Subthalamic nucleus but not entopeduncular nucleus deep brain stimulation enhances neurogenesis in the SVZ-olfactory bulb system of Parkinsonian rats.

Introduction: Deep brain stimulation (DBS) is a highly effective treatment option in Parkinson's disease. However, the underlying mechanisms of action, particularly effects on neuronal plasticity, remain enigmatic. Adult neurogenesis in the subventricular zone-olfactory bulb (SVZ-OB) axis and in the dentate gyrus (DG) has been linked to various non-motor symptoms in PD, e.g., memory deficits and olfactory dysfunction. Since DBS affects several of these non-motor symptoms, we analyzed the effects of DBS in the subthalamic nucleus (STN) and the entopeduncular nucleus (EPN) on neurogenesis in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats. Methods: In our study, we applied five weeks of continuous bilateral STN-DBS or EPN-DBS in 6-OHDA-lesioned rats with stable dopaminergic deficits compared to 6-OHDA-lesioned rats with corresponding sham stimulation. We injected two thymidine analogs to quantify newborn neurons early after DBS onset and three weeks later. Immunohistochemistry identified newborn cells co-labeled with NeuN, TH and GABA within the OB and DG. As a putative mechanism, we simulated the electric field distribution depending on the stimulation site to analyze direct electric effects on neural stem cell proliferation. Results: STN-DBS persistently increased the number of newborn dopaminergic and GABAergic neurons in the OB but not in the DG, while EPN-DBS does not impact neurogenesis. These effects do not seem to be mediated via direct electric stimulation of neural stem/progenitor cells within the neurogenic niches. Discussion: Our data support target-specific effects of STN-DBS on adult neurogenesis, a putative modulator of non-motor symptoms in Parkinson's disease.

Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer's disease (DEBBIE-AD): a prospective observational multicohort study protocol.

INTRODUCTION: Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer's disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). METHODS AND ANALYSIS: DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies. ETHICS AND DISSEMINATION: Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

Effects of obstructive sleep apnea treatment on neurodegenerative biomarker neurofilament light chain and cognitive performance.

Obstructive sleep apnea is associated with cognitive impairment and increased risk for neurodegenerative diseases. Obstructive sleep apnea treatment with positive airway pressure therapy helps to improve cognitive symptoms and reduces long-term dementia risk. To test whether these treatment effects are due to a reduction in neuronal damage, we examined longitudinal changes in the neurodegenerative serum neurofilament light chain and cognitive performance of patients with obstructive sleep apnea. In this study, 17 patients with obstructive sleep apnea completed baseline and follow-up (9 month after starting PAP treatment) investigation of sleep, daytime symptoms, cognitive testing and serum neurofilament light chain measurements. Depending on treatment adherence and efficacy, participants were assigned either to the effective treatment (n = 10) or non-effective treatment group (n = 7). As results at baseline lower mean oxygen saturation during sleep was associated with higher serum neurofilament light chain. Patients in the non-effective treatment group showed a significant increase of age-adjusted percentile of serum neurofilament light chain levels at follow-up, whereas serum neurofilament light chain values remained constant in the effective treatment group. At a functional level, effective treatment leads to an improvement in processing speed, which was not the case in the non-effective treatment group. Longitudinal changes of age-adjusted serum neurofilament light chain levels were associated with changes in cognitive performance. To conclude, this longitudinal observational study showed that effective obstructive sleep apnea treatment positively affects the amount of neuronal damage as well as working memory performance. As cognitive symptoms might not only be attributed to obstructive sleep apnea-related sleep deficiency, but also neurodegeneration, our results underline the importance of treatment adherence and efficacy for the prevention of neuronal damage and cognitive consequences.

The comorbidity profiles and medication issues of patients with multiple system atrophy: a systematic cross-sectional analysis.

BACKGROUND: Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients' safety and management. OBJECTIVES: To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients. METHODS: Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®. RESULTS: The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue. CONCLUSIONS: MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients.

The comorbidity and co-medication profile of patients with progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. OBJECTIVES: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease. METHODS: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik®. RESULTS: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions. CONCLUSIONS: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients.

[New Therapeutic Approaches for Chronic Insomnia]. / Neue Therapieansätze bei chronischer Insomnie.

Insomnia represents one of the most common syndromes with far-reaching health and socioeconomic consequences. After a long period of stagnation, recent years have seen promising advances in the nonpharmacological and pharmacological treatment of patients with chronic insomnia. This article highlights these new therapeutic approaches in the context of established treatment options.

Comorbid cerebral amyloid angiopathy in dementia and prodromal stages-Prevalence and effects on cognition.

OBJECTIVES: To determine the contribution of cerebral amyloid angiopathy to cognitive impairment in MCI and dementia. METHODS: Patients with subjective memory impairment (SMI), amnestic and non-amnestic mild cognitive impairment ((n)aMCI), Alzheimer's disease (AD), mixed and vascular dementia (MD/VD) from our memory clinic were included in this retrospective analysis. Patients underwent neuropsychological testing and cranial magnetic resonance imaging (MRI). Magnetic resonance imaging data sets were analyzed regarding the presence of CAA-related MRI biomarkers to determine CAA prevalence. ANOVAs were used to investigate the contribution of CAA to cognitive impairment within diagnostic groups and to determine whether differences in cognitive test performance between the diagnostic groups are mediated by total CAA burden. RESULTS: 475 patients (222 male, 253 female) with SMI (n = 47), naMCI (n = 41), aMCI (n = 189), early AD (n = 9), AD (n = 114), MD (n = 71) and VD (n = 4) were included. Mean age was 73.2 (9.9) years. CAA prevalence was 14.9% in SMI, 14.6% in naMCI, 24.3% in aMCI, 22.2% in early onset AD, 18.4% in late onset AD, 46.5% in MD and 25% in VD. Patients with possible and probable CAA were older than patients without CAA. In particular, diagnosis of aMCI, early onset AD, MD and VD showed high CAA prevalence. In AD but not in aMCI, CAA diagnosis significantly influenced test performance in the CERAD word list recall (F (1,78) = 4505; p = 0.037; partial eta-square = 0.055). Differences in cognitive test performance between the diagnostic groups of naMCI, aMCI, AD and MD were mediated by total CAA burden within AAT simply nouns subtest (F (2,39) = 4059; p = 0.025; partial eta-square = 0.172) and in CERAD verbal fluency test (F (3,129) = 3533; p = 0.017; partial eta-square = 0.076). CONCLUSION: This retrospective analysis demonstrates high prevalence rates of CAA in cognitive diagnoses. Our data suggest that comorbid CAA independently impacts cognitive test performance in the course of AD with presumably stage-dependent effects. Especially in patients with AD comorbid CAA additionally impairs memory function. Total CAA small vessel disease burden further modulates psychometric differences in cognitive test performance between diagnostic groups regarding word finding and word fluency capabilities.

[Coincidence of normal pressure hydrocephalus and Alzheimer`s disease: therapeutic implications and open questions]. / Zur Koinzidenz von Normaldruckhydrocephalus und Alzheimer-Demenz: therapeutische Implikationen und offene Fragen.

Normal pressure hydrocephalus (NPH) is prevalent in aging patient populations. Despite its clinical relevance, many patients with NPH may not receive adequate treatment. Because of the frequency of Alzheimer`s disease in these patients, there could be overlapping pathophysiological mechanisms that are as yet incompletely understood. Cerebral comorbidities seem to have negative effects on therapeutic response to ventriculoperitoneal shunting. In order to avoid unnecessary and unsuccessful surgery in highly vulnerable elderly patients, they have to be taken into consideration in the diagnostic process.

Targeting myeloid cell coagulation signaling blocks MAP kinase/TGF-ß1-driven fibrotic remodeling in ischemic heart failure.

Despite major advances in acute interventions for myocardial infarction (MI), adverse cardiac remodeling and excess fibrosis after MI causing ischemic heart failure (IHF) remain a leading cause of death worldwide. Here we identify a profibrotic coagulation signaling pathway that can be targeted for improved cardiac function following MI with persistent ischemia. Quantitative phosphoproteomics of cardiac tissue revealed an upregulated mitogen-activated protein kinase (MAPK) pathway in human IHF. Intervention in this pathway with trametinib improves myocardial function and prevents fibrotic remodeling in a murine model of non-reperfused MI. MAPK activation in MI requires myeloid cell signaling of protease-activated receptor 2 linked to the cytoplasmic domain of the coagulation initiator tissue factor (TF). They act upstream of pro-oxidant NOX2 NADPH oxidase, ERK1/2 phosphorylation, and activation of profibrotic TGF-ß1. Specific targeting with the TF inhibitor nematode anticoagulant protein c2 (NAPc2) starting 1 day after established experimental MI averts IHF. Increased TF cytoplasmic domain phosphorylation in circulating monocytes from patients with subacute MI identifies a potential thromboinflammatory biomarker reflective of increased risk for IHF and suitable for patient selection to receive targeted TF inhibition therapy.

Potential of Non-Coding RNA as Biomarkers for Progressive Supranuclear Palsy.

Objective markers for the neurodegenerative disorder progressive supranuclear palsy (PSP) are needed to provide a timely diagnosis with greater certainty. Non-coding RNA (ncRNA), including microRNA, piwi-interacting RNA, and transfer RNA, are good candidate markers in other neurodegenerative diseases, but have not been investigated in PSP. Therefore, as proof of principle, we sought to identify whether they were dysregulated in matched serum and cerebrospinal fluid (CSF) samples of patients with PSP. Small RNA-seq was undertaken on serum and CSF samples from healthy controls (n = 20) and patients with PSP (n = 31) in two cohorts, with reverse transcription-quantitative PCR (RT-qPCR) to confirm their dysregulation. Using RT-qPCR, we found in serum significant down-regulation in hsa-miR-92a-3p, hsa-miR-626, hsa-piR-31068, and tRNA-ValCAC. In CSF, both hsa-let-7a-5p and hsa-piR-31068 showed significant up-regulation, consistent with their changes observed in the RNA-seq results. Interestingly, we saw no correlation in the expression of hsa-piR-31068 within our matched serum and CSF samples, suggesting there is no common dysregulatory mechanism between the two biofluids. While these changes were in a small cohort of samples, we have provided novel evidence that ncRNA in biofluids could be possible diagnostic biomarkers for PSP and further work will help to expand this potential.

A pragmatic methodical framework for the user-centred development of an electronic process support for the sleep laboratory patients' management.

Objective: Limited capacities and ineffective care pathways result in long waiting times for patients and sporadic treatment controls in sleep medicine. As one objective of the 'Telesleep Medicine' project, a portal should be developed, which supports sleep specialists in an efficient and resource-saving patient management. On account of the limited project timeframe, the 'classical' user-centred design and evaluation methods could not be comprehensively implemented. Therefore, a pragmatic methodical framework was developed. Methods: For the iterative development of the portal, a combination of low-cost and quick-to-implement methods was used. In chronological order, these were: context interviews, personas, the development of an as-is model, a web search of design standards and good design aspects of similar systems, the development of a to-be model, the creation of an overarching mind map, and the iterative creation of mockups with simplified usability walkthroughs. Results: The feasibility of the pragmatic methodological framework for the development of a prototype for the portal was demonstrated. The used method combination resulted in a prototype based on the needs and requirements of the sleep specialists, taking into account their specific workflow and the technical implementation conditions. Conclusions: The presented pragmatic methodological framework can be a valuable resource for developers of comparable projects. The combination of methods worked well together regarding the limited timeframe and resources for concept development. For the future, we plan to implement and test the portal in the clinical field and thus enrich our framework with additional methods.

Use of intravascular ultrasound for optimal vessel sizing in chronic total occlusion percutaneous coronary intervention.

Aim: The aim of this study is to provide evidence on how use of standardized intravascular ultrasound (IVUS) use impacts stent size choice in the setting of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) compared to visual estimation. Methods and results: Data of 82 consecutive patients who had successfully undergone IVUS-guided revascularization of CTO at the University Medical Center Mainz were analyzed. Angiography-based stent size prediction for the proximal and distal vessels was compared to the implanted stent diameter after IVUS assessment. Angiography-based stent size prediction for the proximal vessel was 3.09 ± 0.41, whereas IVUS use demonstrated larger vessel diameter, resulting in larger implanted stent diameter (3.24 ± 0.45, p < 0.001). Proximal vessel stent size prediction was underestimated in the majority of patients by angiographic estimation. Angiography-based stent size prediction for the distal vessel was 2.79 ± 0.38, whereas IVUS use demonstrated larger vessel diameter, resulting in larger implanted stent diameter (2.92 ± 0.39, p < 0.001). Conclusion: Pre-stent IVUS assessment in CTO PCI provides important information on vessel morphology and size. Angiography-based stent size prediction for the proximal and distal vessels was frequently underestimated, IVUS use demonstrated larger vessel diameter, resulting in significantly larger implanted stent diameter.

Telomere Shortening in Hypertensive Heart Disease Depends on Oxidative DNA Damage and Predicts Impaired Recovery of Cardiac Function in Heart Failure.

BACKGROUND: Heart failure (HF) coincides with cardiomyocyte telomere shortening. Arterial hypertension is the most prominent risk factor for HF. Both HF and arterial hypertension are associated with dysregulation of the neurohormonal axis. How neurohormonal activation is linked to telomere shortening in the pathogenesis of HF is incompletely understood. METHODS: Cardiomyocyte telomere length was assessed in a mouse model of hypertensive HF induced by excess neurohormonal activation (AngII [angiotensin II] infusion, high salt diet, and uninephrectomy), in AngII-stimulated cardiomyocytes and in endomyocardial biopsies from patients with HF. Superoxide production, expression of NOX2 (NADPH oxidase 2) and PRDX1 (peroxiredoxin 1) and HDAC6 (histone deacetylase 6) activity were assessed. RESULTS: Telomere shortening occurred in vitro and in vivo, correlating with both left ventricular (LV) dilatation and LV systolic function impairment. Telomere shortening coincided with increased superoxide production, increased NOX2 expression, increased HDAC6 activity, loss of the telomere-specific antioxidant PRDX1, and increased oxidative DNA-damage. NOX2 knockout prevented PRDX1 depletion, DNA-damage and telomere shortening confirming this enzyme as a critical source of reactive oxygen species. Cotreatment with the NOX inhibitor apocynin ameliorated hypertensive HF and telomere shortening. Similarly, treatment with the HDAC6 inhibitor tubastatin A, which increases PRDX1 bioavailability, prevented telomere shortening in adult cardiomyocytes. To explore the clinical relevance of our findings, we examined endomyocardial biopsies from an all-comer population of patients with HF with reduced ejection fraction. Here, cardiomyocyte telomere length predicted the recovery of cardiac function. CONCLUSIONS: Cardiomyocyte telomere shortening and oxidative damage in heart failure with reduced ejection fraction induced by excess neurohormonal activation depends on NOX2-derived superoxide and may help to stratify HF therapy.

Training with Odors Impacts Hippocampal Thickness in Patients with Mild Cognitive Impairment.

BACKGROUND: The olfactory system is affected early in Alzheimer's disease and olfactory loss can already be observed in patients with mild cognitive impairment (MCI). Olfactory training is effective for improving olfactory and cognitive function by stimulating the olfactory pathway, but its effect on patients with MCI remains unclear. OBJECTIVE: The aim of this randomized, prospective, controlled, blinded study was to assess whether a 4-month period of olfactory training (frequent short-term sniffing various odors) may have an effect on olfactory function, cognitive function, and morphology of medial temporal lobe (MTL) subregions and olfactory bulb in MCI patients. METHODS: A total of thirty-seven MCI patients were randomly assigned to the training group or a placebo group, which were performed twice a day for 4 months. Olfactory assessments, cognitive tests and magnetic resonance imaging were performed at the baseline and follow-up period. RESULTS: After the training, there was an increase in odor discrimination, and increased cortical thickness of bilateral hippocampus (CA23DG and CA1) and mean MTL. Additionally, the change of olfactory score was positively associated with change of volume of olfactory bulb and hippocampus; the change of global cognition was positively associated with change of cortical thickness of hippocampus, entorhinal cortex and mean MTL; the change of cortical thickness of entorhinal cortex was positively associated with change of executive function. CONCLUSION: Olfactory training was associated with an increase in cortical thickness of the hippocampus but not olfactory bulb volume in patients with MCI. Olfactory training may serve as an early intervention of preventing hippocampal atrophy.

Percutaneous coronary intervention for chronic total occlusion in octogenarians: a propensity score study.

Feasibility and efficacy of complex percutaneous coronary intervention (PCI) in the elderly, a more frail population due to more comorbidities is incompletely understood. We therefore set out to compare success and complication rate of PCI for chronic total occlusion (CTO) in octogenarians, in comparison to non-octogenarians. Data from 267 patients (58 patients over 80 years of age and 209 under 80 years of age) who had undergone CTO PCI were analyzed. To compare the results we calculated the propensity score and used inverse probability of treatment weighting. We evaluated demographic, clinical, angiographic, and periprocedural information. The median age of the total collective was 68 (31-90) years (octogenarian collective 82 (80-90) years vs non-octogenarians 65 (31-79) years). We observed a high success rate in both collectives (82.8% vs 90.4%, p = 0.10) and no difference in periprocedural complications or complications in the follow-up period. In our collective restenosis rate at follow-up was comparable to the propensity sore weighted population (11.3% vs 16.3%, p = 0.9). Our results show that CTO PCI in older patients is safe and feasible with comparable in-hospital and follow-up complication rates compared to a younger patient population.

Predictors of subjective cognitive deficits in patients with mild cognitive impairment.

BACKGROUND: Detailed examination of cognitive deficits in patients with mild cognitive impairment (MCI) yields substantial diagnostic and prognostic value, specifically with respect to memory. Magnitude and characteristics of subjective cognitive deficits, however, often receive less attention in this population at risk for developing dementia. METHODS: We investigated predictors of subjective cognitive deficits in patients with MCI, using a detailed assessment for such impairments associated with different cognitive domains, as well as demographic and clinical variables including magnetic resonance imaging data. RESULTS: The strongest predictor for subjective memory deficits was depressed mood, whereas subjective performance issues associated with attention or executive functions also corresponded to measurable impairments in the respective cognitive domains. Reduced hippocampal thickness and hemispheric entorhinal cortex thickness asymmetry were associated with objective memory impairment but not with subjective deficits or symptoms of depression. CONCLUSIONS: Whereas low objective memory performance and reduced cortical thickness within medial temporal lobe subregions could be associated with neurodegeneration, greater subjective memory deficits in patients with MCI may indicate psychological burden.

Effectiveness of a Real-Time X-ray Dosimetry Monitor in Reducing Radiation Exposure in Coronary Procedures: The ESPRESSO-Raysafe Randomized Trial.

Background-Several methods to reduce radiation exposure in the setting of coronary procedures are available on the market, and we previously showed that additional radiation shields reduce operator exposure during radial interventions. We set out to examine the efficacy of real-time personal dosimetry monitoring in a real-world setting of radial artery catheterization. Methods and Results-In an all-comer prospective, parallel study, consecutive coronary diagnostic and intervention procedures were performed with the use of standard radiation shield alone (control group) or with the addition of a real-time dosimetry monitoring system (Raysafe, Billdal, Sweden, monitoring group). The primary outcome was the difference in exposure of the primary operator among groups. Additional endpoints included patient, nurse, second operator exposure and fluoroscopy time. A total of 700 procedures were included in the analysis (n = 369 in the monitoring group). There were no differences among groups in patients' body mass index (p = 0.232), type of procedure (intervention vs. diagnostic, p = 0.172), and patient sex (p = 0.784). Fluoroscopy time was shorter in the monitoring group (5.6 (5.1-6.2) min vs. 7.0 (6.1-7.7) min, p = 0.023). Radiation exposure was significantly lower in the monitoring group for the patient (135 (115-151) µSv vs. 208 (176-245) µSv, p < 0.0001) but not for the first operator (9 (7-11) µSv vs. 10 (8-11), p = 0.70) and the assistant (2 (1-2) µSv vs. 2 (1-2) µSv, p = 0.121). Conclusions-In clinical daily practice, the use of a real-time dosimetry monitoring device reduces patient radiation exposure and fluoroscopy time without an effect on operator radiation exposure.

Adult Neural Stem Cells from Midbrain Periventricular Regions Show Limited Neurogenic Potential after Transplantation into the Hippocampal Neurogenic Niche.

The regulation of adult neural stem or progenitor cell (aNSC) proliferation and differentiation as an interplay of cell-intrinsic and local environmental cues remains in part unclear, impeding their role in putative regenerative therapies. aNSCs with all major properties of NSCs in vitro have been identified in a variety of brain regions beyond the classic neurogenic niches, including the caudal periventricular regions (PVRs) of the midbrain, though active neurogenesis is either limited or merely absent in these regions. To elucidate cell-intrinsic properties of aNSCs from various PVRs, we here examined the proliferation and early differentiation capacity of murine aNSCs from non-neurogenic midbrain PVRs (PVRMB) compared to aNSCs from the neurogenic ventricular-subventricular zone (PVRV-SVZ) 7 days after transplantation into the permissive pro-neurogenic niche of the dentate gyrus (DG) of the hippocampus in mice. An initial in vitro characterization of the transplants displayed very similar characteristics of both aNSC grafts after in vitro expansion with equal capacities of terminal differentiation into astrocytes and Tuj1+ neurons. Upon the allogenic transplantation of the respective aNSCs into the DG, PVRMB grafts showed a significantly lower graft survival and proliferative capacity compared to PVRV-SVZ transplants, whereby the latter are exclusively capable of generating new neurons. Although these differences might be-in part-related to the transplantation procedure and the short-term study design, our data strongly imply important cell-intrinsic differences between aNSCs from neurogenic compared to non-neurogenic PVRs with respect to their neurogenic potential and/or their sensitivity to neurogenic cues.