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1.
EMBO J ; 43(3): 317-338, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38177500

RESUMO

Lifelong hippocampal neurogenesis is maintained by a pool of multipotent adult neural stem cells (aNSCs) residing in the subgranular zone of the dentate gyrus (DG). The mechanisms guiding transition of NSCs from the developmental to the adult state remain unclear. We show here, by using nestin-based reporter mice deficient for cyclin D2, that the aNSC pool is established through cyclin D2-dependent proliferation during the first two weeks of life. The absence of cyclin D2 does not affect normal development of the dentate gyrus until birth but prevents postnatal formation of radial glia-like aNSCs. Furthermore, retroviral fate mapping reveals that aNSCs are born on-site from precursors located in the dentate gyrus shortly after birth. Taken together, our data identify the critical time window and the spatial location of the precursor divisions that generate the persistent population of aNSCs and demonstrate the central role of cyclin D2 in this process.


Assuntos
Células-Tronco Neurais , Neurônios , Animais , Camundongos , Ciclina D2/genética , Giro Denteado , Hipocampo , Neurogênese
2.
Int J Med Microbiol ; 311(4): 151500, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33813306

RESUMO

BACKGROUND: The number of people above the age of 60 years is raising world-wide being associated with an increase in the prevalence of aging-associated impairments and even diseases. Recent studies suggest that aging is associated with alterations in bacterial endotoxin levels and that these changes may add to low-grade inflammation, the so-called 'inflammaging', and aging-associated liver degeneration. However, mechanisms involved, and especially, the interaction of intestinal microbiota and barrier in the development of aging-associated inflammation and liver degeneration have not been fully understood. OBJECTIVE: The aim of the present study was to determine if intestinal microbiota composition changes with age and if these alterations are associated with changes of markers of intestinal barrier function and the development of inflammation and liver degeneration. METHODS: Blood, liver, small and large intestinal tissue of male 2-, 15-, 24- and 30-months old C57BL/6 mice fed standard chow were obtained. Intestinal microbiota composition, expression levels of antimicrobial peptides in small intestine and markers of intestinal barrier function were measured. Furthermore, indices of liver damage, inflammation and expression levels of lipopolysaccharide binding protein (Lbp) as well as of toll-like receptors (Tlr) 1-9 in liver tissue were assessed. RESULTS: Pairwise comparisons of the microbial community in the small intestine showed differences between 2- and 24-, 15- and 24-, as well as 15- and 30-months old animals while Shannon's diversity, species richness and evenness indexes did not differ in both small and large intestine, respectively, between age groups. Concentrations of nitric oxide were significantly lower in small intestine of 15-, 24- and 30-months old mice compared to 2-months old mice while mRNA expression of the antimicrobial peptides defensin alpha 1 and lysozyme 1 was unchanged. In contrast, in liver tissue, older age of animals was associated with increasing inflammation and the development of fibrosis in 24- and 30-months old mice. Numbers of inflammatory foci and neutrophils in livers of 24- and 30-months old mice were significantly higher compared to 2-months old mice. These alterations were also associated with higher endotoxin levels in plasma as well as an increased mRNA expression of Lbp and Tlr1, Tlr2, Tlr4, Tlr6 and Tlr9 in livers in older mice. CONCLUSION: Despite no consistent and robust changes of microbiota composition in small and/or large intestine of mice of different age were observed, our data suggest that alterations of markers of intestinal barrier function in small intestine are associated with an induction of several Tlrs and beginning hepatic inflammation in older mice and increase with age.


Assuntos
Microbioma Gastrointestinal , Inflamação , Envelhecimento , Animais , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL
3.
Aesthet Surg J ; 41(6): NP609-NP615, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33367647

RESUMO

BACKGROUND: Botulinum toxin A (BTX), a neurotoxin widely used for facial aesthetics, causes dose-dependent muscle paralysis. It was hypothesized that treatment of mimic muscles with BTX might have a positive impact on emotional expression in static images (photographs), but a negative impact in dynamic recordings (videos). OBJECTIVES: The aim of this study was to compare of emotional expression recorded in photographs and videos before and after treatment with BTX. METHODS: Twenty healthy women (mean age, 45 years) received a dose of 19 mouse units of XEOMIN (Merz, Frankfurt am Main, Germany) into the procerus, occipitofrontalis, and orbicularis oculi muscles. Photographs and videos of the participants' faces with neutral and happy expressions were recorded before treatment and 2 weeks later. Recordings were rated by naive raters blind to the conditions and in balanced order. RESULTS: Videos were generally rated as more pleasant, arousing, attractive, and genuine than photographs (all Ps > 0.001). This was especially the case for videos with neutral expression (P = 0.003). Independent of presentation mode and facial expression, women were rated as more attractive after BTX treatment (P = 0.03). CONCLUSIONS: In contrast to the hypothesis, the reduced mobility had no detectable negative impact on dynamic emotional expression, but videos received more positive ratings, particularly for neutral expressions. It is thus recommended to assess emotional expression with dynamic recordings to evaluate the effects of treatment with BTX. BTX seems to improve perceived attractiveness, although the cause of this effect remains unclear.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Emoções , Expressão Facial , Músculos Faciais , Feminino , Felicidade , Humanos , Injeções , Pessoa de Meia-Idade , Estudos Prospectivos
4.
Circ Res ; 124(12): e101-e114, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-30947629

RESUMO

RATIONALE: Delayed ischemic neurological deficit is the most common cause of neurological impairment and unfavorable prognosis in patients with subarachnoid hemorrhage (SAH). Despite the existence of neuroimaging modalities that depict the onset of the accompanying cerebral vasospasm, preventive and therapeutic options are limited and fail to improve outcome owing to an insufficient pathomechanistic understanding of the delayed perfusion deficit. Previous studies have suggested that BOXes (bilirubin oxidation end products), originating from released heme surrounding ruptured blood vessels, are involved in arterial vasoconstriction. Recently, isolated intermediates of oxidative bilirubin degradation, known as PDPs (propentdyopents), have been considered as potential additional effectors in the development of arterial vasoconstriction. OBJECTIVE: To investigate whether PDPs and BOXes are present in hemorrhagic cerebrospinal fluid and involved in the vasoconstriction of cerebral arterioles. METHODS AND RESULTS: Via liquid chromatography/mass spectrometry, we measured increased PDP and BOX concentrations in cerebrospinal fluid of SAH patients compared with control subjects. Using differential interference contrast microscopy, we analyzed the vasoactivity of PDP isomers in vitro by monitoring the arteriolar diameter in mouse acute brain slices. We found an arteriolar constriction on application of PDPs in the concentration range that occurs in the cerebrospinal fluid of patients with SAH. By imaging arteriolar diameter changes using 2-photon microscopy in vivo, we demonstrated a short-onset vasoconstriction after intrathecal injection of either PDPs or BOXes. Using magnetic resonance imaging, we observed a long-term PDP-induced delay in cerebral perfusion. For all conditions, the arteriolar narrowing was dependent on functional big conductance potassium channels and was absent in big conductance potassium channels knockout mice. CONCLUSIONS: For the first time, we have quantified significantly higher concentrations of PDP and BOX isomers in the cerebrospinal fluid of patients with SAH compared to controls. The vasoconstrictive effect caused by PDPs in vitro and in vivo suggests a hitherto unrecognized pathway contributing to the pathogenesis of delayed ischemic deficit in patients with SAH.


Assuntos
Arteríolas/metabolismo , Bilirrubina/líquido cefalorraquidiano , Heme/líquido cefalorraquidiano , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Vasoconstrição/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Arteríolas/patologia , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Oxirredução , Hemorragia Subaracnóidea/patologia , Vasoespasmo Intracraniano/líquido cefalorraquidiano , Vasoespasmo Intracraniano/patologia
5.
Dtsch Med Wochenschr ; 141(17): 1244-9, 2016 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-27557073

RESUMO

Autoimmune encephalitis, an inflammatory disease of the brain, is usually attributed to antibody-mediated damage and dysfunction of neuronal structures. A distinction is made between onconeuronal antibodies (directed against intracellular neuronal antigens with resulting paraneoplastic neurological syndromes) and antibodies directed against neuronal cell surface proteins (with resulting synaptic encephalopathies). Anti-NMDA-Receptor-Encephalitis, the most common form of autoimmune encephalopathy, is characterized by a phased course of disease. Early disease phase involves nonspecific prodromes (fatigue, fever, headache) which lead to family doctor or emergency department consultation. Subsequently, neuropsychiatric behavioural problems, seizures, disturbance of memory and finally coma, dysautonomia and respiratory insufficiency often result in major complications (e.g. status epilepticus) necessitating intensive care treatment. The diagnosis is secured by detection of auto-antibodies in serum or cerebrospinal fluid. An intensive search for tumors is also recommended. The treatment of autoimmune encephalitis comprises of immunomodulatory and immunosuppessive strategies. Tumor therapy is the most important treatment of autoimmune encephalitis by onconeuronal antibodies.


Assuntos
Encefalite , Doença de Hashimoto , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Eletroencefalografia , Feminino , Humanos , Adulto Jovem
6.
J Am Heart Assoc ; 3(4)2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-25169792

RESUMO

BACKGROUND: Delayed cerebral vasospasm is the most common cause of mortality and severe neurological impairment in patients who survive subarachnoid hemorrhage. Despite improvements in the field of diagnostic imaging, options for prevention and medical treatment-primarily with the calcium channel antagonist nimodipine or hemodynamic manipulations-are insufficient. Previous studies have suggested that heme and bilirubin oxidation end products, originating from degraded hemoglobin around ruptured blood vessels, are involved in the development of vasospasm by inhibiting large conductance BKC a potassium channels in vascular smooth muscle cells. In this study, we identify individual heme degradation products regulating arteriolar diameter in dependence of BKC a channel activity. METHODS AND RESULTS: Using differential interference contrast video microscopy in acute brain slices, we determined diameter changes of intracerebral arterioles in mouse visual cortex. In preconstricted vessels, the specific BKC a channel blockers paxilline and iberiotoxin as well as iron-containing hemin caused vasoconstriction. In addition, the bilirubin oxidation end product Z-BOX A showed a stronger vasoconstrictive potency than its regio-isomer Z-BOX B. Importantly, Z-BOX A had the same vasoconstrictive effect, independent of its origin from oxidative degradation or chemical synthesis. Finally, in slices of Slo1-deficient knockout mice, paxilline and Z-BOX A remained ineffective in changing arteriole diameter. CONCLUSIONS: We identified individual components of the oxidative bilirubin degradation that led to vasoconstriction of cerebral arterioles. The vasoconstrictive effect of Z-BOX A and Z-BOX B was mediated by BKC a channel activity that might represent a signaling pathway in the occurrence of delayed cerebral vasospasm in subarachnoid hemorrhage patients.


Assuntos
Arteríolas/efeitos dos fármacos , Hemina/farmacologia , Indóis/farmacologia , Peptídeos/farmacologia , Vasoconstrição/efeitos dos fármacos , Córtex Visual/irrigação sanguínea , Animais , Arteríolas/patologia , Bilirrubina/metabolismo , Heme/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Alta/antagonistas & inibidores , Camundongos , Microscopia de Interferência , Bloqueadores dos Canais de Potássio , Pirróis , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/etiologia , Córtex Visual/efeitos dos fármacos
7.
J Med Case Rep ; 7: 24, 2013 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-23331641

RESUMO

INTRODUCTION: Unilateral hyperhidrosis can be a neurological manifestation of irritations of the central or peripheral nervous system. CASE PRESENTATION: We present the case of a 67-year-old German man who had hyperhidrosis of his right upper body quadrant (including face, arm, and chest) following intrathoracic surgery of a left-sided pleural lipoma. CONCLUSION: An isolated unilateral hyperhidrosis might occur after intrathoracic surgery. Besides anticholinergic drugs the use of botulinum toxin should be considered.

8.
Eur Arch Otorhinolaryngol ; 268(10): 1493-500, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21298392

RESUMO

This prospective study on Bell's palsy investigated the value of 3 T MRI as a diagnostic tool to evaluate pathophysiological changes (i.e. edema) of facial nerve segments and the possibility to differentiate patients with high risk for incomplete recovery from patients who recover completely within 3 days after symptoms onset. For this institutional review board approved investigation, thirty patients (14 male, 16 female, mean age 44 years) with Bell's palsy underwent pre and postcontrast 3 T MRI of the cerebellopontine angle. T1-weighted imaging was performed (TR 20.0 ms, TE 2.46 ms, isotropic voxel size: 0.6 mm). Region-of-interest measurements were performed on the healthy and paralyzed side. To obtain normalized values, signal intensity increase percentage (SIIP) values were divided by contralateral results of the healthy side. Signal intensity measurements of examined nerve segments were compared using Wilcoxon and Mann-Whitney U tests and correlated to clinical findings categorized by the House-Brackmann score. The lesion side showed significantly higher signal intensities in the premeatal segment before and after contrast agent administration (P < 0.001). SIIP was highest in the premeatal segment compared to the geniculate ganglion (P < 0.001). Correlation analyses revealed no association between signal intensity measurements, clinical findings or early recovery rates after 3 months (P > 0.05). According to our results, early palsy-associated pathophysiological changes in the facial nerve premeatal segment might also be related to accumulation of proteins and not exclusively to edema. However, contrast agent enhancement quantification was not suitable as a diagnostic tool to distinguish different prognostic groups.


Assuntos
Paralisia de Bell/diagnóstico , Diagnóstico Precoce , Nervo Facial/patologia , Gânglio Geniculado/patologia , Imageamento Tridimensional , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Paralisia de Bell/fisiopatologia , Diagnóstico Diferencial , Nervo Facial/fisiopatologia , Feminino , Seguimentos , Gânglio Geniculado/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto Jovem
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