Comparison of low energy and high energy electron beam treatments on sensory and chemical properties of seeds.

Consumption of fresh and minimally processed foods such as seeds as a part of a healthy diet is a trend. Unfortunately, fat-rich seeds are often contaminated with pathogenic microorganisms and face frequent product recalls. Electron beams have been applied as a microbial decontamination measure for decades. Conventionally high energy electron beams (HEEB) are being used, whereas low energy electron beams (LEEB, <300 keV) have only recently been introduced to the food industry and more studies are needed. Electron beam treatment has several advantages over other decontamination technologies. The treatment is non-thermal, chemical-free, water-free, and does not use radioactive substances. The effect of electron beams on the sensory and chemical properties of seeds has not been widely studied. This study assessed LEEB and HEEB treated pumpkin and flax seeds immediately after treatments, and after three months of storage. The seeds' sensory profiles were altered after both treatments when compared with non-treated samples, with a higher dose leading to a greater level of alteration. However, the sensory profile of LEEB treated seeds was similar to the non-treated seeds whereas HEEB treated seeds differed from both. The storage period of three months further increased the observed differences between the samples. LEEB and HEEB treatments seemed to cause lipid degradation as the content of volatile aldehydes was increased. This effect was more profound in HEEB treated samples. The data presented in this study shows that LEEB as a microbial reduction solution has great potential to preserve the chemical and sensory properties of nutritious seeds.

Pathoarchitectonics of the cerebral cortex in chorea-acanthocytosis and Huntington's disease.

AIMS: Quantitative estimation of cortical neurone loss in cases with chorea-acanthocytosis (ChAc) and its impact on laminar composition. METHODS: We used unbiased stereological tools to estimate the degree of cortical pathology in serial gallocyanin-stained brain sections through the complete hemispheres of three subjects with genetically verified ChAc and a range of disease durations. We compared these results with our previous data of five Huntington's disease (HD) and five control cases. Pathoarchitectonic changes were exemplarily documented in TE1 of a 61-year-old female HD-, a 60-year-old female control case, and ChAc3. RESULTS: Macroscopically, the cortical volume of our ChAc cases (ChAc1-3) remained close to normal. However, the average number of neurones was reduced by 46% in ChAc and by 33% in HD (P = 0.03 for ChAc & HD vs. controls; P = 0.64 for ChAc vs. HD). Terminal HD cases featured selective laminar neurone loss with pallor of layers III, V and VIa, a high density of small, pale, closely packed radial fibres in deep cortical layers VI and V, shrinkage, and chromophilia of subcortical white matter. In ChAc, pronounced diffuse astrogliosis blurred the laminar borders, thus masking the complete and partial loss of pyramidal cells in layer IIIc and of neurones in layers III, V and VI. CONCLUSION: ChAc is a neurodegenerative disease with distinct cortical neurodegeneration. The hypertrophy of the peripheral neuropil space of minicolumns with coarse vertical striation was characteristic of ChAc. The role of astroglia in the pathogenesis of this disorder remains to be elucidated.

Influence of hydrothermal treatment on the structural modification of spent grain specific carbohydrates and the formation of degradation products using model compounds.

Brewer's spent grain (BSG) constitutes various valuable carbohydrates that may contribute to a healthy diet. These components may be obtained from BSG via hydrothermal treatment (HT), a procedure for dissolving water-inextricable carbohydrates. The objective of this study was to investigate HT as an environmentally friendly technology for extracting high-molecular-weight fiber with proven beneficial effects on human health. Cellulose, ß-glucan, and arabinoxylan (AX) served as model substances and were subjected to auto-hydrolysis at different temperatures and reaction times. The results were evaluated in terms of structural and chemical characteristics. When the treatment temperature was increased, the original weight-average molar mass of AX (370 kDa) and ß-glucan (248 kDa) decreased gradually (<10 kDa), and the molar mass distribution narrowed. Further investigations focused on the heat-induced formation and elimination of monosaccharides and undesirable by-products. The concentrations of by-products were successfully described by kinetic models that can be used to optimize the hydrolysis process.

Damping by slow relaxing rare earth impurities in Ni80Fe20.

Doping Ni80Fe20 by heavy rare earth atoms alters the magnetic relaxation properties of this material drastically. We show that this effect can be well explained by the slow relaxing impurity mechanism. This process is a consequence of the anisotropy of the on site exchange interaction between the 4f magnetic moments and the conduction band. As expected from this model the magnitude of the damping effect scales with the anisotropy of the exchange interaction and increases by an order of magnitude at low temperatures. In addition, our measurements allow us to determine the relaxation time of the 4f electrons as a function of temperature.

Laser-induced magnetization dynamics of lanthanide-doped permalloy thin films.

We investigate the effect of Ho, Dy, Tb, and Gd impurities on the femtosecond laser-induced magnetization dynamics of thin Permalloy films using the time-resolved magneto-optical Kerr effect. Varying the amount of Ho, Dy, Tb content from 0% to 8%, we observe a gradual change of the characteristic demagnetization time constant from approximately 60 to approximately 150 fs. In contrast, Gd concentrations up to 15% do not influence the time scale of the initial photoinduced magnetization loss. We propose a demagnetization mechanism that relies on strong magnetic inertia of the rare-earth dopant which stabilizes the ferrimagnetic ordering and thereby delays the demagnetization.

Effect of brain-derived neurotrophic factor treatment and forced arm use on functional motor recovery after small cortical ischemia.

BACKGROUND AND PURPOSE: Both the administration of growth factors and physical therapy such as forced arm use (FAU) are promising approaches to enhance recovery after stroke. We explored the effects of these therapies on behavioral recovery and molecular markers of regeneration after experimental ischemia. METHODS: Rats were subjected to photothrombotic ischemia: sham (no ischemia), control (ischemia), brain-derived neurotrophic factor (BDNF; ischemia plus BDNF, 20 microg), and FAU (ischemia plus FAU, 1-sleeve plaster cast ipsilateral limb). Animals survived 1 or 6 weeks and underwent behavioral testing (Rotarod, beam balance, adhesive removal, plantar test, neuroscore). After the rats were killed, brain sections were immunostained for semiquantitative analysis of MAP1B, MAP2, synaptophysin, GFAP expression, and quantification of infarct volumes. RESULTS: Infarct volumes were not different between the groups 1 or 6 weeks after ischemia. BDNF-treated animals had better functional motor recovery (Rotarod, beam balance, neuroscore) compared with all other groups (P<0.05). There was no significant adverse effect of early FAU treatment on motor recovery, although sensorimotor function (adhesive removal test) was impaired (P<0.05). There were no differences between groups as measured by nociception of the left and right forepaw (plantar test). BDNF treatment transiently induced MAP1B expression in the ischemic border zone and synaptophysin expression within the contralateral cortex 6 weeks after ischemia (P<0.05). Both BDNF and FAU reduced astrogliosis compared with controls (P<0.05). CONCLUSIONS: Postischemic intravenous BDNF treatment improves functional motor recovery after photothrombotic stroke and induces widespread neuronal remodeling. Early FAU treatment after stroke does not increase infarct size, impairs sensorimotor function, but leaves motor function unchanged. Postischemic astrogliosis was reduced by both treatments.

Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene.

We report a Turkish family with parental consanguinity and at risk for sialidosis type II, an inherited autosomal recessive disorder caused by lysosomal alpha-N-acetyl-neuraminidase (sialidase, NEU1) deficiency. The proband was a premature male infant that presented with hydrops, hepatomegaly, respiratory distress syndrome, and anemia and that died of respiratory insufficiency 2 months after birth despite intensive care. An abnormally increased [14C]methylamine incorporation and an isolated deficiency of lysosomal alpha-N-acetyl-neuraminidase were found in cultured skin fibroblasts. A previous pregnancy of the mother terminated in a spontaneous abortion in the 13th week of gestation. A successive pregnancy showed hydrops fetalis, and an enzymatic assay of cultured amniotic fluid cells indicated a deficiency of alpha-N-acetyl-neuraminidase. Following pregnancy termination at 20 weeks gestation, light microscopy of fetal tissues revealed classic vacuolation not only in liver, bone marrow, brain, and kidney, but also in endocrine organs such as the thyroid gland, adrenal gland, hypophysis, and testes, and in the thymus. DNA analysis of the family showed that both the proband and the third sibling had a novel homozygous nonsense point mutation at nucleotide 87 in exon 1 of the alpha-N-acetyl-neuraminidase (neu1) gene causing a substitution of tryptophan at codon 29 by a termination codon (W29X). DNA sequencing of polymerase chain reaction products identified the parents as heterozygous carriers. To detect neu1 mRNA expression, a real-time reverse transcription/polymerase chain reaction was performed, and similar rates of neu1 mRNA expression were found in the fibroblasts of the fetus, the 2nd sibling, and in controls. The very early termination codon with complete loss of neuraminidase activity is probably the molecular basis of the unusually severe vacuolation pattern in this form of congenital sialidosis.

Kainate-induced epilepsy alters protein expression of AMPA receptor subunits GluR1, GluR2 and AMPA receptor binding protein in the rat hippocampus.

Kainic acid induces seizures with consecutive degeneration of highly vulnerable hippocampal CA3 neurons in adult rats. An abnormal influx of calcium through newly synthesized alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptors lacking the GluR2 subunit, which normally renders AMPA receptors calcium impermeable, is thought to play a pivotal role for postictal neuronal death (GluR2 hypothesis). Using a specific GluR2 antiserum, postictal hippocampal GluR2 protein expression was investigated and compared to GluR1 between 6 and 96 h after seizure induction. In addition, postictal protein expression of a recently cloned AMPA receptor binding protein (ABP), which anchors AMPA receptors in the plasma membrane was also analyzed, to address the question of whether its protein expression is associated with neuronal death or survival. At 6 h after seizure induction, GluR2 immunoreactivity (IR) in CA3 was more markedly reduced compared to GluR1, but at 24 h GluR2 IR reattained control levels. More importantly, GluR2 IR was also markedly, but transiently decreased between 6 and 48 h in hippocampal CA1 neurons, but no significant cell loss was observed. These findings modify the GluR2 hypothesis in so far as only a subset of, but not all, hippocampal CA1 and CA3 pyramidal neurons may die due to reduced GluR2 levels with consecutive calcium overload through calcium-permeable AMPA receptors. ABP was induced postictally in presumed CA2 and a subpopulation of CA3 neurons and seems not to be involved in mechanisms of delayed neuronal death.

Expression of synaptopodin, an actin-associated protein, in the rat hippocampus after limbic epilepsy.

Synaptopodin, a 100 kD protein, associated with the actin cytoskeleton of the postsynaptic density and dendritic spines, is thought to play a role in modulating actin-based shape and motility of dendritic spines during formation or elimination of synaptic contacts. Temporal lobe epilepsy in humans and in rats shows neuronal damage, aberrant sprouting of hippocampal mossy fibers and subsequent synaptic remodeling processes. Using kainic acid (KA) induced epilepsy in rats, the postictal hippocampal expression of synaptopodin was analyzed by in situ hybridization (ISH) and immunohistochemistry. Sprouting of mossy fibers was visualized by a modified Timm's staining. ISH showed elevated levels of Synaptopodin mRNA in perikarya of CA3 principal neurons, dentate granule cells and in surviving hilar neurons these levels persisted up to 8 weeks after seizure induction. Synaptopodin immunoreactivity in the dendritic layers of CA3, in the hilus and in the inner molecular layer of the dentate gyrus (DG) was initially reduced. Eight weeks after KA treatment Synaptopodin protein expression returned to control levels in dendritic layers of CA3 and in the entire molecular layer of the DG. The recovery of protein expression was accompanied by simultaneous supra- and infragranular mossy fiber sprouting. Postictal upregulation of Synaptopodin mRNA levels in target cell populations of limbic epilepsy-elicited damage and subsequent Synaptopodin protein expression largely co-localized with remodeling processes as demonstrated by mossy fiber sprouting. It may thus represent a novel postsynaptic molecular correlate of hippocampal neuroplasticity.

CT and MRI findings in gliomatosis cerebri: a neuroradiologic and neuropathologic review of diffuse infiltrating brain neoplasms.

The aim of the study was to develop objective criteria that might be helpful for the diagnosis of gliomatosis cerebri (GC) with the highest possible probability based on both the neuroradiological and histopathological findings. Imaging findings in 14 patients with diffuse infiltrating brain neoplasms were studied by two neuroradiologists. Computed tomography and MRI scans were compared with each other side by side. The extent and kind of disease were graded on a scale of 1-5. Interexamination agreement between the two methods was calculated using a kappa analysis. Neither of the neuroradiologists performed the examinations and both were blinded to the histopathological findings, which were also available for all patients, based on biopsy as well as follow-up CT and MRI studies. A neuroradiological-neuropathological correlation was performed. A score system helped to differentiate the findings in three categories: 1 = suggestive of GC; 2 = GC cannot be excluded; and 3 = others. Both CT and MRI were performed in 14 patients with clinical signs and symptoms of an intracerebral tumor. All examinations had diagnostic quality and showed the involvement of at least two brain lobes. Stereotactic biopsy was carried out in all patients. In 2 patients the neuropathological diagnosis was suggestive of GC, in 1 patient glioblastoma, in 2 patients astrocytoma, and in 5 patients nonspecific astrogliotic proliferation. In the remaining 4 cases anaplastic tumor infiltration was diagnosed. The neuroradiological findings in 5 cases were suggestive of GC; in 6 cases a GC could not excluded; and in 3 patients only a slight probability of GC was found. In 2 cases was the neuropathological and the neuroradiological diagnosis of GC concordant. Magnetic resonance imaging is significantly more sensitive than CT in the diagnosis of GC. However, even with multiple, MRI-guided stereotactic biopsies in correlation with intraoperative analysis of the sample by smear preparations by a neuropathologist the antemortem diagnosis of GC is still difficult. Discussion of neuropathological and neuroradiological findings in each case in combination with a score system may help to resolve discrepancies.

Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebral ischemia.

BACKGROUND AND PURPOSE: Pretreatment with intraventricular brain-derived neurotrophic factor (BDNF) reduces ischemic damage after focal cerebral ischemia. In this experiment we studied the effect of intravenous BDNF delivered after focal cerebral ischemia on neurological outcome, infarct size, and expression of proapoptotic and antiapoptotic proteins Bax and Bcl-2, respectively. METHODS: With the use of the suture occlusion technique, the right middle cerebral artery in rats was temporarily occluded for 2 hours. Thirty minutes after vessel occlusion, BDNF (300 microg/kg per hour in vehicle; n=12) or vehicle alone (n=13) was continuously infused intravenously for 3 hours. After 24 hours the animals were weighed and neurologically assessed on a 5-point scale. The animals were then killed, and brains underwent either 2,3,5-triphenyltetrazolium chloride staining for assessment of infarct volume or paraffin embedding for morphology and immunohistochemistry (Bax, Bcl-2). RESULTS: Physiological parameters (mean arterial blood pressure, PO(2), PCO(2), pH, body temperature, glucose) and weight revealed no difference between groups. Neurological deficit was improved in BDNF-treated animals versus controls (P:<0.05, unpaired, 2-tailed t test). Mean+/-SD infarct volume was 229.7+/-97.7 mm(3) in controls and 121.3+/-80.2 mm(3) in BDNF-treated animals (P:<0.05, unpaired, 2-tailed t test). Cortical infarct volume was 155.5+/-78.5 mm(3) in the placebo group and 69.9+/-50.2 mm(3) in the BDNF-treated group (P:<0.05, unpaired, 2-tailed t test). Subcortical infarct volume was 74.1+/-30.6 mm(3) in the placebo group and 51.1+/-26.8 mm(3) in the BDNF-treated group (P:=NS). Bax-positive neurons were significantly reduced in the ischemic penumbra in BDNF-treated animals (P:<0.05, unpaired, 2-tailed t test), whereas Bcl-2-positive neurons were significantly increased in this area (P:<0.001, unpaired, 2-tailed t test). CONCLUSIONS: This study demonstrates a neuroprotective effect of BDNF when delivered intravenously after onset of focal cerebral ischemia. As shown here, one possible mechanism of action of neuroprotection of BDNF after focal ischemia appears to be counterregulation of Bax/Bcl-2 proteins within the ischemic penumbra.

Metabotropic glutamate receptor subtypes are differentially expressed after transient cerebral ischemia without, during and after tolerance induction in the gerbil hippocampus.

Postischemic delayed neuronal death (DND) of hippocampal CA1 neurons can be prevented by a preconditioning sublethal ischemic stimulus. To check for possible participation of metabotropic glutamate receptors (mGluRs) in neuronal death or survival, we analyzed postischemic protein expression of subtypes 1b and 5 of group I mGluRs, which are thought to exert neurotoxic effects after pathological activation due to ischemia, and subtypes 2 and 3 of group II mGluRs, which in contrast are thought to be neuroprotective in this state, respectively. Therefore, three groups of gerbils with reperfusion intervals between 8 h and 4 days (n=5 each) were investigated: one group was subjected to 5 min ischemia, resulting in DND of CA1 neurons, a second group to a tolerance inducing 2.5 min period of ischemia and a third group to 5 min ischemia after prior tolerance induction. The major finding was a transient postischemic reduction of mGluR1b and 5 expression in the ischemic tolerant CA1 subfield at 8 h. This downregulation of neurotoxic mGluRs may indicate a contribution to the survival of highly vulnerable CA1 neurons in the ischemic tolerant state.

Temporary changes of the AP-1 transcription factor binding activity in the gerbil hippocampus after transient global ischemia, and ischemic tolerance induction.

Global forebrain ischemia of 5-min duration results in delayed neuronal death (DND) of CA1 neurons in the gerbil hippocampus. DND can be prevented by a preconditioning sublethal ischemic stimulus (2. 5 min), a phenomenon, known as ischemic tolerance induction. Striking evidence exists for the involvement of regulatory transcription factors encoded by immediate early genes (IEGs) in the fate of CA1 neurons. Here, we investigated by electrophoretic mobility shift assay (EMSA) the postischemic changes of the DNA binding activity of the Activator Protein-1 (AP-1) transcription factor complex after preconditioning, lethal ischemia, and after acquisition of an ischemic tolerant state. A short duration peak of AP-1 binding activity at 3 h of reperfusion was a hallmark of ischemic tolerance induction. The kinetics of this activation profile, i.e. the rapid linear increase between 1 and 3 h and a similar rapid decline at 6 or 12 h of reperfusion are prominent within the CA1 and CA3 region of all ischemic groups which are designated for neuronal survival. No changes in the c-Jun and ATF-2 immunoreactivity were observed in the CA1 region, however an increase in only c-Jun immunoreactivity occurred in concordance with the elevation of AP-1 binding in the CA3 region. The results clearly demonstrate a differential regulation of AP-1 binding activity in CA1 during and after acquisition of an ischemic tolerant state in contrast to ischemia leading to neuronal death. The early peak at 3 h of reperfusion in AP-1 binding affinity observed in the single 2.5 min and the ischemic tolerant groups suggests a protective role of early AP-1 activation, whereas failure of this initial activation may contribute to DND. Our data furthermore suggest, that elevation of the AP-1 binding activity in the CA1 and CA3 regions underlies a different regulatory mechanism in the gerbil hippocampus after ischemic stress.

Long-term TGFâ2 protein expression in heterotopic cortical grafts located in the rat striatum.

PURPOSE: Transforming growth factor beta 2 (TGFâ2) is a multifunctional cytokine thought to play a crucial role in neuronal growth, differ-entiation and survival. In the cortex of adult rats, TGFâ2 is constitutively expressed in a subset of neurons and astrocytes. In the present study we analyzed whether TGFâ2 is also present in intrastriatal transplants of cortical anlage. In addition we investigated the temporo-spatial expression pattern of TGF2 in âthe surrounding host striatum. METHODS: Cortical primordia of rat fetuses (E14) were stereotactically grafted into the rostral striatum of adult recipient rats. Grafts were allowed to differentiate for 1, 2, 3, 4, 8 weeks or one year, respectively, followed by morphological and immunohistochemical analysis. RESULTS: From week 2 on, TGFâ 2-immunoreactivity (IR) was detectable in transplanted neurons. Within the graft, GFAP-IR was already present one week after transplantation, whereas TGFâ2-immunostained astrocytes were first seen after 2 weeks. One year after transplanta-tion, TGFâ2 positive neurons and astrocytes were still present. In the host striatum and at the graft-host interface an increase of TGFâ2-immu-noreactive astrocytes first occured after one week both in grafted animals and in sham-operated (lesioning without grafting) rats. CONCLUSIONS: Our data suggest that at least a subpopulation of transplanted neurons develops a phenotype as cortical neurons in situ with respect to TGFâ2 expression. Upregulation of astrocytic TGFâ2 expression within the graft, however, is due to the trauma imposed by the transplantation procedure rather than an intrinsic differentiation program of co-grafted astrocytes.

Telepathology in neurosurgery.

In most tumor cases of neurosurgery, we need to have a rapid section diagnostic of the tumor during the course of surgery. When we have received the results that diagnose the exact dignity of the tumor, we devise the operation strategy for the continuing course of surgery. The tissue sample is sent by taxi to the pathological institute in Heidelberg. It takes approximately 45-60 min until we receive the results by telephone. Many centers are far away from a pathological institute and the patient may need to be re-operated on there. In stereotaxy it is still more important. We need approximately 15-25 specimens during a stereotaxy, so we can be sure we have a sample with some of the tumor tissue present. With direct contact to a pathological institute we could reduce this dramatically. We prepared a methylen blue slide and used a histological microscope with a video camera attached to it and a digitizer interface for digitized pictures. By use of a modem we send the pictures by telephone line to the pathological institute, where they are assessed. We currently have direct contact with a pathologist so they can tell us from which part of the tumor we should send the other histological pictures. The procedure takes about twenty minutes. By using this procedure the distance to the pathological institute is irrelevant. The system costs approximately $10,000, covering the cost mostly of the microscope and the camera (but we already had the microscope) and can be built by anybody with minimal requirements.

Temporo-spatial expression of bFGF and TGFbeta2 in embryonic dopaminergic grafts in a rat model of Parkinson's disease.

In the present study we analyzed the temporo-spatial expression pattern of basic fibroblast growth factor (bFGF) and transforming growth factor beta 2 (TGFbeta2) in embryonic dopaminergic transplants in the 6-hydroxydopamine rat model of Parkinson's disease. The grafts differentiated for 1, 2, 4 and 8 weeks, respectively and were then analyzed using antibodies directed against tyrosine hydroxylase, bFGF and TGFbeta2. At all time points investigated, grafts contained tyrosine hydroxylase immunoreactive neurons. One week after transplantation the grafts displayed no immunoreactivity for bFGF and TGFbeta2. In more mature grafts (starting at 2 weeks post transplantation) bFGF and TGFbeta2 immunoreactivity became detectable within the graft and at the graft-host interface but was restricted only to astrocytes. In the striatum surrounding the graft, a transient increase of TGFbeta2 immunoreactive astrocytic processes was observed between 1 and 2 weeks after transplantation. This temporo-spatial expression pattern of TGFbeta2 immunoreactive astrocytes suggests that the upregulation of TGFbeta2 is more likely due to the trauma imposed by the transplantation procedure than to an intrinsic differentiation program. Lack of both bFGF and TGFbeta2 expression in grafted dopaminergic neurons compared to their normal expression in the adult rat substantia nigra indicates that these transplanted neurons do not develop their complete physiological phenotype. Together with the observed deficiency in astrocytic bFGF early after grafting this may be responsible for the poor survival of grafted embryonic dopaminergic cells.

Epstein-Barr virus meningoencephalitis with a lymphoma-like response in an immunocompetent host.

We report the clinical and neuropathological findings in an immunocompetent 19-year-old patient with a fatal acute Epstein-Barr virus (EBV) meningoencephalitis and a lymphoma-like B-lymphocyte response. Our results suggest that an immunotoxic rather than direct viral neuronal invasion mediates brain damage in EBV encephalitis and rule out primary central nervous system lymphoma (PCNSL) in our patient. We discuss immunosuppression as a therapeutic option, because present strategies mainly consist of symptomatic therapy due to unclear pathogenesis and nonavailability of effective antiviral agents.

Multivariate logistic analysis of dose-effect relationship and latency of radiomyelopathy after hyperfractionated and conventionally fractionated radiotherapy in animal experiments.

PURPOSE: We examined in rats whether the radiation tolerance of spinal cord is enhanced by using hyperfractionated radiotherapy compared to a conventional schedule. Higher tolerable doses to the spinal cord would allow dose escalation to the tumor and thus possibly lead to higher cure rates, especially in tumors with high cell proliferation. METHODS AND MATERIALS: Cervical spinal cord of 276 healthy rats was irradiated over 6 weeks hyperfractionally with single doses ranging from 0.75-2.5 Gy up to total doses ranging from 45-150 Gy (60 fractions) and conventionally with single doses of 1.5-4.0 Gy up to total doses of 45-120 Gy (30 fractions). The rats were examined neurologically and sacrificed when paralysis of the hind legs occurred. After fixation, spinal cord was removed and examined histologically. Dose-effect relationship and latency from the beginning of radiotherapy to the onset of paralysis were computed and analyzed using a multivariate logistic regression model. RESULTS: The model fitted the observed data excellently. There were highly significant effects both for the dose level and for the treatment regimen. Latency analysis showed earlier and more intense acute side effects after hyperfractionation but radiomyelopathy occurred markedly later. CONCLUSIONS: The sparing effect of hyperfractionation on spinal cord as predicted by radiobiologists could be confirmed in our experiments. Thus, it seems possible to escalate tumor doses using hyperfractionation without enhanced risk to spinal cord but with higher probability of tumor cure.