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Biomedical subjects

Martin Bendszus

Publications and source records attributed to Martin Bendszus.

At least 37 records · Page 2Linked to original sources
PubMed2004

Heparin and air filters reduce embolic events caused by intra-arterial cerebral angiography: a prospective, randomized trial.

BACKGROUND: Intra-arterial cerebral angiography is associated with a low risk for neurological complications, but clinically silent ischemic events after angiography have been seen in a substantial number of patients. METHODS AND RESULTS: In a prospective study, diffusion-weighted magnetic resonance imaging (DW-MRI) before and after intra-arterial cerebral angiography and transcranial Doppler sonography during angiography were used to evaluate the frequency of cerebral embolism. One hundred fifty diagnostic cerebral angiographies were randomized into 50 procedures, each using conventional angiographic technique, or systemic heparin treatment throughout the procedure, or air filters between the catheter and both the contrast medium syringe and the catheter flushing. There was no neurological complication during or after angiography. Overall, DW-MRI revealed 26 new ischemic lesions in 17 patients (11%). In the control group, 11 patients showed a total of 18 lesions. In the heparin group, 3 patients showed a total of 4 lesions. In the air filter group, 3 patients exhibited a total of 4 lesions. The reduced incidence of ischemic events in the heparin and air filter groups compared with the control group was significantly different (P=0.002). Transcranial Doppler sonography demonstrated a large number of microembolic signals that was significantly lower in the air filter group compared with the heparin and control groups (P<0.01), which did not differ from each other. CONCLUSIONS: Air filters and heparin both reduce the incidence of silent ischemic events detected by DW-MRI after intra-arterial cerebral angiography and can potentially lower clinically overt ischemic complications. This may apply to any intra-arterial angiographic procedure.

Adult↗
PubMed2004

Models for angiogenesis in gliomas.

During the last decades a lot of attention has been focussed on mechanisms of glioma vascularization, particularly in terms of investigating vascular growth factors and receptors. Recently, these efforts resulted in various approaches for antiangiogenic treatment strategies using in vitro cell culture systems as well as experimental orthotopic and non-orthotopic brain tumors. These basic science and preclinical trials need an assortment of models, which should allow investigating a variety of questions. Several objectives concerning basic endothelial cell (EC) characteristics can adequately be studied in vitro using EC monolayer assays. Three-dimensional spheroid techniques respect the more complex cell-cell and cell-environment interplay within a 3-dimensional culture. Recent advances in molecular genetic techniques offer a wide access to the genome of EC. Using these micro array or chip methods differences between micro- and macromolecular EC as well as variations within the gene pool of different organ specific EC can be assessed. To optimize the imitation of the crucial interaction of human gliomas with host endothelial cells, immunological cells and extracellular matrix, animal models are mandatory. An essential rule is to utilize an orthotopic model, since tumor-host-interaction is organ specific. To avoid alloimmunogenic responses, it is desirable to use weak or non-immunogenic glioma grafts, which is best accomplished in a syngeneic model. However, since rat gliomas poorly resemble human glioma growth patterns, human glioma xenografting into immunocompromized animals should be considered. In vivo-monitoring techniques like videoscopy via a cranial window or magnetic resonance imaging (MRI) allow for functional studies and improve the validity of the model employed. Finally, it is essentially to recognize the limitations of each model considered and to select that model which seems to be most appropriate for the objectives to be investigated.

Animals↗
PubMed2004

Muscle magnetic resonance imaging of denervation and reinnervation: correlation with electrophysiology and histology.

A signal increase in denervated muscle on magnetic resonance imaging (MRI) has been described in several clinical and experimental studies. Here, we studied the time course of T2-relaxation time changes in denervation and subsequent reinnervation in a rat model and correlated the findings with electrophysiology and quantitative histology. A prolongation of the T2 relaxation time in muscles was present 48 h after denervation, which was paralleled by spontaneous activity on electromyography (EMG). Histologically, there was a marked enlargement of the capillaries at that time point, indicating increased blood volume. The relaxation time changes peaked 3 weeks after beginning of nerve regeneration identified by EMG. Subsequently, the T2 prolongation normalized until 10 weeks after beginning of regeneration which was associated with a histological regression of the capillary enlargement. MRI closely mirrors the electrophysiological changes following denervation and reinnervation and may thus be used as adjunct to electrophysiology. The pathophysiological basis for the MR relaxation time changes is predominantly the enlargement of the capillary bed.

Animals↗
PubMed2004

MRI of peripheral nerve degeneration and regeneration: correlation with electrophysiology and histology.

Acute axonal nerve lesions cause a hyperintense signal on T2-weighted (T2-w) magnetic resonance imaging (MRI) at the nerve lesion site and distal to it. The aim of this experimental study was to investigate the spatiotemporal evolution and resolution of MR nerve signal changes following denervation and reinnervation, and to relate these findings to electrophysiology and histology. The proximal sciatic nerve of adult rats was ligated by a tight suture that was removed 1 week later to induce complete axotomy and nerve regeneration upon release. Serial electromyography (EMG) and motor nerve conduction studies were performed parallel to MRI at multiple points of time. Moreover, sciatic nerves were taken for quantitative histological evaluation. Nerve hyperintensity on T2-w MRI was present distal to the lesion at thigh level 24 h after denervation preceding the occurrence of spontaneous activity on EMG by 24 h. After 48 h, the entire sciatic nerve and its branches showed an increased signal down to the level of the lower leg. The increased nerve signal regressed with a proximo-distal gradient beginning from week 2 after onset of nerve regeneration in the thigh. On EMG, the first reinnervation potentials were detected at that time at the respective level. Compound muscle action potential (CMAP) in the foot muscle fully recovered 12 weeks after onset of nerve regeneration, that is, 2 weeks after resolution of the hyperintensity along the entire nerve on MRI. Histology revealed axonal degeneration in the acute phase and later nerve oedema parallel to the increased nerve signal on MRI. MR signal alterations occur as early as 24 h after an axonal nerve lesion and correlate with nerve fiber degeneration and later with nerve oedema on histology. MR findings in denervation and reinnervation parallel the electrophysiological changes. Thus, MRI is a promising diagnostic tool for the early detection of acute axonal nerve lesions and monitoring of nerve regeneration.

Animals↗
PubMed2004

Spontaneous regression of experimental gliomas--an immunohistochemical and MRI study of the C6 glioma spheroid implantation model.

OBJECTIVE: The orthotopic C6 glioma spheroid implantation model has been used to examine factors of neoangiogenesis, growth factor release, and protease expression as well the effect of antitumor agents. The present study systematically investigates the long-term course of orthotopically implanted C6 spheroid gliomas. METHODS: Reaggregated C6 spheroid tumors were implanted into the forebrain of 48 male Sprague-Dawley rats (32 immunocompetent, 16 thymectomized). The animals were examined by MRI at postoperative day (POD) 7, 14, 21, 28, 32, 45, 60, and 70. The MRI protocol included a T2-w and T1-w SE sequence before and after application of contrast medium and a CISS 3D sequence for volumetry. A total of six animals were selected after each MR exam from both groups and sacrificed for HE light microscopy and CD8+ T-lymphocyte, ED1+ macrophage, CD31+ endothelial cell immunohistochemistry. RESULTS: The tumors progressed to reach a maximum volume on day 28: 0.23 +/- 0.05 ml in the thymectomized and 0.16 +/- 0.021 ml in the immunocompetent group. Tumors then consistently regressed to vanish completely by POD 70. The influx of cytotoxic CD8+ T-lymphocytes correlated with tumor progression and the tumors reached a larger size in the thymectomized group. However, the time course of tumor regression was the same for both groups. CONCLUSION: The present data suggest that the orthotopic C6 glioma implanted into Sprague-Dawley rats will progress within a time span of approximately 4 weeks and can then retrogress again spontaneously. This finding has to be taken into account when deciding on a study protocol and the appropriate animal model. The C6 glioma model may be suitable to study the cell biological steps involved in the phenomenon of spontaneous tumor regression.

Animals↗
PubMed2004

In vivo monitoring of macrophage infiltration in experimental autoimmune neuritis by magnetic resonance imaging.

We report on the in vivo assessment of macrophage infiltration in adoptive transfer experimental autoimmune neuritis (AT-EAN), a prototypic Th-1-mediated autoimmune disorder of the peripheral nervous system (PNS). Lewis rats received systemic injections of superparamagnetic iron oxide (SPIO) particles at days 2, 3, 4, 5, or 9 after adoptive transfer of P2-specific T-cells and were scanned by standard 1.5 T magnetic resonance imaging (MRI) always 24 h later. MRI revealed focal signal loss of the cauda equina indicating iron accumulation in spinal nerves already at the preclinical stage (day 3). Signal loss peaked at day 4, when first clinical signs developed. At the maximum of clinical disease, signal loss already declined and disappeared on days 6 and 10. In spinal nerve sections, Perl's iron stain showed focal cellular accumulation of SPIO at days 3, 4, and 5 in ED1-positive macrophages. Spinal nerves at days 6 and 10 exhibited massive macrophage infiltrates, but no more iron deposition. In conclusion, SPIO-enhanced MRI provides a novel in vivo tool to assess the timing of macrophage entry into target tissues during an immunopathologic attack and holds promise to monitor immunotherapeutic interventions.

Animals↗
PubMed2004

Imaging of peripheral nerve lesions.

PURPOSE OF REVIEW: Clinical investigations of peripheral nerve lesions routinely involve nerve conduction studies and electromyography. Imaging studies are often used to exclude focal mass lesions or external compression and to visualize muscle atrophy. More recently, it has been recognized that magnetic resonance imaging can identify changes in peripheral nerves and secondary neurogenic alterations in skeletal muscle, which may significantly enhance its use in the differential diagnosis of peripheral nerve disease. RECENT FINDINGS: Acute axonal nerve lesions cause a hyperintense signal on T2-weighted images at and distal to the lesion site, which correlates with Wallerian degeneration and nerve oedema. Superparamagnetic iron oxide particles provide an exciting new tool to detect the invasion of macrophages into the degenerating nerve distal to an axonal lesion. Prolongation of the T2 relaxation time and gadolinium enhancement of denervated muscle develop in parallel to the development of spontaneous activity on electromyography, and are probably the consequence of capillary enlargement and increased muscular blood volume. SUMMARY: Magnetic resonance imaging supplements the differential diagnosis of peripheral nerve disease. An advantage over clinical neurophysiological investigations is that it is operator independent and painless. It can identify axonal damage and may thus help to identify a lesion site precisely, where fractionated nerve conduction studies are not applicable. Novel contrast media may potentially be used to detect pathophysiologically relevant mechanisms such as infiltration of the nerve by macrophages. Magnetic resonance imaging also has the advantage of providing a lasting detailed topographical picture of regional variations and avoids localization errors of muscles in electromyography.

Humans↗
PubMed2004

Neurophysiological monitoring, magnetic resonance imaging, and histological assays confirm the beneficial effects of moderate hypothermia after epidural focal mass lesion development in rodents.

OBJECTIVE: To assess the effects of moderate intraischemic hypothermia on neurophysiological parameters in an epidural balloon compression model in rats and to correlate the results with magnetic resonance imaging and histological findings. METHODS: Neurophysiological monitoring included laser Doppler flow, tissue partial oxygen pressure, and intracranial pressure measurements and electroencephalographic assessments during balloon expansion, sustained inflation, and reperfusion. Moderate intraischemic cooling of animals was extended throughout the reperfusion period, and results were compared with those for normothermic animals. Moreover, histological morphometric and magnetic resonance imaging volumetric analyses of the lesions were performed. RESULTS: Laser Doppler flow decreased slightly during ischemia (P < 0.05) in animals treated with hypothermia, and flow values demonstrated complete reperfusion, compared with incomplete flow restoration in untreated animals (P < 0.05). During ischemia, the tissue partial oxygen pressure was less than 4.3 mm Hg in both groups. After reperfusion, values returned to the normal range in both groups, but the tissue partial oxygen pressure in hypothermic animals was significantly higher (P = 0.042) and demonstrated 19% higher values, compared with normothermic animals, before rewarming. Moderate hypothermia attenuated a secondary increase in intracranial pressure (P < 0.05), and electroencephalographic findings indicated a trend toward faster recovery (P > 0.05) after reperfusion. Lesion size was reduced by 35% in magnetic resonance imaging volumetric evaluations and by 24.5% in histological morphometric analyses. CONCLUSION: Intraischemic hypothermia improves cerebral microcirculation, attenuates a secondary increase in intracranial pressure, facilitates electroencephalographic recovery, and reduces the lesion size.

Animals↗
PubMed2004

PTK787/ZK222584, an inhibitor of vascular endothelial growth factor receptor tyrosine kinases, decreases glioma growth and vascularization.

OBJECTIVE: The aim of this study was to test the efficacy of PTK787/ZK222584, an inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, on VEGF-dependent glioma vascularization and growth. METHODS: C6 rat glioma cells were transfected with VEGF(164) in a sense (V(+)) or antisense (V(-)) direction. Spheroids generated from V(+) or V(-) cells were implanted orthotopically into 60 rat brains. Expression of VEGF and fetal liver kinase-1 (VEGF receptor 2) was assessed immunohistochemically. Animals with V(+) gliomas received orally administered PTK787/ZK222584 on postoperative Day (POD) 1 to 12 or POD 7 to 12. Untreated animals served as negative controls, and animals with V(-) gliomas served as positive controls. Growth and vascularization were evaluated by magnetic resonance imaging and immunohistochemistry. RESULTS: Flk-1 expression was positive within tumor vessels in V(+) gliomas, whereas all C6 clones were negative for fetal liver kinase-1 in vitro. Early (POD 1-12) and delayed (POD 7-12) application of PTK787/ZK222584 in V(+) glioma-bearing animals resulted in a significant reduction of tumor size (71% and 36%, P < 0.05) as measured by magnetic resonance imaging volumetry. Early treated V(+) gliomas reached similar volumes compared with V(-) gliomas. Vessel density was significantly reduced (42.3% and 25.7%, P < 0.05), and areas of intratumoral necrosis were enlarged (by 1.7-fold after early treatment). Additionally, proliferation was decreased by 89% and 72% (P < 0.05). There was no growth-inhibiting effect of PTK787/ZK222584 on V(-) cells observed. CONCLUSION: PTK787/ZK222584 significantly halted VEGF-mediated glioma growth by inhibition of neovascularization and proliferation, providing a promising new tool in malignant glioma therapy.

Angiogenesis Inhibitors↗
PubMed2003

Caught in the act: in vivo mapping of macrophage infiltration in nerve injury by magnetic resonance imaging.

In vivo tracking of hematogenous macrophages has been a major challenge because these cells are key players in nerve injury and repair. We visualized the spatiotemporal course of macrophage infiltration after acute peripheral nerve injury in living rats by using superparamagnetic iron oxide (SPIO) particles and magnetic resonance imaging (MRI). A signal loss on MR images indicating iron accumulation was present in degenerating sciatic nerves between days 1 and 8 after a crush lesion, ceased thereafter, and corresponded to the transient presence of iron-labeled ED1-positive macrophages in tissue sections. In contrast, no SPIO accumulation was seen after optic nerve crush, which revealed microglial activation but lacked macrophage infiltration. SPIO-enhanced MRI provides a new tool to selectively visualize active periods of macrophage transmigration into the nervous system, thus enabling dynamic views on a fundamental process in a multitude of nerve disorders.

Animals↗
PubMed2003

Moderate hypothermia improves neurobehavioral deficits after an epidural focal mass lesion in rodents.

The objective of this study was to evaluate the effects of a moderate, intraischemic hypothermia on the behavorial deficits up to 4 weeks after induction of a focal mass lesion. A focal epidural mass lesion was induced by an epidural balloon. The severity of the trauma was defined by the balloon volume and flattening of electroencephalography. Hypothermia (32 degrees C) was induced as soon as maximum balloon infIation was reached. Ischemia was extended over 30 min. After reperfusion, normothermic (n = 24) and hypothermic animals (n = 25) were monitored for 3 h followed by a rewarming of the cooled animals. Results were compared to sham-operated animals (n = 10). Behavioral deficits were assessed by postural reflex (PR), open field (OF), beam balance (BB), beam walking (BW), and water maze tests (WMT). MRI follow-up and histology was evaluated. Sham-operated rats showed normal test results. Rats with normothermia showed worsening of test performance (PR, p < 0.05; OF, p < 0.05; BB, p < 0.05; BW, p < 0.05; WMT, p < 0.05) compared to controls over the whole observation period. A significantly better behavioral outcome was observed in animals treated with hypothermia which showed no differences from controls 3-4 days after injury (PR, OF, BB, BW, WMT, p > 0.05). Lesion induced mortality was reduced in cooled animals but overall mortality rates were not influenced by this therapeutic measure. Neuronal cell loss in the CA1-CA4 region (p < 0.05) was reduced and the lesion size smaller (21%/p > 0.05) in hypothermic animals. Magnetic resonance imaging revealed that the lesion was more pronounced in the cortical grey matter after normothermia, whereas hypothermic animals showed more subcortical brain lacerations. In conclusion, intraischemic hypothermia significantly improved the behavioral outcome, and decreased lesion-induced mortality and the size of the lesion after an epidural focal mass lesion.

Animals↗
PubMed2003

In vivo monitoring of macrophage infiltration in experimental ischemic brain lesions by magnetic resonance imaging.

Although macrophages represent the major inflammatory cells in cerebral ischemia, the kinetics of macrophage infiltration are largely unknown. To address this issue, we injected superparamagnetic iron oxide (SPIO) particles into the circulation of rats at different time points after focal photothrombotic cerebral infarction and performed magnetic resonance imaging (MRI) 24 hours later. Infarcts appeared as hyperintense lesions on T2-w and CISS MR images during all stages. At days 5.5 and 6, an additional rim of signal loss indicative of local accumulation of SPIO particles appeared at the outer margin of the hyperintense ischemic lesions, which was not present at days 1 to 5. Areas of signal loss corresponded to local accumulation of iron-loaded macrophages in histologic sections. At day 8, signal loss became restricted to the inner core of the lesions and ceased thereafter. Macrophages, however, were still present in late ischemic brain lesions, but they were iron-negative. Thus SPIO-induced signal loss indicates active macrophage transmigration into ischemic infarcts but not their mere presence. SPIO-induced signal loss was independent from the disturbance of the blood-brain barrier. In conclusion, we have shown by in vivo monitoring that macrophages enter photothrombotic infarcts at late stages of infarct development, suggesting a role in tissue remodeling rather than neuronal injury.

Animals↗
PubMed2003

MR imaging in the differential diagnosis of neurogenic foot drop.

BACKGROUND AND PURPOSE: Prolonged T2 relaxation time of denervated muscle has been described in several clinical and experimental studies. The purpose of this study was to evaluate the utility of MR imaging in the diagnosis of neurogenic muscle disorders compared with that of clinical and electrophysiologic examination. METHODS: In a prospective study, 40 consecutive patients clinically presenting with a foot drop were included. MR imaging of the lower leg included axial T1-weighted and axial turbo inversion recovery magnitude (TIRM) sequences. Two readers blinded to clinical data evaluated T1-weighted images for anatomic localization of affected muscles and TIRM images for patterns of signal intensity increase. After MR imaging, a detailed neurophysiologic examination was performed. Cause of foot drop was independently determined on the basis of MR and electrophysiologic data. RESULTS: Clinical examination and electromyography (EMG) disclosed 20 peroneal nerve lesions, nine cases of L5 radiculopathy, and 11 nerve lesions extending beyond neural structures. MR imaging revealed three distinct patterns of signal intensity increase on TIRM images: peroneal nerve pattern, L5 pattern, and unspecific pattern. MR imaging and EMG findings were in agreement in 37 (92%) of 40 patients. In three patients, MR imaging revealed a more widespread involvement than did EMG. In one of these patients, denervation in the corresponding muscle was validated by follow-up EMG. No false-negative diagnoses were made by use of MR imaging as compared with use of EMG. CONCLUSION: MR imaging improves accuracy in the differential diagnosis of peripheral nerve lesions compared with that of EMG and can supplement EMG in the diagnosis of denervated muscles.

Action Potentials↗