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Abstract

The precise wiring of the adult mammalian CNS originates during a period of stunning growth, guidance and plasticity that occurs during and shortly after development. When injured in adults, this intricate system fails to regenerate. Even when the obstacles to regeneration are cleared, growing adult CNS fibres usually remain misdirected and fail to reform functional connections. Here, we attempt to fill an important niche related to the topics of nervous system development and regeneration. We specifically contrast the difficulties faced by growing fibres within the adult context to the precise circuit-forming capabilities of developing fibres. In addition to focusing on methods to stimulate growth in the adult, we also expand on approaches to recapitulate development itself.

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Most cited references 205

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Neuronal replacement from endogenous precursors in the adult brain after stroke.

Andreas Arvidsson, Tove Collin, Deniz Kirik … (2002)

In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans.

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Transient and persistent dendritic spines in the neocortex in vivo.

Anthony Holtmaat, Joshua T. Trachtenberg, Linda Wilbrecht … (2005)

Dendritic spines were imaged over days to months in the apical tufts of neocortical pyramidal neurons (layers 5 and 2/3) in vivo. A fraction of thin spines appeared and disappeared over a few days, while most thick spines persisted for months. In the somatosensory cortex, from postnatal day (PND) 16 to PND 25 spine retractions exceeded additions, resulting in a net loss of spines. The fraction of persistent spines (lifetime > or = 8 days) grew gradually during development and into adulthood (PND 16-25, 35%; PND 35-80, 54%; PND 80-120, 66%; PND 175-225, 73%), providing evidence that synaptic circuits continue to stabilize even in the adult brain, long after the closure of known critical periods. In 6-month-old mice, spines turn over more slowly in visual compared to somatosensory cortex, possibly reflecting differences in the capacity for experience-dependent plasticity in these brain regions.

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Molecular mechanisms of axon guidance.

Barry Dickson (2002)

Axons are guided along specific pathways by attractive and repulsive cues in the extracellular environment. Genetic and biochemical studies have led to the identification of highly conserved families of guidance molecules, including netrins, Slits, semaphorins, and ephrins. Guidance cues steer axons by regulating cytoskeletal dynamics in the growth cone through signaling pathways that are still only poorly understood. Elaborate regulatory mechanisms ensure that a given cue elicits the right response from the right axons at the right time but is otherwise ignored. With such regulatory mechanisms in place, a relatively small number of guidance factors can be used to generate intricate patterns of neuronal wiring.

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PubMed ID:: 16858389

PMC ID:: 2288666

DOI:: 10.1038/nrn1957

ScienceOpen disciplines: Chemistry

Keywords: Animals,Axons,physiology,Feedback, Physiological,Humans,Nerve Regeneration,Neuronal Plasticity,Recovery of Function,Spinal Cord Injuries,metabolism,physiopathology

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ScienceOpen disciplines: Chemistry

Keywords: Animals, Axons, physiology, Feedback, Physiological, Humans, Nerve Regeneration, Neuronal Plasticity, Recovery of Function, Spinal Cord Injuries, metabolism, physiopathology

Can regenerating axons recapitulate developmental guidance during recovery from spinal cord injury?

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Photoluminescent Nanomaterials

Most cited references 205

Neuronal replacement from endogenous precursors in the adult brain after stroke.

Transient and persistent dendritic spines in the neocortex in vivo.

Molecular mechanisms of axon guidance.

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