PubMed Health⌕ Search

Biomedical subjects

W Stummer

Publications and source records attributed to W Stummer.

36 records · Page 2Linked to original sources
PubMed1998

Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue.

Malignant gliomas accumulate fluorescing protoporphyrin IX intracellularly after exposure to 5-aminolevulinic acid, a metabolic precursor of haem. This phenomenon has been exploited for intraoperative identification of residual tumour to enable greater completeness of tumour removal. The present report describes the necessary modifications to the operating microscope to enable microsurgical, fluorescence-guided tumour removal. The system consists of a xenon light source coupled to the microscope, which can be switched from normal white light to violet-blue excitation light (375-440 nm). A longpass filter is introduced into the observer light path to enable observation of tumour fluorescence. Transmission characteristics of excitation and observation filters are chosen to transmit part of the remitted excitation light. Thereby the observer retains an impression of tissue detail, next to tumour porphyrin fluorescence. An integrating three chip CCD camera optimized for red light detection enables documentation of fluorescence findings. The present modifications allow uncomplicated and rapid recognition of red tumour fluorescence and its borders to normal tissue, without interrupting the course of the operation. Tissue detail is great enough to enable tumour resection under violet-blue excitation light during parts of the operation. The system appears to constitute a useful tool for optimizing removal of malignant gliomas on a routine basis.

Aminolevulinic Acid↗
PubMed1998

In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid.

Several malignant tissues synthesize endogenous porphyrins after exposure to 5-aminolevulinic acid (5-ALA). The present experiments have been designed to elucidate whether the C6 glioma cell, a model cell for human malignant glioma, similarly synthesizes porphyrins when exposed to 5-ALA, and whether specific synthesis occurs when C6 cells are inoculated into rat brains to form a tumor. In this situation the blood-brain barrier may interfere with 5-ALA availability, and spreading of porphyrins with edema outside the tumor may occur. Flow cytometry is used to determine the course of cell volume and porphyrin fluorescence intensities in cultured C6 cells which are incubated in 1 mM 5-ALA. For the induction of experimental brain tumors, 10(4) untreated C6 cells are inoculated into the brains of rats. After 9 days animals receive 100 mg 5-ALA/kg body weight. Brains are removed after 3, 6, or 9 h and frozen coronal sections obtained for H/E staining or fluorescence spectography. Cultured C6 cells show a linear increase of protoporphyrin IX fluorescence after exposure to 5-ALA, which begins to plateau after 85 min. Marked fluorescence is also observed in solid and infiltrating experimental tumor. However, faint fluorescence also occurs in normal tissue, basal pia, choroid plexus, and, more obviously, in white-matter tracts bordering the tumor (maximal distance: 1.5 +/- 0.7 mm). The observations demonstrate that C6 cells synthesize protoporphyrin IX after exposure to 5-ALA in vitro and in vivo. However, when utilizing 5-ALA for fluorescence detection or photodynamic therapy of brain tumors, attention should be paid to the possibility of protoporphyrin IX occurring outside the tumor.

Aminolevulinic Acid↗
PubMed1998

Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence.

OBJECTIVE: Survival after surgery and radiotherapy for the treatment of malignant gliomas is linked to the completeness of tumor removal. Therefore, methods that permit intraoperative identification of residual tumor tissue may be of benefit. In a preliminary investigation, we have studied the value of fluorescent porphyrins that accumulate in malignant tissue after administration of a precursor (5-aminolevulinic acid) for labeling of malignant gliomas in nine patients. METHODS: Three hours before the induction of anesthesia, 10 mg 5-aminolevulinic acid/kg body weight was administered orally. Intraoperatively, red porphyrin fluorescence was observed with a 455-nm long-pass filter after excitation with violet-blue (375-440 nm) xenon light and was verified by analysis of fluorescence spectra. Fluorescing and nonfluorescing samples taken from the tumor perimeters were examined histologically or used to study the photobleaching of porphyrins by excitation light and white light from the operating microscope. Plasma and erythrocyte porphyrin levels were determined by fluorescence photometry. RESULTS: Normal brain tissue revealed no porphyrin fluorescence, whereas tumor tissue was distinguished by bright red fluorescence. For a total of 89 tissue biopsies, sensitivity was 85% and specificity was 100% for the detection of malignant tissue. For seven of nine patients, visible porphyrin fluorescence led to further resection of the tumor. Under operating light conditions, fluorescence decayed to 36% in 25 minutes for violet-blue light and in 87 minutes for white light. Plasma and erythrocyte porphyrin contents increased slightly, without exceeding normal levels. CONCLUSION: Our observations suggest that 5-aminolevulinic acid-induced porphyrin fluorescence may label malignant gliomas safely and accurately enough to enhance the completeness of tumor removal.

Aged↗
PubMed1998

Terson's syndrome in subarachnoid hemorrhage and severe brain injury accompanied by acutely raised intracranial pressure.

OBJECT: The syndrome of retinal or vitreous hemorrhage in association with subarachnoid hemorrhage (SAH) is known as Terson's syndrome. The authors' purpose was to determine whether intraocular hemorrhage occurs with similar incidence when caused by severe brain injury accompanied by acutely raised intracranial pressure (ICP). METHODS: Prospective ophthalmological examination was performed in 22 consecutive patients with SAH or severe brain injury and elevated ICP. Thirteen patients were admitted for SAH (World Federation of Neurological Surgeons Grades II-IV) and nine for severe brain injury (Glasgow Coma Scale scores 3-10). Monitoring of ICP was performed at the time of admission via a ventricular catheter. Initial ICP exceeded 20 mm Hg in all patients. Indirect ophthalmoscopy without induced mydriasis was performed within the 1st week after the acute event. Retinal or vitreous hemorrhage was seen in six (46%) of 13 patients with SAH and in four (44%) of nine patients with severe brain injury. Ocular bleeding was found bilaterally in three patients with SAH and in one patient with severe brain injury (18%). Six of the 10 patients with Terson's syndrome died as a result of their acute event. CONCLUSIONS: The present results indicate that Terson's syndrome may be related to acute elevation of ICP, independent of its causes, and may occur with similar incidence in patients with severe brain injury and those with SAH. Because recognition and treatment of Terson's syndrome may prevent visual impairment and associated secondary damage to the eye, increased awareness of this entity in all patients with acute raised intracranial hypertension is recommended.

Acute Disease↗
PubMed1997

The effects of hypo- and hyperkalemia on choroid plexus potassium transport.

To examine the mechanisms involved in cerebrospinal fluid (CSF) K+ homeostasis, lateral ventricle choroid plexuses were isolated from rats fed low, normal or high K+ diets for 2 weeks. Potassium (86Rb) influx and efflux were then examined in vitro. Dietary hypo- and hyperkalemia (2.8 +/- 0.1 and 6.8 +/- 0.3 mM) did not affect the efflux rate constant for 86Rb or the influx rate constant in the absence of inhibitors. However, the ouabain-sensitive portion of influx was only 1.9 +/- 0.5 microl/g per min in plexuses from hypokalemic rats compared to 4.5 +/- 0.5 microl/g/min in controls (P < 0.001). This change in Na+/K+-ATPase activity was reflected in an increasing amount (Western blot) of the alpha1 and beta1 subunits of this pump with increasing plasma K+ concentration (P < 0.05) whereas the beta2 subunit was unaffected. The other known choroid plexus K+ uptake mechanism, bumetanide-sensitive K+ cotransport, was unaffected by dietary K+ manipulation. In normo- and hyperkalemic rats, the sum of the ouabain- and bumetanide-sensitive fluxes could account for all of 86Rb uptake. However, in hypokalemic rats a major component (40%) of uptake could not be accounted for by either mechanism. This unidentified mechanism may be a basolateral uptake mechanism involved in increasing K+ transport from blood to CSF during hypokalemia.

Animals↗
PubMed1997

Leukocyte-endothelium interactions in global cerebral ischemia.

A closed cranial window was implanted in male Mongolian Gerbils to investigate leukocyte-endothelium interactions (LEI) at the brain surface in global cerebral ischemia (GCI) by intravital fluorescence microscopy. Four days after 15 min of bilateral common carotid artery occlusion the ischemic tissue damage was histologically analysed in selectively vulnerable areas of the brain. The frequency of Rhodamine 6G labeled leukocytes rolling along ("roller") and firmly attached ("sticker") to postcapillary endothelium was assessed before and up to 180 min after GCI. As compared to the sham operated control animals induction of LEI was found in animals with GCI, following a steady increase up to a significant level attained at 60 min (rollers) or at 120 min of reperfusion (sticker), respectively (p < 0.05). In animals with cerebral ischemia histological assessment revealed a significant decrease of viable neurons in the CA1-sector of hippocampus (neurons/mm2 +/- SEM: 1308 +/- 71 vs. 829 +/- 106), in parietal neocortex (727 +/- 17 vs. 542 +/- 49), and in striatum (547 +/- 26 vs. 352 +/- 49; p < 0.01), respectively. A significant correlation between the extent of irreversible neuronal damage and the frequency of leukocyte adherence to the endothelium could not be established. Nevertheless a direct correlation between the number of surviving neurons and of rolling leukocytes was observed, which may be suggestive of a protective potential of leukocyte rolling.

Animals↗
PubMed1996

Cerebral lactate production in relation to intracranial pressure, cranial computed tomography findings, and outcome in patients with severe head injury.

Severe head injury is frequently associated with focal or global disturbances of cerebral blood flow and metabolism. Routine monitoring of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in these patients does not provide information about critically reduced local or global cerebral blood flow. Measurements of cerebral lactate difference, Lactate-Oxygen-Index (LOI) and cerebral oxygen extraction were evaluated for advanced monitoring by comparing these parameters with ICP, cranial computed tomography (CCT) findings, and outcome in a group of severely head-injured patients. In 21 patients with severe brain trauma (GCS < or = 8), arterial as well as jugular venous lactate levels and oxygen saturation were measured in vitro every 6 h after admission of patients to the intensive care unit (ICU) throughout the acute course of treatment. Arterial blood pressure, blood gases, and ICP were assessed by standard monitoring measurements. CCT was performed initially after admission of the patients to the hospital, during the acute period in the ICU, if indicated, and 10 to 14 days after trauma. Outcome was classified according to the Glasgow outcome scale (GOS) at six months after injury. Data were averaged in each patient for every day after trauma and over the entire monitoring period. Resulting values were tested for correlation by regression analysis. Additionally, the data of the group of patients with normal to minimally elevated mean ICP (ICP < 20 mmHg, n = 12) were compared to those of the patients with increased mean ICP (ICP > 20 mmHg, n = 9). The cerebral lactate difference in all patients on the day of trauma was significantly increased as compared to the later period (0.20 vs. 0.11-0.07 mmol/l, p < 0.05), but was not different with high or normal to minimally elevated ICP. In patients with intracranial hypertension, the cerebral lactate difference remained significantly increased from the first to the fifth day after injury, whereas it normalized in this period in the group with normal to minimally elevated ICP. Averaged over the acute course, patients with increased ICP had significantly higher mean lactate differences (0.18 +/- 0.16 vs. 0.067 +/- 0.025 mmol/l, p = 0.001) and higher mean LOIs (0.072 +/- 0.071 vs. 0.028 +/- 0.013, p = 0.011). There was a significant correlation of increased mean cerebral lactate difference to poor outcome (r = 0.46, p = 0.035). Cerebral oxygen extraction in all patients tended to increase on the day of trauma (36.7% vs. 29.2% to 31.5% during the subsequent course), but this difference was not significant. The initial degree of brain swelling, classified by CCT according to Marshall et al. (1991), showed no correlation with cerebral lactate differences, ICP, O2-extraction, or outcome. Neither was there a correlation of cerebral oxygen extraction to ICP nor to outcome. In conclusion, the severity of brain trauma and outcome of patients was reflected by increased cerebral lactate production. Unchanged values of global cerebral oxygen extraction suggest that the regulatory mechanisms of brain oxygen supply were not impaired by trauma. Measurements of cerebral lactate differences and brain oxygen extraction may contribute to advanced monitoring in severe head injury.

Adolescent↗
PubMed1996

Photodynamic therapy within edematous brain tissue: considerations on sensitizer dose and time point of laser irradiation.

Photosensitizer is known to spread with vasogenic edema fluid arising from a cerebral lesion (Neurosurg 33:1075-1082, 1993), which may be essential for sensitizing malignant cells outside the main tumor mass. The present experiments seek to elucidate whether resultant necrosis of perifocal brain tissue after laser irradiation follows a corresponding time pattern and whether damage depends on the photosensitizer dose. Male Wistar rats were anaesthetized with chloralhydrate for venous cannulation, craniotomy and focal cold lesion in order to induce vasogenic edema. Simultaneously, Photofrin II (PF II) was administered at a dose of 5 mg kg-1. The animals were re-anaesthetized after either 4, 12 or 24 h for the irradiation of lesion and perifocal tissue with 200 J cm-2 of laser light (630 nm). The brains of other animals were irradiated 4 h after cold lesion with 200 J cm-2 after receiving either 0, 2.5 or 5 mg kg-1 PF II (all groups: n = 6). Resultant necrosis was assessed planimetrically in serial coronal cryosections of brains perfusion fixed 24 h after irradiation. Necrosis was significantly enhanced with irradiation 4 h after cold lesion and photosensitizer (avg. area +/- SD: 4.3 +/- 0.7 mm2) compared with lesion only (0.84 +/- 0.2 mm2). Maximal necrosis (6.3 +/- 1.6 mm2) occurred with irradiation 12 h after lesion, whereas necrosis was only slightly increased with irradiation at 24 h (2.8 +/- 0.4 mm2). Furthermore, the area of necrosis was dependent on the sensitizer dose (0 mg kg-1: 0.7 +/- 0.3 mm2, 2.5 mg kg-1: 2.09 +/- 0.2 mm2, 5 mg kg-1: 4.3 +/- 0.7 mm2; all differences p < 0.05). Therefore, to prevent unwanted side-effects such as necrosis of edematous but otherwise healthy, peritumoral tissue in the treatment of malignant cerebral tumors by PDT, tribute should be paid to the possibility of time and dose dependent sensitization of the perifocal tissue after i.v. administration of photosensitizer.

Animals↗
PubMed1996

Evidence for peroxidative damage by nitric oxide in experimental chronic cerebral vasospasm.

Recent data has suggested a role for the nitric oxide metabolite peroxynitrite in peroxidative injury to endothelium associated with atherosclerosis. The present experiments were designed to elucidate whether such a mechanism might be involved in the morphological changes observed during chronic vasospasm after subarachnoid hemorrhage. For this purpose, chronic vasospasm was induced in male Wistar rats by an injection of autologous blood (100 microliters) in the cisterna magna followed by a second injection 24 hours later. Vasospasm was verified by pressure controlled internal carotid angiography after retrograde cannulation of the external carotid artery 7 days after the second injection. Animals were then perfusion fixed and the brains removed for immunohistochemical assessment of nitrotyrosine, the peroxidation product of peroxynitrite with tyrosine contained in tissue proteins. Staining for nitrotyrosine was quantified by microscopy in 40 microns coronal floating sections. The brains of rats with angiographic vasospasm revealed nitrotyrosine predominantly located with a perivascular distribution and in the pia. We conclude that peroxidation of membrane proteins by the nitric oxide metabolite peroxynitrite may contribute to the morphological damage evident in chronic vasospasm.

Animals↗
PubMed1995

Blood-brain barrier taurine transport during osmotic stress and in focal cerebral ischemia.

Little is known about blood to brain taurine transport despite substantial evidence suggesting a role of taurine in brain volume regulation during osmotic stress or conditions inducing cell swelling, such as ischemia. We have made measurements of the taurine influx rate constant (K1) with [3H]taurine in three conditions: raised plasma taurine concentrations induced by infusion with 50 mM taurine (10 microliters/100 g/min); osmotic stress induced by i.p. injections of 1.5 M NaCl (2 ml/100 g) or distilled water (10 ml/100 g); and 4 h of middle cerebral artery occlusion (MCAo). In rats with MCAo, additional determinations were made of tissue water and taurine contents, and blood-brain barrier passive permeability with [3H]alpha-aminoisobutyric acid. Taurine infusion increased plasma taurine from 110 +/- 63 microM (SD) to 407 +/- 63 (p < 0.001) and decreased taurine K1 at the blood-brain barrier by 70% (p < 0.001), signifying saturable uptake that maintained unidirectional influx constant. Similarly, although hypo- and hyperosmolality increased and decreased plasma taurine concentration, respectively, a reciprocal relationship between K1 and plasma taurine in these experiments ensured that unidirectional fluxes of taurine into brain were unchanged by osmotic stress. During MCAo, the taurine K1 was reduced 80% in the ipsilateral ischemic tissue compared with the contralateral nonischemic tissue (p < 0.001). This decline may be due to a release of taurine into the brain circulation, because there was a concomitant loss of tissue taurine of 7.4 +/- 2.4 mmol/g dry weight (p < 0.05). Alternately, if taurine uptake is sodium dependent, the decline might reflect a disruption of the endothelial sodium gradient.

Aminoisobutyric Acids↗
PubMed1995

Mechanisms of brain ion homeostasis during acute and chronic variations of plasma potassium.

Brain and CSF potassium concentrations are well regulated during acute and chronic alterations of plasma potassium. In a previous study, we have shown that during chronic perturbations, regulation is achieved by appropriate adaptation of potassium influx, but that the degree of such adaptation during acute perturbations is much less. To elucidate further potential regulatory mechanisms, rats were rendered acutely or chronically hyper- or hypokalemic (range 2.7-7.6 mM). Measurements were made of brain and CSF water and ion contents to examine whether regulation occurred by modulation of K+ uptake into parenchymal cells. Furthermore, the permeability-surface area products (PSs) of 22Na+ were determined, because changes in K+ efflux fia Na+,K(+)-ATPase on the brain-facing side of the blood-brain barrier might be reflected in modified Na+ permeability. Brain and CSF K+ concentrations and Na PS were all independent of chronic changes in plasma K+ and acute hypokalemia, suggesting that neither modulation of parenchymal K+ uptake nor K+ efflux via the Na+,K(+)-ATPase is involved in extracellular K+ regulation in these conditions. In contrast, Na PSs were increased by 40% (p < 0.05) in acute hyperkalemia. This was accompanied by a slight loss of tissue K+ and water from the intracellular space. These results suggest that increased potassium influx in acute hyperkalemia is compensated by stimulation of K+ efflux via Na+,K(+)-ATPase. A slight degree of overstimulation, as indicated by a net loss of tissue K+, leads us to hypothesize that other factors, apart from the kinetic characteristics of Na+,K(+)-ATPase, may regulate this enzyme at the blood-brain barrier.

Animals↗
PubMed1995

Cerebral protection against ischemia by locomotor activity in gerbils. Underlying mechanisms.

BACKGROUND AND PURPOSE: A previous communication of this laboratory demonstrated reduced mortality and neuronal damage by spontaneous locomotor activity preceding forebrain ischemia in Mongolian gerbils. The present experiments seek to elucidate potential mechanisms of protection by measurement of cerebral blood flow, cerebral tissue conductance as an indicator of ischemic cell swelling, and the cerebral release of eicosanoids. METHODS: Gerbils were maintained either in conventional cages (nonrunners) or with free access to running wheels (runners) for 2 weeks preceding 15 minutes of forebrain ischemia. During ischemia and 2.5 hours of reperfusion, cerebral tissue conductance was determined with a two-electrode system. Simultaneously, prostaglandin D2, prostaglandin F2 alpha, and thromboxane B2 were measured in ventriculocisternal perfusate. In additional animals cerebral blood flow was assessed by hydrogen clearance. RESULTS: Decreases in tissue conductance during ischemia were similar in nonrunners (56 +/- 3%) and runners (62 +/- 3%) but normalized more rapidly in runners during reperfusion. In both groups reperfusion was accompanied by marked increases of perfusate prostaglandin D2, prostaglandin F2 alpha, and thromboxane B2. In nonrunners, however, thromboxane B2 was already elevated during ischemia (147 +/- 9%, P < .01) and remained elevated longer during recirculation (P < .05). Postischemic perfusion maxima were higher in runners (70.8 +/- 7.4 versus 47.0 +/- 5.0 mL/100 g per minute, P < .05) and were observed sooner (27.4 +/- 6.9 versus 62.2 +/- 12.3 minutes, P < .05). Both groups displayed delayed hypoperfusion of a similar magnitude (runners, 29.0 +/- 2.4 mL/100 g per minute; nonrunners, 30.1 +/- 2.4 mL/100 g per minute). CONCLUSIONS: Protection by preischemic locomotor activity may involve enhanced postischemic reperfusion, leading to more rapid normalization of conductance and thus of cell volume. Enhanced reperfusion may be the consequence of attenuated thromboxane liberation during and after ischemia.

Animals↗
PubMed1994

Rubidium entry into brain and cerebrospinal fluid during acute and chronic alterations in plasma potassium.

To elucidate whether K+ uptake across the blood-brain barrier (BBB) or blood-cerebrospinal fluid (CSF) barrier is subject to acute or chronic regulation, rats were rendered acutely or chronically hyper- or hypokalemic (range: 2.8-7.2 mM). Measurements were made of the permeability-surface (PS) products of 86Rb+, a marker for K+, and alpha-[3H]aminoisobutyric acid (AIB), a passive permeability marker, and of CSF K+ concentration ([K+]CSF). [K+]CSF decreased by 8% in chronic hypokalemia P < 0.01), but otherwise remained unchanged. The AIB PS products were unaltered in any group, excluding a change in passive permeability. The Rb PS product, however, increased by 31% for brain tissue (P < 0.01) and by 46% for CSF (P < 0.05) during acute hypokalemia, but was unchanged during acute hyperkalemia. During chronic hypokalemia the Rb PS product increased by 40% for brain (P < 0.01) and 55% for CSF (P < 0.01) and decreased during chronic hyperkalemia by 37% for brain (P < 0.01) and 49% (P < 0.01) for CSF. Unidirectional K+ fluxes were calculated, revealing greater regulation of K+ influx into both brain tissue and CSF during chronic compared with acute changes of plasma K+ concentration ([K+]pl). Our results suggest that K+ transport is saturable at both the BBB and the blood-CSF barriers under normal conditions and that both barriers adapt to chronic changes in [K+]pl by modifying specific, transcellular routes of K+ entry.

Aminoisobutyric Acids↗
PubMed1994

Reduced mortality and brain damage after locomotor activity in gerbil forebrain ischemia.

BACKGROUND AND PURPOSE: Preischemic spontaneous locomotor activity was distinguished in this laboratory as a factor influencing outcome after 15 and 20 minutes of forebrain ischemia in gerbils. Histological investigations were carried out to analyze potential relations between postischemic survival and a reduction of cerebral damage by spontaneous locomotor activity. METHODS: Male Mongolian gerbils were divided into two groups, one with access to running wheels ("runners") and one kept in conventional cages ("nonrunners") for 2 weeks preceding forebrain ischemia of 15 or 20 minutes. A total of 99 gerbils were divided in subgroups and were allowed to recover for 2 weeks for assessment of survival. Other subgroups (n = 7 to 9) were killed at day 4 for quantitative histology of selectively vulnerable areas such as hippocampus, cortex, striatum, and thalamus. RESULTS: Two weeks after 15-minute ischemia, 44% of non-runners had survived compared with 90% of runners (P < .01). With 20-minute ischemia all runners survived compared with 21% of nonrunners. Quantitative histology (15-minute ischemia) revealed selective nerve cell injury in various cerebral regions in both groups. In runners, however, with the exception of the CA1 sector, damage was attenuated in cortex, striatum, and hippocampus. Furthermore, the extent of thalamic infarction was reduced (P < .05). CONCLUSIONS: Locomotor activity before global cerebral ischemia is highly efficient in protecting the brain as demonstrated by enhanced survival and a reduction of tissue damage in Mongolian gerbils. The mechanisms underlying this protection are currently unclear. However, further understanding of this intriguing phenomenon should enhance the understanding of ischemia pathophysiology and lead to the development of new treatment strategies.

Animals↗
PubMed1993

Kinetics of Photofrin II in perifocal brain edema.

Photodynamic therapy is under intense investigation as a possible adjuvant for the treatment of malignant tumors of the central nervous system. It relies on the fact that photosensitizers are selectively taken up or retained by malignant tissue. However, most brain tumors are accompanied by substantial vasogenic edema as a consequence of blood-brain barrier disruption within the tumor, leading to extravasation and propagation of plasma constituents into the surrounding brain tissue. Systemically administered photosensitizers may enter healthy tissue together with the edema fluid, possibly leading to sensitization of tissues outside the tumor. To test this hypothesis, vasogenic edema was induced by cold injury to the cortex in rats. The edema thus obtained is highly reproducible and very similar to tumor-associated edema. Just after injury induction, Photofrin II (PF-II), a commonly used photosensitizing agent, was administered at a dose of 5 mg per kilogram of body weight along with fluorescein isothiocyanate (FITC)-labeled albumin to mark edema advancement. After 1, 4, 12, or 24 hours, the brains were removed and frozen, and cryosections were studied with high-sensitivity video fluorescence microscopy for edema extravasation within the lesion and propagation of PF-II into the surrounding gray matter. PF-II advanced with edema along the corpus callosum underlying the cortex to a distance of 5 mm from the lesion after 4 hours. With the exception of the lesion, PF-II fluorescence returned to baseline after 24 hours, indicating subsequent washout. Propagation was comparable to the spreading of FITC-marked albumin. The authors conclude that photosensitizers spread with edema, an observation that may be pertinent to a number of questions concerning photodynamic therapy of cerebral tumors.

Animals↗
PubMed1990

Electrical impedance, rCBF, survival and histology in Mongolian gerbils with forebrain ischaemia.

Survival, quantitative morphology of the hippocampus, cerebral tissue impedance and regional cerebral blood flow (rCBF) were studied in the Mongolian gerbil after 15 minutes of bilateral common carotid occlusion. A subgroup of animals was placed in cages with free access to running-wheels for two weeks preceding ischaemia to measure voluntary locomotor activity. Survival was enhanced in the running-wheel subgroup, with 90% of the animals still alive after 14 days as compared to 48% of the non-running group. Neuronal loss was found in all animals in the hippocampus (CA1, CA2, CA3 and CA4), and was most pronounced in the CA1 sector. In the running-wheel group, however, neuronal loss was significantly lower in sectors CA2, CA3 and CA4. The increases of cerebral impedance, which indicate ischaemic cell swelling, reached 190% in both groups during ischaemia. During postischaemic recirculation, however, impedance normalized more rapidly in the running-wheel group, indicating earlier resolution of ischaemic cell swelling. In wheel-running gerbils, postischaemic hyperperfusion evolved earlier and was more pronounced as compared to non-runners. No differences in systemic blood pressure were observed during cerebral ischaemia or thereafter.

Animals↗
PubMedDate not supplied

Measuring the angular dependent energy distribution of backscattered electrons at variable geometry.

An aluminium semisphere system with 120 points of entry and eight detection areas, assembled on a meridian covering 0.0026 steradian each, was put over a solid bulk sample (e.g., aluminium), which was mounted in the eucentric point so that the incident electron beam could be varied by a polar rotation of the sphere in steps of 11.25 degrees. The complete angular distribution of the backscattered electrons became available by a rotation in steps of 11.25 degrees azimuthally. For this particular setup, the signals from the detection areas as well as the signal from the rest of the semisphere were amplified by operational amplifiers (Burr-Brown OPA128LM). However the signal of the semisphere was not available at that time. Specimen current measurements made the total amount of electrons accessible, providing a possibility for normalization of the results and comparison with total backscattering coefficients. By use of counter voltage variable up to 10 kV inside the detection assembly, it was possible to measure an energy resolution of the backscattered electrons for each detection area at the same time. Details of the construction and calibration procedures, possible errors, and sources of systematic deviations as well as first test results are discussed.

Journal Article↗