Posts Tagged brain repair

[TED Talk] The brain may be able to repair itself — with help | Jocelyne Bloch – YouTube

Through treating everything from strokes to car accident traumas, neurosurgeon Jocelyne Bloch knows the brain’s inability to repair itself all too well. But now, she suggests, she and her colleagues may have found the key to neural repair: Doublecortin-positive cells. Similar to stem cells, they are extremely adaptable and, when extracted from a brain, cultured and then re-injected in a lesioned area of the same brain, they can help repair and rebuild it. “With a little help,” Bloch says, “the brain may be able to help itself.”

via The brain may be able to repair itself — with help | Jocelyne Bloch – YouTube

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[Editorial] Adult Neurogenesis: Beyond Rats and Mice – Neuroscience

Editorial on the Research Topic
Adult Neurogenesis: Beyond Rats and Mice

Most biological tissues routinely replace old cells with new ones. Unlike other tissues, the nervous system–being the most complex biological device found in nature–uniquely maintains most of its neurons throughout life and replaces relatively few. It preserves hotspots where it generates new neurons from resident stem cells during adulthood in a process known as adult neurogenesis, which varies among different species in its features, dynamics, and regulation. In spite of its widespread prevalence in the animal kingdom, the preponderance of studies conducted on a few laboratory rodent species such as rats and mice limits our understanding of the evolution, regulation, and function of adult neurogenesis. The anatomy, complexity and functions of the brain vary greatly in the animal kingdom: striking differences exist from simple bilaterians to humans, and, to a lesser extent, also among mammals. Therefore, both comparative and focused studies on different species will shed more light on the origin, development, and purpose of adult neurogenesis.

Adult neurogenesis was discovered and described by Joseph Altman and Das in rats (Altman and Das, 1965) and has been investigated in many species such as the zebrafish, frog, songbird, mole, mole-rat, vole, bat, fox, dog, dolphin, elephant, shrew, rabbit, monkey, and human. With the development of genetic manipulation techniques, researchers have focused largely on inbred laboratory rodents. While this provides a strong advantage of restricting genetic variation in the group, it also narrows our perspective on adult neurogenesis as a biological phenomenon (Bolker, 2017). Moreover, the rapid development of genetic tools has made Mus musculus the species of choice in studying adult neurogenesis. Yet, many unsolved issues and open questions cannot be resolved without the contribution of comparative studies spanning through widely different species. Such issues involve: how did adult neurogenesis evolve, whether our survival depend on adult neurogenesis, what is the link between adult neurogenesis and brain complexity, how do adult neurogenesis and animal behavior influence each other, how does adult neurogenesis contribute to brain plasticity, cognition and, possibly, repair, and how do experimental conditions affect adult neurogenesis.

Studying unconventional species will give us insights into the evolution and function of the brain, strengthening our understanding of the cellular basis of cognition and behavior, thus helping adult neurogenesis to find its place in the puzzle. With this Research Topic we, along with contributors from different areas, tried to answer the open questions and to encourage engaging discussions on the comparative and evolutionary aspects of adult neurogenesis. The diversity in adult neurogenesis indeed spans the de-novo formation of the entire adult brain in planaria (Brown and Pearson), neurogenesis in diverse brain areas in fish (Olivera-Pasilio et al.), reptiles (LaDage et al.Lutterschmidt et al.), and birds (Barkan et al.Kosubek-Langer et al.) to animals with restricted neurogenic niches such as invertebrates (Beltz and BentonSimões and Rhiner) and mammals (Taylor et al.Lévy et al.OosthuizenWiget et al.). The striking differences do not only concern the sites of occurrence and relative amounts (Brown and PearsonLévy et al.Olivera-Pasilio et al.Wiget et al.) but also in mechanistic aspects of stem cell biology. Intriguing examples are given by the adult-born neurons generated from the immune system and then traveling to the neurogenic niche via the circulatory system in the crayfish brain (Beltz and BentonSimões and Rhiner), or the heterogeneity of neoblasts, putative stem cells, in flatworms enabling the regeneration of the entire brain (Brown and Pearson). Yet, the main message from the comparative approach to adult neurogenesis is that the relative exclusive focus on laboratory rodents can result in a bias on how we think about this biological process. For instance, promising neuroprotective treatments developed in rodent models can fail in preclinical trials, and animal models with gyrencephalic brains might be necessary to study the behavior of neuroblasts in large white matter tracts (Taylor et al.). The bias is well-illustrated by the article of Faykoo-Martinez et al.: “species-specific adaptations in brain and behavior are paramount to survival and reproduction in diverse ecological niches and it is naive to think adult neurogenesis escaped these evolutionary pressures. A neuroethological approach to the study of adult neurogenesis is essential for a comprehensive understanding of the phenomenon.” Indeed, interactions of adult neurogenesis with neuroethological traits such as migration and mating behavior in snakes (Lutterschmidt et al.), territoriality in lizards (LaDage et al.), sociality and social interactions in mole-rats, birds, and sheep (Barkan et al.Lévy et al.Oosthuizen), or migratory lifestyle in birds (Barkan et al.) are presented here. The complexity of interactions is, to date, more an obstruction than a help in terms of publishability, but as Faykoo-Martinez et al. put it “most of us are guilty of making strong assertions about our data in order to have impact yet this ultimately creates bias in how work is performed, interpreted, and applied.” Such concerns are confirmed by the finding of remarkable reduction of adult neurogenesis in some large-brained, long-living mammals, including humans and dolphins (Sanai et al., 2011Sorrells et al., 2018), as reviewed and discussed in the article by Parolisi et al. More and more comparative data strongly support the view that adult neurogenesis is maintained in evolution only depending on strict relationships with its functional need(s). E.g., olfactory systems, mostly linked to paleocortical-hippocampal structures, were important in early mammalian evolution working as a reference system for spatial navigation for the location of food sources and mates, then replaced/integrated by the expansion of the isocortex as a “multimodal interface” for behavioral navigation based on vision and audition (Aboitiz and Montiel, 2015; see article by Parolisi et al.). The complex evolutionary aspects of adult neurogenesis role(s) and age-related reduction in mammals are addressed in the contribution by Hans-Peter Lipp. The main message of this opinion article is that no simple explanations can be called upon on such topic, a heavily actual conclusion even 30 years after neural stem cell discovery.

Animal models other than laboratory mice are by no means “out-of-reach” for advanced techniques, and the following examples could encourage and facilitate creative thinking in terms of research questions and how to approach them. Lindsey et al. present a thorough step-by-step protocol for visualizing cell proliferation in the whole zebrafish brain in 3 dimension. LaDage et al. used hormonal implants in lizards to study the interaction of testosterone and neurogenesis on territorial behavior. In fish and birds, Neurobiotin or lentivirus can be used to trace and characterize newly born neurons (Kosubek-Langer et al.Olivera-Pasilio et al.), and Brown and Pearson summarize the single-cell genomic data collected in planaria. Ideally, studies in laboratory rodents and non-conventional animal models can support and foster each other. For example, increased neurogenesis in laboratory mice confers stress resilience mediated by the temporal hippocampus (Anacker et al., 2018). Strikingly, wild rodents, naturally exposed to high stress levels, show more neurogenesis in the temporal hippocampus than the commonly used laboratory mouse C57BL/6 (Wiget et al.). Similarly, Reyes-Aguirre and Lamas identified the mechanism why the mouse retina cannot regenerate after damage, much in contrast to what has been reported in fish (Raymond et al., 2006). Finally, by using meta-analyses and a model to compare the neurodevelopmental sequences of different mammals, Charvet and Finlay try to put in a common time frame the envelopes of hippocampal neurogenesis, in order to interpret them in species with highly different lifespan.

In conclusion, with this Research Topic we strongly assert that adult neurogenesis research cannot rely exclusively on laboratory rodents, as each animal model can only cover certain aspects of the various flavors in which neuronal stem cells and their progeny in the postnatal brain can behave. The papers presented here emphasize the value of “… taking a step back and actually placing our results in a much larger, non-biomedical context, …[helping]… to reduce dogmatic thinking and create a framework for discovery” (Faykoo-Martinez et al.). After all, the failure of many clinical trials based on pre-clinical studies carried out on mice (Lindvall and Kokaia, 2010Donegà et al., 2013), do confirm the need for investments in comparative medicine (specifically on brain structural plasticity, see La Rosa and Bonfanti, 2018). A comparative view can indeed foster a more careful interpretation of the final impact of the biological process of neurogenesis in brain functioning and animal behavior.

References

Aboitiz, F., and Montiel, J. F (2015). Olfaction, navigation, and the origin of isocortex. Front. Neurosci. 9:402. doi: 10.3389/fnins.2015.00402

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Altman, J., and Das, G. D (1965). Post-natal origin of microneurones in the rat brain. Nature 207, 953–956. doi: 10.1038/207953a0

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Anacker, C., Luna, V. M., Stevens, G. S., Millette, A., Shores, R., Jimenez, J. C., et al. (2018). Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus. Nature 559, 98–102. doi: 10.1038/s41586-018-0262-4

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Bolker, J. A. (2017). Animal models in translational research: rosetta stone or stumbling block? Bioessays 39, 1–8. doi: 10.1002/bies.201700089

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Donegà, M., Giusto, E., Cossetti, C., and Pluchino, S (2013). “Systemic neural stem cell-based therapeutic interventions for inflammatory CNS disorders,” in Neural Stem Cells: New Perspectives, ed. L. Bonfanti (Rijeka: INTECH), 287–347.

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La Rosa, C., and Bonfanti, L (2018). Brain plasticity in mammals: An example for the role of comparative medicine in the Neurosciences. Front. Vet. Sci.5:274. doi: 10.3389/fvets.2018.00274

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Lindvall, O., and Kokaia, Z (2010). Stem cells in human neurodegenerative disorders-time for clinical translation? J. Clin. Invest. 120, 29–40. doi: 10.1172/JCI40543

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Raymond, P. A., Barthel, L. K., Bernardos, R. L., and Perkowski, J (2006). Molecular characterization of retinal stem cells and their niches in adult zebrafish. BMC Dev. Biol. 6:36. doi: 10.1186/1471-213X-6-36

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Sanai, N., Nguyen, T., Ihrie, R. A., Mirzadeh, Z., Tsai, H.-H., Wong, M., et al. (2011). Corridors of migrating neurons in the human brain and their decline during infancy. Nature 478, 382–386. doi: 10.1038/nature10487

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Sorrells, S. F, Paredes, M. F., Cebrian-Silla, A., Sandoval, K., Qi, D., Kelley, K. W., et al. (2018). Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature 555, 377–381. doi: 10.1038/nature25975

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Keywords: comparative studies, evolution, brain plasticity, adult neurogenesis, brain repair, translation

via Frontiers | Editorial: Adult Neurogenesis: Beyond Rats and Mice | Neuroscience

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[TEDx Talks] A critical window for recovery after stroke – John Krakauer – Johns Hopkins University – YouTube

Δημοσιεύτηκε στις 8 Απρ 2015
Dr. John Krakauer, a Professor of Neurology and Neuroscience at Johns Hopkins University, co-founded the KATA project that combines concepts of neurology and neuroscience with interactive entertainment and motion capture technology to learn how lesions affect motor learning and to aid patients in recovering from brain injury.
Dr. John Krakauer is a Professor of Neurology and Neuroscience, the Director of the Center for the Study of Motor Learning and Brain Repair, and the Director of Brain, Learning, Animation, and Movement Lab (BLAM) at Johns Hopkins. He received his undergraduate and master’s degree from Cambridge University and earned his medical degree from Columbia University College of Physicians and Surgeons, where he was elected to Alpha Omega Alpha Medical Honor Society. His clinical and research expertise is in stroke, ischemic cerebrovascular disease, cerebral aneurysms, arteriovenous malformations, and venous and sinus thrombosis.
He co-founded the KATA project that combines concepts of neurology and neuroscience with interactive entertainment and motion capture technology to learn how lesions affect motor learning and to aid patients in recovering from brain injury.
This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at http://ted.com/tedx

 

via A critical window for recovery after stroke | John Krakauer | TEDxJohnsHopkinsUniversity – YouTube

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[WEB SITE] Study offers novel principle to reroute neurons for brain repair

Restorative neuroscience, the study to identify means to replace damaged neurons and recover permanently lost mental or physical abilities, is a rapidly advancing scientific field considering our progressively aging society. Redirecting immature neurons that reside in specific brain areas towards the sites of brain damage is an appealing strategy for the therapy of acute brain injury or stroke. A collaborative effort between the Center for Brain Research of Medical University of Vienna and the National Brain Research Program of Hungary/Semmelweis University in Budapest revealed that some mature neurons are able to reconfigure their local microenvironment such that it becomes conducive for adult-born immature neurons to extensively migrate. Thus, a molecular principle emerges that can allow researchers to best mobilize resident cellular reserves in the adult brain and guide immature neurons to the sites of brain damage.

The adult brain has limited capacity of self-repair

In the aging Western society, acute brain damage and chronic neurodegenerative conditions (e.g. Alzheimer’s and Parkinson’s diseases) are amongst the most debilitating diseases affecting hundreds of millions of people world-wide. Nerve cells are particularly sensitive to microenvironmental insults and their loss clearly manifests as neurological deficit. Since the innate ability of the adult human brain to regenerate is very poor and confined to its few specialized regions, a key question in present-day neurobiology is how to establish efficient strategies that can replace lost neurons, guide competent cells to the sites of injury and facilitate their functional integration to regain lost functionality. “Cell replacement therapy” thus offers frontline opportunities to design potent therapeutic interventions.

Neurons drive neurons: a new concept integrating brain activity with repair

Only two regions of the postnatal mammalian brain are known to retain their intrinsic potential to allow the generation of new neurons throughout life: the olfactory system decoding smell and the hippocampus acting as a key hub for memory encoding and storage. In humans, the generation of new neurons in the olfactory system rapidly ceases during early childhood. “Which are the processes that disallow this innate regenerative process in the human brain and how can dormant progenitors be reinstated to produce new neurons and guide those towards brain areas that require repair?” is a central yet unresolved question for brain repair strategies.

For neuronal migration, the widely-accepted concept is that support cells called astroglia are of primary importance to promote the movement of adult-born neurons through chemical signals and physical interactions. The new study involving researchers from the Department of Molecular Neurosciences of the Center for Brain Research goes well beyond these known frontiers through the discovery that the migration of new-born neurons requires resident, differentiated nerve cells to “clear their path” by digesting away some of the glue that fills the space between nerve cells. This process is dependent on the activity of resident neurons, thus suggesting the integration of the ancient developmental process of active cell movement with the integrative capacity and activity patterns of the brain. “By realizing that differentiated neurons are critical operators in this process we finally lay our hands on an “on switch” which we can use to produce a molecular landing strip for migrating neuroblasts to home in at areas of critical need” says Alán Alpár, senior author of the study.

Opportunities for restorative neuroscience

Tibor Harkany, Professor of Molecular Neurosciences at the Medical University of Vienna goes one step further “We mapped the entire molecular machinery used by differentiated neurons to make way for their migrating adult-born replacements. This clearly offers a pharmacological concept to reroute neurons in sufficient quantities for neurorepair once damage occurs. Even though distances can be considerably long, we are confident that molecular means exist to tackle these challenges”.

Brain activity defines therapeutic success?

The realization that differentiated neurons hold the key to directional cell migration is of enormous significance since they are wired into the brain circuitry, receive information from not only adjacent but also far-away regions and are activated by these specific connections at precisely given times. Consequently, migration controlled by the newly described specific neuronal subset can be aligned with brain activity, or conversely, with inactivity as evoked by neuronal loss during brain diseases. “To identify the physiological stimuli and stressors, which activate these guide-neurons will herald a new and exciting opportunity for regenerative neuroscience” adds Tomas Hökfelt, Guest Professor at the Center for Brain Research.

Like many other studies at the Department of Molecular Neurosciences, the European Research Council (ERC) and the European Molecular Biology Organisation (EMBO) frontier research programs funded this project. Alán Alpár’s work is supported by the National Brain Research Program of the Hungarian Academy of Sciences.

Source: Study offers novel principle to reroute neurons for brain repair

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