforme (GBM), anaplastic oligodendrogliomas, primary CNS lymphomas, and metastases were, respectively, 9.1, 13.9, not reached, and 9.9 months, whereas time to disease progression was 4.1, 9.2, 12.3, and 3.3 months. The MST from diagnosis was 32.2 months for GBM. CONCLUSIONS: These encouraging results prompted the authors to further refine their knowledge of the potential contribution of this procedure in the treatment of brain tumors. These authors designed a randomized Phase III study for patients with GBM that is now open.

Adolescent↗

PubMed2003

Changes in cerebrovascular response during brain hypothermia after traumatic brain injury.

OBJECTIVE: Transcranial Doppler sonography (TCD) provides a rapid and noninvasive assessment of cerebral hemodynamics after traumatic brain injury. This study evaluates the change of cerebrovascular response at the rewarming stage of brain hypothermia using TCD. MATERIAL AND METHODS: Seventeen patients who had suffered from closed brain injury were investigated with daily TCD recordings and the changes in flow velocities were evaluated to determine whether they reflected the temperature during brain hypothermia. All patients who had treated brain hypothermia underwent continuous monitoring of SjO2, mean arterial blood pressure, and intracranial pressure (ICP). RESULTS: No significant changes in ICP and cerebral perfusion pressure (CPP) were recorded in all cases. Of 17 patients, 5 had a significant increase in SjO2 > 75% or more, retrospectively, with a robust increase in flow velocities of the middle cerebral artery (P < .01) at the rewarming stage. These cases marked a decrease in pulsatility index (P < .05) concomitant with an increase in SjO2 values. The CT scan revealed acute brain swelling in these cases. CONCLUSION: These data suggest cerebral vasoactivity could be altered at the rewarming stage. Hypothermia runs a risk of hyperemia at the rewarming stage, which induced a decrease in cerebral vasoresistance.

Acute Disease↗

PubMed1998

Molecular regulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived factors.

Glucose is the crucial metabolic fluid for the brain, and the transport of this nutrient from blood to brain is limited by the blood-brain barrier (BBB) GLUT1 glucose transporter. The activity of this transporter is altered in different pathophysiological conditions including Alzheimer's disease. The expression of the BBB-GLUT1 gene is directed by brain trophic factors, and the brain-derived peptide preparation Cerebrolysin (Cl, EBEWE, Austria), used in the treatment of Alzheimer's disease, increases the BBB-GLUT1 mRNA stability and the expression of the BBB-GLUT1 gene. In the present investigation, Cl markedly increased (p < 0.001) the expression of a BBB-GLUT1 reporter gene, named clone 753, that contains an important regulatory cis-acting element involved in the stabilization of this transcript in brain endothelial cultured cells (ECL). In experiments with a reporter gene lacking this regulatory element, Cl produced only a minimal fraction of the effect observed with clone 753. UV-cross linking/PAGE experiments showed that the GLUT1 transcript reacts with ECL cytosolic proteins to form a RNA/protein complex of approximately 80 kDa. The abundance of this cis/trans acting complex was found to be increased in Cl-treated cells. Overall, data presented here demonstrate that i) Cl increases the expression of a BBB-GLUT1-luciferase reporter gene containing a region of the 3'-untranslated region of BBB-GLUT1 mRNA with important regulatory cis-acting elements involved in the stabilization of this transcript, and ii) the increased expression of this BBB-GLUT1 reporter gene was associated with augmented abundance of a transacting factor that binds to the cis-acting element described in (i), suggesting that this association may be involved in the stabilization of GLUT1 mRNA induced by Cl.

3' Untranslated Regions↗

PubMed1990

Interaction between human brain tumour biopsies and fetal rat brain tissue in vitro.

The invasiveness of human intracranial tumours was studied in an organ culture system. Biopsies from six glioblastomas, four astrocytomas, two mixed gliomas, one ependymoma, four meningiomas and two carcinoma metastases were cut into fragments of 0.5 mm diameter, and placed in agar overlay tissue culture. The tumour specimens formed spheroids which were co-cultured with cell aggregates or fragments from fetal rat brain for up to 10 days in vitro. The invasiveness of the glioblastoma spheroids was characterised by a gradual destruction of normal brain tissue by tumour cells, followed by replacement of normal tissue by these cells. Co-cultures from two glioblastomas showed lesions in the normal brain tissue in areas removed from the tumour cells. Tumour spheroids from four glioblastomas totally destroyed the normal brain tissue without any change in the original tumour spheroid configuration. The low-grade gliomas were less invasive than the glioblastomas. The meningiomas and the metastases were non-invasive. This organ culture assay appeared to reflect the in situ invasive behaviour of the brain tumours examined. It is suggested that it may be used for evaluating the aggressiveness of individual brain tumours with the specific aim of correlating clinical data with the biological character of the tumour.

Adolescent↗