Biomedical subjects

Ulrich Bogdahn

Publications and source records attributed to Ulrich Bogdahn.

At least 19 recordsLinked to original sources

PubMed2006

Toll-like receptor triggered dendritic cell maturation and IL-12 secretion are necessary to overcome T-cell inhibition by glioma-associated TGF-beta2.

Malignant gliomas are able to secrete large amounts of immunosuppressive cytokines like transforming growth factor beta 2 (TGF-beta2) and regularly escape from immune surveillance. Many strategies have been developed to induce potent anti-glioma responses, among those the use of dendritic cells (DC) as therapeutic vaccines. Here, we report that both mature DC and IL-12 secretion are necessary to overcome T-cell inhibition by TGF-beta2. Flow cytometric analyses showed that TGF-beta2 does not suppress the upregulation of MHC (major histocompatibility complex) class II molecules and the T cell stimulatory capacity of human DC that were stimulated with a strong cytokine cocktail containing tumor necrosis factor alpha (TNF-alpha), IL-1beta, IL-6 and prostaglandin E2 (PGE2). Moreover, TGF-beta2 signaling studies revealed that these cytokine-matured DC become unresponsive to TGF-beta2. Although both mature and immature DC expressed comparable amounts of the TGF-beta receptor type II, Smad2 phosphorylation and subsequent upregulation of Smad7 was inhibited in mature DC, but not immature DC. However, further analysis revealed that mature DC alone are not sufficient to mediate full T cell activation in the presence of TGF-beta2, unless IL-12 is added to the DC/T-cell coculture. Finally, we demonstrate that MHC class II expression and IL-12 secretion by DC are not disturbed by TGF-beta2 after DC stimulation with a modified maturation cocktail containing the Toll-like receptor (TLR)-ligands Poly I:C or R848, TNF-alpha, IL-1beta and INF-gamma. These data imply that mature DC retaining their capacity to produce IL-12 are of favorable use in glioma immunotherapy and suggest that TLR triggering of DC plays an important role to elicit a strong immune response in the immunosuppressive environment of malignant gliomas.

Blotting, Western↗

PubMed2006

Fischer-344 rats are unsuitable for the MCAO filament model due to their cerebrovascular anatomy.

Middle cerebral artery occlusion (MCAO) in Fischer-344 rats results in a small variance of infarct size. However, complications are frequent especially in aged Fisher-344 rats undergoing endovascular suture occlusion of the middle cerebral artery. Analyzing our experiences with 165 Wistar, 13 Sprague-Dawley and 10 F-344 rats, we compared the incidence of impossible thread advancement and subarachnoid hemorrhage, respectively. Magnetic resonance angiography (MRA) was applied to study the course of the internal carotid artery (ICA) in Fischer and Wistar rats. Finally, we performed a structured review of the literature from 1991 to 2005 evaluating reports on Fischer rats subjected to intraluminal filament MCAO. Complications like fruitless filament advancement or subarachnoid hemorrhage were found to be significantly more frequent in Fischer rats than in other strains. MRA revealed significantly more pronounced kinking of the ICA in F-344 than in Wistar rats. In seven publications available on filament MCAO in F-344 rats, complication rates of 50-100% were reported, corroborating our data. Surgical difficulties accompanied by high complication rates due to their cerebrovascular anatomy make Fischer rats unsuitable for filament MCAO. If the use of Fischer rats for studies on focal cerebral ischemia is indicated, other ischemia models than intraluminal suture occlusion should be chosen.

Aging↗

PubMed2006

Failure of Schwann cells as supporting cells for adult neural progenitor cell grafts in the acutely injured spinal cord.

Adult neural progenitor cells (NPC) co-grafted with fibroblasts replace cystic lesion defects and promote cell-contact-mediated axonal regeneration in the acutely injured spinal cord. Fibroblasts are required as a platform to maintain NPC within the lesion; however, they are suspected to create an inhospitable milieu for regenerating central nervous system (CNS) axons. Therefore, we thought to replace fibroblasts by primary Schwann cells, which might serve as a superior scaffold to maintain NPC within the lesion and might further enhance axon regrowth and remyelination following spinal cord injury. Adult rats underwent a cervical dorsal column transection immediately followed by transplantation of either NPC/Schwann cell or NPC/Schwann cell/fibroblast co-grafts. Animals receiving Schwann cell or fibroblast grafts alone, or Schwann cell/fibroblast co-grafts served as controls. At 3 weeks after injury/transplantation, histological analysis revealed that only fibroblast-containing grafts were able to replace the cystic lesion defect. In both co-cultures and co-grafts, Schwann cells and NPC were segregated. Almost all NPC migrated out of the graft into the adjacent host spinal cord. As a consequence, only peripheral-type myelin, but no CNS-type myelin, was detected within co-grafts containing NPC/Schwann cells. Corticospinal axon regeneration into Schwann-cell-containing co-grafts was reduced. Taken together, Schwann cells within NPC grafts contribute to remyelination. However, Schwann cells fail as a supporting platform to maintain NPC within the graft and impair CNS axon regeneration; this makes them an unfavorable candidate to support/augment NPC grafts following spinal cord injury.

Animals↗

PubMed2006

Mesenchymal stem cells instruct oligodendrogenic fate decision on adult neural stem cells.

Adult stem cells reside in different tissues and organs of the adult organism. Among these cells are MSCs that are located in the adult bone marrow and NSCs that exist in the adult central nervous system (CNS). In transplantation experiments, MSCs demonstrated neuroprotective and neuroregenerative effects that were associated with functional improvements. The underlying mechanisms are largely unidentified. Here, we reveal that the interactions between adult MSCs and NSCs, mediated by soluble factors, induce oligodendrogenic fate decision in NSCs at the expense of astrogenesis. This was demonstrated (a) by an increase in the percentage of cells expressing the oligodendrocyte markers GalC and myelin basic protein, (b) by a reduction in the percentage of glial fibrillary acidic protein (GFAP)-expressing cells, and (c) by the expression pattern of cell fate determinants specific for oligodendrogenic differentiation. Thus, it involved enhanced expression of the oligodendrogenic transcription factors Olig1, Olig2, and Nkx2.2 and diminished expression of Id2, an inhibitor of oligodendrogenic differentiation. Results of (a) 5-bromo-2'-deoxyuridine pulse-labeling of cells, (b) cell fate analysis, and (c) cell death/survival analysis suggested an inductive mechanism and excluded a selection process. A candidate factor screen excluded a number of growth factors, cytokines, and neurotrophins that have previously been shown to influence neurogenesis and neural differentiation from the oligodendrogenic activity derived from the MSCs. This work might have major implications for the development of future transplantation strategies for the treatment of degenerative diseases in the CNS.

Cell Differentiation↗

PubMed2006

The promotion of oriented axonal regrowth in the injured spinal cord by alginate-based anisotropic capillary hydrogels.

Appropriate target reinnervation and functional recovery after spinal cord injury depend on longitudinally directed regrowth of transected axons. To assess the capacity to promote directed axon regeneration, alginate-based highly anisotropic capillary hydrogels (ACH) were introduced into an axon outgrowth assay in vitro and adult rat spinal cord lesions in vivo. In an entorhino-hippocampal slice culture model, alginate-based scaffolds elicit highly oriented linear axon regrowth and appropriate target neuron reinnervation. Coating of alginate-based ACH with the extracellular matrix components collagen, fibronectin, poly L-ornithine and laminin did not alter the axon regrowth response as compared to uncoated alginate-based ACH. After implantation into acute cervical spinal cord lesions in adult rats, alginate-based ACH integrate into the spinal cord parenchyma without major inflammatory responses, maintain their anisotropic structure and in parallel to findings in vitro induce directed axon regeneration across the artificial scaffold. Furthermore, adult neural progenitor cells (NPC), which have been shown to promote cell-contact-mediated axon regeneration, can be seeded into alginate-based ACH as a prerequisite to further improve the regenerative capacity of these artificial growth supportive matrices. Thus, alginate-based ACH represent a promising strategy to induce directed nerve regrowth following spinal cord injury.

Alginates↗

PubMed2006

Effects of the implementation of a telemedical stroke network: the Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria, Germany.

BACKGROUND: Telemedical networks are a new approach to improve stroke care in community settings. We aimed to assess the effects of a stroke network with telemedical support in Germany on quality of care, according to acute processes and long-term outcome. METHODS: Five community hospitals without pre-existing specialised stroke care were included in a network with telemedical support by two academic hospitals. In a non-randomised, open intervention study, five community hospitals without specialised stroke care served as the control group, matched individually to the network hospitals by predefined characteristics. Stroke patients admitted consecutively to one of the participating hospitals between July 7, 2003, and March 31, 2005, were included in the study. Patients in network and control hospitals were assessed in the same manner and were followed up for vital status, living situation, and disability at 3 months. Poor outcome was defined by death, institutional care, or disability (Barthel index <60 or modified Rankin scale >3). Predefined indicators for quality of acute stroke care were achieved. FINDINGS: A total of 5696 patients with a sudden, non-convulsive loss of neurological function who were diagnosed with having suspected stroke were admitted to the ten hospitals participating in the study. After exclusion, 3122 were included in the final analysis, of whom 1971 (63%) were treated in the network hospitals. All indicators related to quality of acute stroke care were more commonly met in the network than in the control hospitals. After 3 months, 44% of patients treated in network hospitals versus 54% treated in control hospitals had a poor outcome (p<0.0001). In multivariate regression analysis, treatment in network hospitals independently reduced the probability of a poor outcome (odds ratio 0.62, 95% CI 0.52-0.74; p<0.0001). INTERPRETATION: Telemedical networks with academic stroke centres offer new and innovative approaches to improve acute stroke care at community level for stroke patients living in non-urban areas.

Academic Medical Centers↗

PubMed2006

Transforming growth factor-beta1 is a negative modulator of adult neurogenesis.

Transforming growth factor (TGF)-beta1 has multiple functions in the adult central nervous system (CNS). It modulates inflammatory responses in the CNS and controls proliferation of microglia and astrocytes. In the diseased brain, TGF-beta1 expression is upregulated and, depending on the cellular context, its activity can be beneficial or detrimental regarding regeneration. We focus on the role of TGF-beta1 in adult neural stem cell biology and neurogenesis. In adult neural stem and progenitor cell cultures and after intracerebroventricular infusion, TGF-beta1 induced a long-lasting inhibition of neural stem and progenitor cell proliferation and a reduction in neurogenesis. In vitro, although TGF-beta1 specifically arrested neural stem and progenitor cells in the G0/1 phase of the cell cycle, it did not affect the self-renewal capacity and the differentiation fate of these cells. Also, in vivo, TGF-beta1 did not influence the differentiation fate of newly generated cells as shown by bromo-deoxyuridine incorporation experiments. Based on these data, we suggest that TGF-beta1 is an important signaling molecule involved in the control of neural stem and progenitor cell proliferation in the CNS. This might have potential implications for neurogenesis in a variety of TGF-beta1-associated CNS diseases and pathologic conditions.

Animals↗

PubMed2006

Targeted transgene expression in neuronal precursors: watching young neurons in the old brain.

Progress in the field of neurogenesis is limited by the lack of animal models allowing direct detection and analysis of living cells participating in neurogenesis. We engineered a transgenic mouse model that expresses the fluorescent reporter proteins enhanced green fluorescent protein or Discoma sp. reef coral red fluorescent protein under the control of the doublecortin (DCX) promoter, a gene specifically and transiently active in neuronal precursors and young neurons. The expression of the reporter proteins correlated with expression of the endogenous DCX protein, and with developmental and adult neurogenesis. Neurogenesis was unaffected by the presence of the fluorescent proteins. The transgenic mice allowed direct identification of the very few newly generated neurons present in the aged brain. We performed electrophysiological analysis and established that newly generated hippocampal granule cells in aged and young mice shared identical physiological properties. Hence, although the rate of neurogenesis tapers with ageing, a population of highly excitable young neurons indistinguishable to those found in younger animals is continuously generated. Therefore, maintenance of the fundamental properties of neuronal precursors even at advanced age suggests that stimulation of neurogenesis may constitute a valid strategy to counteract age-related neuronal loss and cognitive declines.

Age Factors↗

PubMed2006

Effective silencing of EGFR with RNAi demonstrates non-EGFR dependent proliferation of glioma cells.

The epidermal growth factor receptor (EGFR, ErbB1) is frequently dysregulated in a variety of solid human tumors, including malignant glioma. EGFR expression has been associated with disease progression, resistance to standard therapies and poor survival. The application of small interfering RNAs (siRNAs) has become an effective and highly specific tool to modulate gene expression, and a wide range of oncogenes have been silenced successfully. Here we show the siRNA-mediated down-regulation of EGFR in two established glioma cell lines with different EGFR expression levels (U373 MG, LN18). The expression of EGFR mRNA and protein was down-regulated by 70-90%. However, siRNA treatment had no inhibitory effect on cell proliferation, migration and activation status of EGFR-coupled signaling cascades. In accordance with these results, gene expression analysis with microarrays revealed only small, albeit specific changes in expression patterns. In conclusion, these data indicate that the specific down-regulation of EGFR might not be sufficient for a single agent therapeutic approach in malignant glioma.

Brain Neoplasms↗

PubMed2005

Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009.

TGF-beta overexpression is a hallmark of various malignant tumors. This is due to the pivotal role of TGF-beta as it regulates key mechanisms of tumor development, namely immunosuppression, metastasis, angiogenesis, and proliferation. We have developed a new immunotherapeutic approach for the treatment of malignant tumors based on the specific inhibition of TGF-beta2 by the antisense oligodeoxynucleotide AP 12009. After providing preclinical proof of concept, we assessed safety and efficacy of AP 12009 in clinical phase I/II open-label dose escalation studies in high-grade glioma patients. Median survival time after recurrence exceeded the up to date literature data for chemotherapy. A phase I/II study in pancreatic carcinoma and malignant melanoma is currently ongoing. Our results implicate targeted TGF-beta2 suppression as a promising therapeutic approach for malignant tumor therapy.

Animals↗

PubMed2005

Tenascin-C protein is induced by transforming growth factor-beta1 but does not correlate with time to tumor progression in high-grade gliomas.

BACKGROUND: Tenascin-C is an extracellular matrix protein known to correlate with prognosis in patients with glioblastoma, probably by stimulation of invasion and neoangiogenesis. Transforming Growth Factor-beta1 (TGF-beta1) plays an important role in the biology of high-grade gliomas, partly by regulating invasion of these tumors into parenchyma. This study was designed to evaluate if TGF-beta1 induces the expression and deposition of Tenascin-C in the extracellular matrix of high-grade gliomas which may be pivotal for the invasion of these tumors into healthy parenchyma. METHODS: A series of 20 high-grade gliomas was stained immunohistochemically with Tenascin-C- and TGF-beta1- specific antibodies. Expression levels of both proteins were evaluated and correlated with each other, time to progression and molecular and morphological markers of invasion. A quantitative PCR assay was performed evaluating the induction of Tenascin-C mRNA by treatment with TGF-beta1 in vitro. RESULTS: Tenascin-C was expressed in 18 of 19 (95%) evaluable tumors, whereas 14 of 20 tumors (70%) expressed TGF-beta1 in a significant percentage of cells. Treatment with TGF-beta1 did induce the expression of Tenascin-C at the mRNA and protein level in vitro. The expression of Tenascin-C and TGF-beta1 did neighter statistically correlate with each other nor with time to progression. CONCLUSION: In our series, Tenascin-C and TGF-beta1 were expressed in the vast majority of high-grade gliomas. We could not detect a correlation of one of the proteins with time to progression. Nevertheless, we describe induction of Tenascin-C by TGF-beta1, possibly providing a mechanism for the invasion of high-grade gliomas into healthy parenchyma.

Adult↗

PubMed2005

Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb.

Dopaminergic loss is known to be one of the major hallmarks of Parkinson disease (PD). In addition to its function as a neurotransmitter, dopamine plays significant roles in developmental and adult neurogenesis. Both dopaminergic deafferentation and stimulation modulate proliferation in the subventricular zone (SVZ)/olfactory bulb system as well as in the hippocampus. Here, we study the impact of 6-hydroxydopamine (6-OHDA) lesions to the medial forebrain bundle on proliferation and neuronal differentiation of newly generated cells in the SVZ/olfactory bulb axis in adult rats. Proliferation in the SVZ decreased significantly after dopaminergic deafferentation. However, the number of neural progenitor cells expressing the proneuronal cell fate determinant Pax-6 increased in the SVZ. Survival and quantitative cell fate analysis of newly generated cells revealed that 6-OHDA lesions induced opposite effects in the two different regions of neurogenesis in the olfactory bulb: a transient decrease in the granule cell layer contrasts to a sustained increase of newly generated neurons in the glomerular layer. These data point towards a shift in the ratio of newly generated interneurons in the olfactory bulb layers. Dopaminergic neurogenesis in the glomerular layer tripled after lesioning and consistent with this finding, the total number of tyrosine hydroxylase (TH)-positive cells increased. Thus, loss of dopaminergic input to the SVZ led to a distinct cell fate decision towards stimulation of dopaminergic neurogenesis in the olfactory bulb glomerular layer. This study supports the accumulating evidence that neurotransmitters play a crucial role in determining survival and differentiation of newly generated neurons.

Animals↗

PubMed2005

Predictors of survival after severe dysphagic stroke.

BACKGROUND AND PURPOSE: Dysphagia is estimated to occur in up to 50% of the stroke neurorehabilitation population. Those patients with severe neurogenic oropharyngeal dysphagia (NOD) may receive feeding gastrostomy tubes (FGT) if noninvasive therapies prove ineffective in eliminating aspiration or sustaining adequate nutritional intake. Our aim was to quantify the recovery of swallowing function, and to identify variables predictive of survival after dysphagic stroke requiring FGT placement. METHODS: We identified consecutive stroke patients with severe dysphagic stroke requiring FGT placement admitted to a rehabilitation hospital between May 1998 and October 2001. The medical records were reviewed, and demographic, clinical, videofluoroscopic (VSS) and neuroimaging information were abstracted. A follow-up telephone interview was performed to determine whether the FGT was still in use, had been removed,or if the patient had died. State death certificate records were reviewed to ascertain date of death for subjects who had expired by the time of follow-up. Univariate and multivariate analyses were performed. RESULTS: 11.6 % (77/664) of stroke patients admitted during the study period had severe dysphagic stroke with FGT insertion. Follow-up was available for 66 (85.7 %) of these individuals at a mean of two years after acute stroke. On follow-up 64% (42/66) of the patients were alive and 45 % had had the FGT removed and resumed oral diets. On univariate analysis patients who were alive at the time of follow-up had received FGT feeding for a shorter period of time (p < 0.0003), showed no signs of aspiration on the Clinical Assessment of Feeding & Swallowing (CAFS,p < 0.020) and on the Videofluoroscopic Swallowing Study (VSS, 0.001), had a better discharge FIM-Score (Functional Independence Measure) for eating (p < 0.0002) and cognitive function (p < 0.002) as well as better discharge FCM-Score (Functional Communication Measure) for swallowing (p < 0.0001). On multivariate analysis we developed a model consisting of FGT removal at discharge from the rehabilitation hospital (p < 0.011) and non-aspiration during VSS (p < 0.040) that was significantly associated with longer survival time during follow-up. CONCLUSIONS: Severe dysphagia requiring FGT is common in patients with stroke referred for neurorehabilitation. Patients who had a FGT in place at the time of discharge from the stroke rehabilitation unit or aspirated during VSS were substantially more likely to have died by the time of follow-up compared to those who had had the FGT removed and had no signs of aspiration on VSS. However functional outcome measurements (FIM, FCM) including the cognitive function (attention, concentration etc.) could play an important role for prediction of swallowing regeneration and survival in neurorehabilitation. These findings may have practical utility in guiding physicians and speech language pathologists when advising patients and families about prognosis in stroke survivors with severe dysphagia.

Aged↗

PubMed2005

Can telemedicine contribute to fulfill WHO Helsingborg Declaration of specialized stroke care?

BACKGROUND: Providing stroke unit treatment for all stroke patients is a cross-national goal as stated in the WHO Helsingborg Declaration. In order to achieve specialized stroke care for a large area, two stroke centers and 12 community hospitals established an integrative stroke network. This evaluation was performed to analyze achieved advances in stroke management. METHODS: Core network elements are: (1) establishing stroke wards in all hospitals; (2) continuous training in stroke treatment; (3) telemedicine service staffed by a 24 h/day 'strokologist' with capability for high-speed videoconferencing and transfer of CT/MRI images. Data were prospectively documented in the databank of the telestroke service, in the Bavarian Stroke Registry and in the controlling departments. RESULTS: In 2003, 4,179 stroke patients were admitted to the regional network hospitals. Between February 2003 and January 2004 a total of 2,182 teleconsultations were conducted. 250 teleconsultations yielded a nonvascular diagnosis. Indicators for stroke management quality improved compared with other hospitals without stroke unit: the frequency of CT/MRI within 3 h was 59% compared to 46%, frequency of speech therapy 36% (21%), and of occupational therapy 38% (12%). Eighty-six (2.1%) of the patients received systemic thrombolysis compared to 10 patients in the preceding year. Mean length of in-hospital stay decreased from 12.4 in 2002 to 9.7 days in 2003. CONCLUSIONS: This stroke network concept leads to a substantial improvement of stroke management. Telemedicine contributes to an early etiological assessment and fills the gap of specialized stroke expertise in neurologically underserved areas.

Acute Disease↗

PubMed2005

Transcranial ultrasound brain perfusion assessment with a contrast agent-specific imaging mode: results of a two-center trial.

BACKGROUND AND PURPOSE: The purpose of this study was to assess brain perfusion with an ultrasound contrast-specific imaging mode and to prove if the results are comparable between 2 centers using a standardized study protocol. METHODS: A total of 32 individuals without known cerebrovascular disease were included in the study. Perfusion studies were performed ipsilaterally in an axial diencephalic plane after intravenous administration of 0.75 mL of Optison. Offline time intensity curves (TIC) were generated in different anatomic regions. Both centers used identical study protocols, ultrasound machines, and contrast agent. RESULTS: In both centers, the comparison of the parameter time to peak intensity (TPI) revealed significantly shorter TPIs in the main vessel structures compared with any parenchymal region of interest (ROI), whereas no significant differences were seen between the parenchymal ROIs. The parameter peak intensity (PI) varied widely interindividually in both centers, whereas the inter-ROI comparison revealed statistical significance (P < 0.05) in most of the cases according to the following pattern: (1) lentiforme nucleus > thalamus and white matter region, (2) thalamus > white matter region, and (3) main vessel > any parenchymal structure. Similar results were achieved in both centers independently. CONCLUSIONS: The study demonstrates that brain perfusion assessment with an ultrasound contrast-specific imaging mode is comparable between different centers using the same study protocol.

Adult↗

PubMed2005

Long-term outcome after hemicraniectomy for space occupying right hemispheric MCA infarction.

OBJECTIVE: To examine the long-term prognosis in patients with 'malignant' supratentorial ischemia of the right hemisphere treated with hemicraniectomy, especially in respect to depression, with a focus on age as a possible predictor of outcome. METHODS: We performed a prospective, long-term, follow-up examination in 23 survivors of 32 patients (mortality 28.1%) treated with hemicraniectomy for malignant middle cerebral artery (MCA) infarction of the right hemisphere, who were identified in our data bank since 1993. Long-term was defined as at least 20 months after craniectomy. Outcome data consisted of the items functionality, depression and quality of life. Tests applied included the Barthel Index (BI), the modified Rankin Scale (mRS), Beck Depression Inventory (BDI) and stroke-specific quality of life (QoL) scale. RESULTS: Of the 23 patients 15 (65.2%) had a BI>or=60, 11 (47.8%) a mRS<4 and 9 (39.1%) a SS-QOL>or=60%, each representing a favourable outcome. In retrospect, 14 (60.9%) patients approved the surgery. Depression, i.e. a BDI>9, was diagnosed in 13 (56.5%) patients and 5 (38.5%) of them were treated with antidepressants. In a multiple linear regression analysis age at craniectomy was a predictor of a low BI (beta=-0.863; p=0.031), but not of the other outcome parameters. CONCLUSIONS: Depression is a common and rarely treated long-term complication after 'malignant' right hemispheric ischemia. While high age is a strong predictor of poor functional outcome, it has no impact on depression and retrospective approval of craniectomy.

Adult↗

PubMed2005

Thin corpus callosum and amyotrophy in spastic paraplegia--case report and review of literature.

We report the clinical, structural, functional and genetic characterization of a 37-year-old Caucasian female, presenting as a sporadic case of complicated spastic paraplegia with thin corpus callosum (CC), cognitive impairment, amyotrophy of the hand muscles and a sensorimotor neuropathy and review the literature for spastic paraplegia with thin CC. Magnetic resonance imaging (MRI) examination revealed a thin CC with fronto-parietal cortical atrophy. 18Fluordesoxyglucose positron emission tomography (FDG-PET) showed reduced cortical and thalamic metabolism. By transcranial magnetic stimulation, we delineated a severe impairment of transcallosal inhibition. Sequence analysis did not reveal disease causing mutations in the genes SLC12A6 (Andermann), Spastin (SPG 4), BSCL2 (SPG 17) and Spartin (SPG 20). We reviewed the literature for HSP with thin CC and found 113 HSP patients with thin CC previously described (35 with linkage to chromosome 15q13-15). Thin CC and peripheral neuropathy often appear together in spastic paraplegia and might be indicative for combined degeneration mechanism of central and peripheral axons.

Adult↗

PubMed2005

Adult retinal pigment epithelium cells express neural progenitor properties and the neuronal precursor protein doublecortin.

The adult mammalian retina is devoid of any detectable neurogenesis. However, different cell types have been suggested to potentially act as neural progenitors in the adult mammalian retina in vitro, such as ciliary body (CB), Muller glia, and retinal pigment epithelium (RPE) cells. In rodents and humans, strong evidence for neural stem or progenitor properties exists only for CB-derived cells, but not for other retinal cell types. Here, we provide a comparative analysis of adult rat CB- and RPE-derived cells suggesting that the two cell types share certain neural progenitor properties in vitro. CB and RPE cells expressed neural progenitor markers such as Nestin, Flk-1, Hes1, and Musashi. They proliferated under adherent and neurosphere conditions and showed limited self-renewal. Moreover, they differentiated into neuronal and glial cells based on the expression of differentiation markers such as the young neuronal marker beta-III tubulin and the glial and progenitor markers GFAP and NG2. Expression of beta-III tubulin was found in cells with neuronal and non-neuronal morphology. A subpopulation of RPE- and CB-derived progenitor cells expressed the neurogenesis-specific protein doublecortin (DCX). Interestingly, DCX expression defined a beta-III tubulin-positive CB and RPE fraction with a distinct neuronal morphology. In summary, the data suggest that RPE cells share with CB cells the potential to de-differentiate into a cell type with neural progenitor-like identity. In addition, DCX expression might define the neuronal-differentiating RPE- and CB-derived progenitor population.

Animals↗