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M Kiessling

Publications and source records attributed to M Kiessling.

At least 19 recordsLinked to original sources
PubMed2004

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.

Animals↗
PubMed2001

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.

Adolescent↗
PubMed2001

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.

Animals↗
PubMed2001

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.

Abnormalities, Multiple↗
PubMed2001

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.

Animals↗
PubMed2000

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.

Animals↗
PubMed2000

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.

Animals↗
PubMed2000

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.

Animals↗
PubMed1999

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.

Age Factors↗
PubMed1999

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.

Adolescent↗
PubMed1999

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.

Brain Diseases↗
PubMed1998

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.

Animals↗
PubMed1998

BDNF and TrkB expression in intrastriatal ventral mesencephalic grafts in a rat model of Parkinson's disease.

We investigated the expression of BDNF and its high affinity receptor trkB in fetal dopaminergic grafts in a rat model of Parkinson's disease. Grafts were allowed to differentiate for 7, 14, 28, or 56 days, respectively and were analyzed immunocytochemically thereafter with antibodies directed against tyrosine hydroxylase, BDNF and trkB. At all time points investigated, grafts contained tyrosine hydroxylase immunoreactive neurons. Immature grafts (7 days) displayed no immunoreactivity for BDNF which was restricted to glial cells at the graft-host interface. After longer differentiation periods BDNF-immunoreactivity was detectable in neurons and astrocytes within the grafts. No trkB immunoreactivity was found in immature grafts but a strong signal for trkB emerged in grafted neurons older than 14 days whereas glial cells remained unlabeled at all time points investigated. Expression of BDNF and trkB in grafted neurons and of BDNF in surrounding glial cells suggests an autocrine or paracrine action of BDNF on dopaminergic neurons possibly mediated by activated glia.

Animals↗
PubMed1997

Expression of cerebellar specific glutamate and GABAA receptor subunits in heterotopic cerebellar grafts.

In the cerebellum, up- and downregulation of specific GABAA and NMDA receptor subunits coincide with granule cell migration and differentiation. In this study, in situ hybridization techniques with GABAA and NMDA receptor subunit specific probes were employed to assess whether the molecular phenotype of heterotopically grafted cerebellar granule cells corresponds to that of normal cerebellum. The cerebellar anlage of rat fetuses was stereotactically grafted into the rostral striatum of adult rats. Eight weeks after transplantation, analysis demonstrated acquisition of an adult differentiation status reflected by abundant GABAA alpha 6 and NR2C mRNA expression in granule cells. Complete lack of NR2B transcripts, molecular markers of immature granule cells, argues against persistence of undifferentiated cells. The data suggest that intrinsic cell-autonomous factors largely determine the molecular commitment of granule cells and that a restricted specific environment is not necessary to promote granule cell differentiation.

Animals↗
PubMed1997

Growth inhibition by dominant-negative mutations of the neu-encoded oncoprotein.

In the present study, kinase-deficient mutants of the neu gene were constructed in order to generate dominant-negative receptor molecules, which should abolish phosphorylation of receptor complexes. One construct carried a mutation of the putative ATP-binding site (K758M), while the other mutant was generated by deletion of the kinase domain (ID400). Neither receptor showed phosphorylation by in vitro kinase assay. When NIH3T3 fibroblasts were co-transfected by the oncogenic neu gene and one of either construct, the transforming effect could be partially reversed. Therefore, kinase-negative mutations of the neu-encoded receptor seemed to have a dominant-negative effect on the action of the activated protein. To test this hypothesis, rat neurinoma cell lines containing oncogenic neu genes were transfected with the constructs. Expression of the kinase-defective mutants and reduced phosphorylation could be detected in different clones derived from single transfected cells. Striking growth inhibition and reduction of colony formation in soft agar were observed in these cell lines when compared with untransfected cells. Thus, kinase-deficient mutants exert a dominant-negative effect on phosphorylation of receptor complexes, resulting in a reversion of the transformed phenotype.

3T3 Cells↗
PubMed1997

Effect of global system for mobile communication (GSM) microwave exposure on blood-brain barrier permeability in rat.

We investigated the effects of global system for mobile communication (GSM) microwave exposure on the permeability of the blood-brain barrier using a calibrated microwave exposure system in the 900 MHz band. Rats were restrained in a carousel of circularly arranged plastic tubes and sham-exposed or microwave irradiated for a duration of 4 h at specific brain absorption rates (SAR) ranging from 0.3 to 7.5 W/kg. The extravasation of proteins was assessed either at the end of exposure or 7 days later in three to five coronal brain slices by immunohistochemical staining of serum albumin. As a positive control two rats were subjected to cold injury. In the brains of freely moving control rats (n = 20) only one spot of extravasated serum albumin could be detected in one animal. In the sham-exposed control group (n = 20) three animals exhibited a total of 4 extravasations. In animals irradiated for 4 h at SAR of 0.3, 1.5 and 7.5 W/kg (n = 20 in each group) five out of the ten animals of each group killed at the end of the exposure showed 7, 6 and 14 extravasations, respectively. In the ten animals of each group killed 7 days after exposure, the total number of extravasations was 2, 0 and 1, respectively. The increase in serum albumin extravasations after microwave exposure reached significance only in the group exposed to the highest SAR of 7.5 W/kg but not at the lower intensities. Histological injury was not observed in any of the examined brains. Compared to other pathological conditions with increased blood-brain barrier permeability such as cold injury, the here observed serum albumin extravasations are very modest and, moreover, reversible. Microwave exposure in the frequency and intensity range of mobile telephony is unlikely to produce pathologically significant changes of the blood-brain barrier permeability.

Animals↗
PubMed1997

Induction of FOS and JUN proteins during focal epilepsy: congruences with and differences to [14C]deoxyglucose metabolism.

fos and jun belong to multigene families coding for transcription factors. These cellular immediate-early genes (IEGs) are thought to be involved in coupling neuronal excitation to changes of target gene expression. Immunocytochemistry with specific antisera was used to assess regional levels of five IEG-encoded proteins (c-FOS, FOS B, c-JUN, JUN B and JUN D) in a rat model of penicillin-induced focal epilepsy. To assess whether brain regions with post-ictal de novo transcription factor synthesis correspond to those areas with increased glucose metabolism, IEG expression patterns were compared with [14C]deoxyglucose autoradiography performed in a subset of animals. The results demonstrated marked induction of c-FOS, FOS B, c-JUN and JUN B but not JUN D in the cortical epileptic focus. Thereby, individual IEG-encoded proteins exhibited differential temporal and spatial expression patterns. Within the epileptic focus, IEG expression correlated with increased glucose metabolism. In contrast, IEG induction was not observed in brain areas distant from the epileptic focus that also demonstrated increased glucose metabolism, such as homotopic contralateral motor cortex and ipsilateral thalamic nuclei. These findings indicate that in focal epilepsy changes of the genetic programme are restricted to neurons of the epileptic focus. In contrast, the increased [14C]deoxyglucose metabolism in contralateral motor cortex and ipsilateral thalamus seems to indicate functional changes.

Animals↗