Adult neural stem cells (NSCs) are believed to facilitate CNS repair and tissue regeneration. However, it is not yet clear how these cells are influenced when the cellular environment is modified during neurotrauma or neuroinflammatory conditions. In this study, we determine how different proinflammatory cytokines modulate the expression of TLR2 and TLR4 in NSCs and how these cells respond to TLR2 and TLR4 agonists. Primary cultures of neural stem/progenitor cells isolated from the subventricular zone of brains from adult Dark Agouti rats were exposed to 1) supernatants from activated macrophages; 2) proinflammatory cytokines IFN-gamma, TNF-alpha, or both; and 3) agonists for TLR2 and TLR4. Both TLR2 and TLR4 were expressed during basal conditions and their mRNA levels were further increased following cytokine exposure. TLR4 was up-regulated by IFN-gamma and this effect was reversed by TNF-alpha. TLR2 expression was increased by supernatants from activated macrophages and by TNF-alpha, which synergized with IFN-gamma. TLR agonists induced the expression of TNF-alpha mRNA. Importantly, TNF-alpha could be translated into protein and released into the supernatants where it was quantified by cytokine ELISA. In conclusion, we demonstrate that NSCs constitutively express TLR2 and TLR4 and that their expression is increased as a consequence of exposure to proinflammatory mediators. Additionally, activation of these receptors can induce production of proinflammatory cytokines. These findings suggest that NSCs may be primed to participate in cytokine production during neuroinflammatory or traumatic conditions.
OBJECTIVE The objective of this study was to describe the demographic characteristics of patients with idiopathic normal pressure hydrocephalus (iNPH) through an analysis of 3000 consecutive, surgically treated Swedish patients and a systematic review of the literature. METHODS Data on age, sex, comorbidities, diagnostic delay, initial symptoms, and severity of symptoms at diagnosis were extracted from the Swedish Hydrocephalus Quality Registry. In addition, a systematic PRISMA-based review of the literature published from database inception until August 2019 was performed using the PubMed, Cochrane, and Scopus databases on the basis of two concepts: normal pressure hydrocephalus and demography and their association with related terms. Of 1020 unique articles, 16 were eligible for study inclusion and were assessed for quality using the Newcastle-Ottawa Scale. Mean and weighted mean values were calculated. RESULTS The mean patient age at the time of surgery was 74.4 years, 79% of patients were in their 70s, and 60% of the patients were men. Almost 50% of the patients had symptoms from four main domains (i.e., balance, gait, cognition, and urinary dysfunction) at disease onset. Patients aged < 60 years (2%) reported more headaches and fewer balance problems than those aged ≥ 60. Women were more impaired in function than men at the time of diagnosis. Dementia (Mini-Mental State Examination score < 25) was found in 47% of the patients. Men had more diabetes, heart disease, hypertension, and stroke than women, and comorbidity correlated with increased impairment. The incidence of surgery for iNPH was 20%–40% of the disease incidence according to survey and operation-based studies. CONCLUSIONS Most iNPH patients undergo surgery in their 70s. Those aged < 60 years show slightly different symptomatology and probably present with a specific disease entity, indicating that the lower age limit for iNPH should be 60 years. iNPH patients have severe impairment preceded by a long diagnostic delay. Even though the included study designs differed, the systematic review showed that the disorder has a very low treatment incidence. The importance of diagnosing and treating iNPH is further emphasized by the fact that iNPH may account for a considerable part of all cases of dementia.
BackgroundFilum terminale (FT) is a structure that is intimately associated with conus medullaris, the most caudal part of the spinal cord. It is well documented that certain regions of the adult human central nervous system contains undifferentiated, progenitor cells or multipotent precursors. The primary objective of this study was to describe the distribution and progenitor features of this cell population in humans, and to confirm their ability to differentiate within the neuroectodermal lineage.Methodology/Principal FindingsWe demonstrate that neural stem/progenitor cells are present in FT obtained from patients treated for tethered cord. When human or rat FT-derived cells were cultured in defined medium, they proliferated and formed neurospheres in 13 out of 21 individuals. Cells expressing Sox2 and Musashi-1 were found to outline the central canal, and also to be distributed in islets throughout the whole FT. Following plating, the cells developed antigen profiles characteristic of astrocytes (GFAP) and neurons (β-III-tubulin). Addition of PDGF-BB directed the cells towards a neuronal fate. Moreover, the cells obtained from young donors shows higher capacity for proliferation and are easier to expand than cells derived from older donors.Conclusion/SignificanceThe identification of bona fide neural progenitor cells in FT suggests a possible role for progenitor cells in this extension of conus medullaris and may provide an additional source of such cells for possible therapeutic purposes.Filum terminale, human, progenitor cells, neuron, astrocytes, spinal cord.
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