Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have ...functional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear-bomb-test-derived 14C in genomic DNA, and we present an integrated model of the cell turnover dynamics. We found that a large subpopulation of hippocampal neurons constituting one-third of the neurons is subject to exchange. In adult humans, 700 new neurons are added in each hippocampus per day, corresponding to an annual turnover of 1.75% of the neurons within the renewing fraction, with a modest decline during aging. We conclude that neurons are generated throughout adulthood and that the rates are comparable in middle-aged humans and mice, suggesting that adult hippocampal neurogenesis may contribute to human brain function.
Display omitted
•Nuclear-bomb-test-derived 14C in human hippocampal neurons reveals adult neurogenesis•One-third of hippocampal neurons are subject to exchange•The annual turnover rate is 1.75% within the renewing fraction in adult humans•The extent of adult neurogenesis is comparable in middle-aged humans and mice
14C dating shows that in the human hippocampus neurons are continually added throughout adulthood at a rate of 700 new neurons per day, implicating neurogenesis in human cognitive plasticity.
The neocortex is the seat of higher cognitive functions and, in evolutionary terms, is the youngest part of the mammalian brain. Since its origin, the neocortex has expanded in several mammalian ...lineages, and this is particularly notable in humans. This expansion reflects an increase in the number of neocortical neurons, which is determined during development and primarily reflects the number of neurogenic divisions of distinct classes of neural progenitor cells. Consequently, the evolutionary expansion of the neocortex and the concomitant increase in the numbers of neurons produced during development entail interspecies differences in neural progenitor biology. Here, we review the diversity of neocortical neural progenitors, their interspecies variations and their roles in determining the evolutionary increase in neuron numbers and neocortex size.
Neural stem and progenitor cells have a central role in the development and evolution of the mammalian neocortex. In this review, we first provide a set of criteria to classify the various types of ...cortical stem and progenitor cells. We then discuss the issue of cell polarity, as well as specific subcellular features of these cells that are relevant for their modes of division and daughter cell fate. In addition, cortical stem and progenitor cell behavior is placed into a tissue context, with consideration of extracellular signals and cell-cell interactions. Finally, the differences across species regarding cortical stem and progenitor cells are dissected to gain insight into key developmental and evolutionary mechanisms underlying neocortex expansion.
Background: Intracerebral hemorrhage (ICH) accounts for up to 15% of all strokes and
is characterized by high rates of mortality and morbidity. The post-ICH brain injury can be distinguished
in 1) ...primary, which are caused by disruption and mechanical deformation of brain tissue
due to hematoma growth and 2) secondary, which are induced by microglia activation, mitochondrial
dysfunction, neurotransmitter and inflammatory mediator release. Although these events typically
lead to necrosis, the occurrence of programmed cell death has also been reported after ICH.
Methods: We reviewed recent publications describing advance in pre- and clinic ICH research.
Results: At present, treatment of ICH patients is based on oral anticoagulant reversal, management
of blood pressure and other medical complications. Several pre-clinical studies showed promising
results and demonstrated that anti-oxidative and anti-inflammatory treatments reduced neuronal cell
death, however, to date, all of these attempts have failed in randomized controlled clinical trials.
Yet, the time frame of administration may be crucial in translation from animal to clinical studies.
Furthermore, the latest pre-clinical research points toward the existence of other, apoptosisunrelated
forms kinds of programmed cell death.
Conclusion: Our review summarizes current knowledge of pathways leading to programmed cell
death after ICH in addition to data from clinical trials. Some of the pre-clinical results have not yet
demonstrated clinical confirmation, however they significantly contribute to our understanding of
post-ICH pathology and can contribute to development of new therapeutic approaches, decreasing
mortality and improving ICH patients’ quality of life.
During development, both cells and tissues must acquire the correct shape to allow their proper function. This is especially relevant in the nervous system, where the shape of individual cell ...processes, such as the axons and dendrites, and the shape of entire tissues, such as the folding of the neocortex, are highly specialized. While many aspects of neural development have been uncovered, there are still several open questions concerning the mechanisms governing cell and tissue shape. In this review, we discuss the role of the extracellular matrix (ECM) in these processes. In particular, we consider how the ECM regulates cell shape, proliferation, differentiation and migration, and more recent work highlighting a key role of ECM in the morphogenesis of neural tissues.
Primary cilia are key sensory organelles that are thought to be disassembled prior to mitosis. Inheritance of the mother centriole, which nucleates the primary cilium, in relation to asymmetric ...daughter cell behavior has previously been studied. However, the fate of the ciliary membrane upon cell division is unknown. Here, we followed the ciliary membrane in dividing embryonic neocortical stem cells and cultured cells. Ciliary membrane attached to the mother centriole was endocytosed at mitosis onset, persisted through mitosis at one spindle pole, and was asymmetrically inherited by one daughter cell, which retained stem cell character. This daughter re-established a primary cilium harboring an activated signal transducer earlier than the noninheriting daughter. Centrosomal association of ciliary membrane in dividing neural stem cells decreased at late neurogenesis when these cells differentiate. Our data imply that centrosome-associated ciliary membrane acts as a determinant for the temporal-spatial control of ciliogenesis.
Display omitted
•Primary cilium is not fully disassembled prior to mitosis•Ciliary membrane can remain attached to mother centriole throughout mitosis•Asymmetric inheritance of ciliary remnant underlies earlier cilium reformation•Centrosomal association of ciliary membrane changes during neocortical development
It has been thought that the primary cilium is completely disassembled prior to mitosis. Ciliary membrane now has been shown to remain attached to the mother centriole throughout mitosis in somatic cells. This ciliary remnant is asymmetrically inherited by one daughter cell, which regrows a functional cilium before its sister cell does.
Neocortical expansion, thought to underlie the cognitive traits unique to humans, is accompanied by cortical folding. This folding starts around gestational week (GW) 20, but what causes it remains ...largely unknown. Extracellular matrix (ECM) has been previously implicated in neocortical expansion and here we investigate the potential role of ECM in the formation of neocortical folds. We focus on three specific ECM components localized in the human fetal cortical plate (CP): hyaluronan and proteoglycan link protein 1 (HAPLN1), lumican and collagen I (collectively, HLC). Addition of HLC to cultures of human fetal neocortex (11–22 GW) caused local changes in tissue stiffness, induced CP folding, increased CP hyaluronic acid (HA), and required the HA-receptor CD168 and downstream ERK signaling. Importantly, loss of HA reduced HLC-induced and 22 GW physiological nascent folds. This was altered in samples with neurodevelopmental disorders, indicating it may be a useful system to study such disorders.
Display omitted
•ECM components HAPLN1, lumican and collagen I (HLC) induce human neocortex folding•HLC-induced folding involves increases in ECM stiffness and requires HA/CD168/ERK•Degradation of HA reduces physiological folds in 22 GW human neocortex•HLC-induced cortical folding is impaired in certain neurodevelopmental disorders
Folding of the human neocortex is a key feature of its evolutionary expansion. Here, Long et al. identify a novel extracellular matrix-driven mechanism underlying human neocortex folding, and disruption of this mechanism perturbs the physiological folding of human neocortical tissue.
What is antimicrobial stewardship? Dyar, O.J.; Huttner, B.; Schouten, J. ...
Clinical microbiology and infection,
11/2017, Letnik:
23, Številka:
11
Journal Article
Recenzirano
Odprti dostop
The use of the term ‘antimicrobial stewardship’ has grown exponentially in recent years, typically referring to programmes and interventions that aim to optimize antimicrobial use. Although ...antimicrobial stewardship originated within human healthcare, it is increasingly applied in broader contexts including animal health and One Health. As the use of the term ‘antimicrobial stewardship’ becomes more common, it is important to consider what antimicrobial stewardship is, as well as what it is not.
To review the emergence and evolution of the term ‘antimicrobial stewardship’.
We searched and reviewed existing literature and official documents, which mostly focused on antibiotics. We contacted the authors of the first publications that mentioned antimicrobial stewardship.
We describe the historical background behind how antimicrobial stewardship came into use in clinical settings. We discuss challenges emerging from the varied descriptions of antimicrobial stewardship in the literature, including an over-emphasis on individual prescriptions, an under-emphasis on the societal implications of antimicrobial use, and language translation problems.
To help address these challenges, we suggest viewing antimicrobial stewardship as a strategy, a coherent set of actions which promote using antimicrobials responsibly. We stress the continuous need for ‘responsible use’ to be defined and translated into context-specific and time-specific actions. Furthermore, we present examples of actions that can be undertaken within antimicrobial stewardship across human and animal health.
Cefepime remains an important antibiotic for severe bacterial infections, yet some meta-analyses have shown elevated mortality among patients randomized to it. Therapeutic drug monitoring (TDM) of ...β-lactam antibiotics is increasing, but optimal plasma concentrations remain unknown. We examined clinical outcomes of patients undergoing cefepime TDM in an initial effort to define the drug's toxicity threshold.
In this single-centre retrospective cohort study, we enrolled all adult hospitalized patients receiving cefepime and undergoing TDM from January 2013 through July 2016. The primary outcome was the incidence of clinical toxicity; a secondary outcome was clinical failure. Plasma samples were analysed via high-performance liquid chromatography with ultraviolet detection.
A total of 161 cefepime concentrations were drawn from 93 patients. Roughly half (82/161, 51%) and one-third (49/161, 30%) were trough and steady-state levels from patients receiving intermittent and continuous infusions, respectively; median concentrations were 17.6 mg/L (IQR 9.7-35.2) and 29.2 mg/L (IQR 18.9-45.9). Ten patients (11%) experienced a neurologic event considered at least possibly related to cefepime; neurotoxicity was associated with poorer renal function (median creatinine clearance 54 (IQR 39-97) vs. 75 mL/min/1.732 (IQR 44-104)) and longer cefepime durations (mean 8.3 (SD±6.7) vs. 13.3 days (± 14.2), p = 0.071). Patients with trough levels >20 mg/L had a fivefold higher risk for neurologic events (OR 5.05, 95% CI 1.3-19.8).
Neurotoxicity potentially related to cefepime occurred at plasma concentrations >35 mg/L. For those receiving intermittent infusions, trough concentrations >20 mg/L should be avoided until further information is available from prospective studies.
PDF
