The age and genomic integrity of neurons after cortical stroke in humans

Huttner, Hagen B.; Bergmann, Olaf; Salehpour, Mehran; Rácz, A.; Tatarishvili, Jemal; Lindgren, Emma; Csonka, Tamás; Csiba, László; Hortobágyi, Tibor; Méhes, Gábor; Englund, Elisabet; Solnestam, Beata Werne; Zdunek, Sofia; Scharenberg, Christian; Ström, Lena; Ståhl, Patrik L.; Sigurgeirsson, Bárður; Dahl, Andreas; Schwab, Stefan; Possnert, Göran; Bernard, Samuel; Kokaia, Zaal; Lindvall, Olle; Lundeberg, Joakim; Frisén, Jonas

doi:10.1038/nn.3706

Cited by 111 publications

(111 citation statements)

References 26 publications

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“…Poststroke neurogenesis has been reported in human stroke, by utilizing tissue staining for protein markers of immature neurons in autopsy material 72, 73, 74. However, a lack of poststroke neurogenesis has been reported in human cortical stroke, using 14 C labeling of newly born cells 75. Both techniques have limitations in specificity and sensitivity, and may also miss a transient neurogenic response after stroke that is limited in size and then stopped 76, 77.…”

Section: The Brain Forms Regenerative Cellular Niches During Repair Amentioning

confidence: 99%

Emergent properties of neural repair: elemental biology to therapeutic concepts

Carmichael

2016

Annals of Neurology

118

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Stroke is the leading cause of adult disability. The past decade has seen advances in basic science research of neural repair in stroke. The brain forms new connections after stroke, which have a causal role in recovery of function. Brain progenitors, including neuronal and glial progenitors, respond to stroke and initiate a partial formation of new neurons and glial cells. The molecular systems that underlie axonal sprouting, neurogenesis, and gliogenesis after stroke have recently been identified. Importantly, tractable drug targets exist within these molecular systems that might stimulate tissue repair. These basic science advances have taken the field to its first scientific milestone; the elemental principles of neural repair in stroke have been identified. The next stages in this field involve understanding how these elemental principles of recovery interact in the dynamic cellular systems of the repairing brain. Emergent principles arise out of the interaction of the fundamental or elemental principles in a system. In neural repair, the elemental principles of brain reorganization after stroke interact to generate higher order and distinct concepts of regenerative brain niches in cellular repair, neuronal networks in synaptic plasticity, and the distinction of molecular systems of neuroregeneration. Many of these emergent principles directly guide the development of new therapies, such as the necessity for spatial and temporal control in neural repair therapy delivery and the overlap of cancer and neural repair mechanisms. This review discusses the emergent principles of neural repair in stroke as they relate to scientific and therapeutic concepts in this field. Ann Neurol 2016;79:895–906

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Section: The Brain Forms Regenerative Cellular Niches During Repair Amentioning

confidence: 99%

Emergent properties of neural repair: elemental biology to therapeutic concepts

Carmichael

2016

Annals of Neurology

118

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“…Studies that analyzed the incorporation of 14 C in the DNA of dividing cells observed no neurogenesis in the human neocortex, either in the healthy brain or after stroke. These results are supported by analyses of neuronal BrdU incorporation and lipofuscin content (Bhardwaj et al, 2006;Huttner et al, 2014). Importantly, the 14 C method has a detection level that limits the possible turnover in the human neocortex to an extremely small or short-lived subpopulation of neurons.…”

Section: Neocortexmentioning

confidence: 76%

“…Importantly, the 14 C method has a detection level that limits the possible turnover in the human neocortex to an extremely small or short-lived subpopulation of neurons. When combined with other methods it can have an even higher sensitivity, being able to detect newborn neurons at densities as low as 1:1000 neurons (Huttner et al, 2014;Bhardwaj et al, 2006). As noted for the striatum, these results do not completely rule out neuronal turnover in the neocortex.…”

Section: Neocortexmentioning

confidence: 82%

“…Although isolated newborn neurons have been reported in the rodent neocortex injured by stroke or selective neuronal loss (Ohira et al, 2010;Li et al, 2008;Jiang et al, 2001;Magavi et al, 2000;Chen et al, 2004;Brill et al, 2009), other groups have found no such neurons (Arvidsson et al, 2002;Parent et al, 2002;Diaz et al, 2013;Huttner et al, 2014). Studies that analyzed the incorporation of 14 C in the DNA of dividing cells observed no neurogenesis in the human neocortex, either in the healthy brain or after stroke.…”

Section: Neocortexmentioning

confidence: 99%

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Stars from the darkest night: unlocking the neurogenic potential of astrocytes in different brain regions

Magnusson

Frisén

2016

Development

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In a few regions of the adult brain, specialized astrocytes act as neural stem cells capable of sustaining life-long neurogenesis. In other, typically non-neurogenic regions, some astrocytes have an intrinsic capacity to produce neurons when provoked by particular conditions but do not use this ability to replace neurons completely after injury or disease. Why do astrocytes display regional differences and why do they not use their neurogenic capacity for brain repair to a greater extent? In this Review, we discuss the neurogenic potential of astrocytes in different brain regions and ask what stimulates this potential in some regions but not in others. We discuss the transcriptional networks and environmental cues that govern cell identity, and consider how the activation of neurogenic properties in astrocytes can be understood as the de-repression of a latent neurogenic transcriptional program.

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“…However, without any further pharmacological mobilization, the vast majority of newly generated neuroblasts in ischemic stroke models die by the time they have reached the peri-infarct area [36] . Moreover, neurogenesis after stroke seems to play even less a role in humans than it does in rodent models [94] . Those recent findings highlight the…”

Section: Imaging Endogenous Neural Stem Cells In Vivomentioning

confidence: 99%

In vivoimaging of endogenous neural stem cells in the adult brain

Rueger

Schroeter

2015

WJSC

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The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those eNSCs can be mobilized in vivo , enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor eNSC activation in a longitudinal and intraindividual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography (PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3'-deoxy-3'-[18 F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs, and will help to facilitate a translation into the clinical setting.

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The age and genomic integrity of neurons after cortical stroke in humans

Abstract: The age and genomic integrity of neurons after cortical stroke in humans. Nature neurosciencehttp://dx

Cited by 111 publications

References 26 publications

Emergent properties of neural repair: elemental biology to therapeutic concepts

Emergent properties of neural repair: elemental biology to therapeutic concepts

Stars from the darkest night: unlocking the neurogenic potential of astrocytes in different brain regions

In vivoimaging of endogenous neural stem cells in the adult brain

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