Longitudinal <i>in vivo</i> Imaging Reveals Balanced and Branch-Specific Remodeling of Mature Cortical Pyramidal Dendritic Arbors after Stroke

Brown, Craig E.; Boyd, Jeffrey E.; Murphy, Timothy H.

doi:10.1038/jcbfm.2009.241

Cited by 110 publications

(93 citation statements)

References 42 publications

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“…However, our findings differ significantly from a recent in vivo two-photon microscopy study that examined the length and branching of pyramidal dendrites in peri-infarct cortex (Brown et al, 2010). The authors followed cortical pyramidal cells for up to 6 weeks after a photo-thrombotic stroke, which produces relatively tiny and well-circumscribed infarcts.…”

Section: Discussioncontrasting

confidence: 56%

“…This was somewhat surprising as we expected that dendrites closer to the infarct edge, because they were exposed to more ischemia, might suffer more retractions, as reported previously (Brown et al, 2010). The difference may reside in the fact that we sampled dendrites significantly farther away from the infarct edge.…”

Section: Discussionmentioning

confidence: 56%

“…In this regard, a recent longitudinal in vivo imaging study found evidence for balanced elongation-retraction of pyramidal dendrites as a mechanism of large-scale dendritic plasticity in peri-infarct cortex after a small photo-thrombotic stroke (Brown et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Absence of Large-Scale Dendritic Plasticity of Layer 5 Pyramidal Neurons in Peri-Infarct Cortex

Mostany

Portera‐Cailliau²

2011

J. Neurosci.

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When stroke or traumatic brain injury lead to cortical damage, how do surviving neurons rewire the brain to restore lost functionalities? Several Golgi studies have argued for de novo growth and branching of dendrites of pyramidal neurons in the spared hemisphere, but the results could not always be replicated. Functional brain imaging studies in humans and rodents suggest that significant neuronal plasticity occurs in areas surrounding the cortical lesion, but whether dendritic rearrangements occur there has been less well studied, especially after stroke. We used in vivo two-photon microscopy in adult mice expressing green fluorescent protein to monitor longitudinally the length and branch complexity of entire apical dendritic arbors from layer 5 pyramidal neurons distributed over a large peri-infarct cortex region after middle cerebral artery occlusion. We find no evidence of growth of dendrites or addition of new branches to their arbors over a period of 3 months after stroke. Instead, we observed a two-step pruning process: an initial decrease in dendritic length, followed by a loss of dendritic branches. Importantly, the shortening of branch tips reflected a general shrinkage in the dendritic apical tree, suggesting that mechanical forces attributable to the involution of the infarct contributed to the changes in dendritic length. These results help resolve a long-standing debate regarding the role of large-scale dendritic plasticity of pyramidal neurons in functional recovery after cortical injury.

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 56%

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Absence of Large-Scale Dendritic Plasticity of Layer 5 Pyramidal Neurons in Peri-Infarct Cortex

Mostany

Portera‐Cailliau²

2011

J. Neurosci.

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“…This can be seen also as supernumerary axons exiting the neuronal cell body [66]. The actual branches of dendrites also remodel after stroke, with retraction and growth that is maximal 2 weeks after the infarct and occurs most prominently within 200 μm of the infarct core [67]. Stroke also induces new axonal connections from neurons in peri-infarct cortex, which are initiated in the first week after stroke and are reliably present 1 month after stroke [39,68,69], particularly in the superficial cortical layers.…”

Section: Radial Stroke: Tissue Reorganizationmentioning

confidence: 99%

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Carmichael

2016

Neurotherapeutics

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Stroke not only causes initial cell death, but also a limited process of repair and recovery. As an overall biological process, stroke has been most often considered from the perspective of early phases of ischemia, how these inter-relate and lead to expansion of the infarct. However, just as the biology of later stages of stroke becomes better understood, the clinical realities of stroke indicate that it is now more a chronic disease than an acute killer. As an overall biological process, it is now more important to understand how early cell death leads to the later, limited recovery so as develop an integrative view of acute to chronic stroke. This progression from death to repair involves sequential stages of primary cell death, secondary injury events, reactive tissue progenitor responses, and formation of new neuronal circuits. This progression is radial: from the tissue that suffers the infarct secondary injury signals, including free radicals and inflammatory cytokines, radiate out from the stroke core to trigger later regenerative events. Injury and repair processes occur not just in the local stroke site, but are also triggered in the connected networks of neurons that had existed in the stroke center: damage signals are relayed throughout a brain network. From these relayed, distributed damage signals, reactive astrocytosis, inflammatory processes, and the formation of new connections occur in distant brain areas. In short, emerging data in stroke cell death studies and the development of the field of stroke neural repair now indicate a continuum in time and in space of progressive events that can be considered as the 3 Rs of stroke biology: radial, relayed, and regenerative.

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“…Whereas extensive literature has shown that rehabilitation can increase the numbers of dendritic spines and dendritic complexity in the cortical hemisphere opposite a brain lesion (10)(11)(12)(13) and is associated with improved skill in the limb unaffected by the lesion, effects of rehabilitation on neuronal structure in perilesioned cortex have not been described. Indeed, some studies suggest either stability or early loss of dendritic structure in perilesion cortex (14)(15)(16). However, knowing whether rehabilitation can drive adaptive brain plasticity could be essential in improving outcomes of numerous CNS disorders acquired in adulthood, including stroke, traumatic brain injury, and spinal cord injury.…”

mentioning

confidence: 99%

Rehabilitation drives enhancement of neuronal structure in functionally relevant neuronal subsets

Wang

Conner

Nagahara

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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We determined whether rehabilitation after cortical injury also drives dynamic dendritic and spine changes in functionally distinct subsets of neurons, resulting in functional recovery. Moreover, given known requirements for cholinergic systems in mediating complex forms of cortical plasticity, including skilled motor learning, we hypothesized that cholinergic systems are essential mediators of neuronal structural and functional plasticity associated with motor rehabilitation. Adult rats learned a skilled forelimb grasping task and then, underwent destructive lesions of the caudal forelimb region of the motor cortex, resulting in nearly complete loss of grasping ability. Subsequent intensive rehabilitation significantly enhanced both dendritic architecture and spine number in the adjoining rostral forelimb area compared with that in the lesioned animals that were not rehabilitated. Cholinergic ablation markedly attenuated rehabilitation-induced recovery in both neuronal structure and motor function. Thus, rehabilitation focused on an affected limb robustly drives structural compensation in perilesion cortex, enabling functional recovery.cell filling | corticospinal neurons | cholinergic | morphology | plasticity S tudies over the past decade have indicated that the adult brain is structurally dynamic (1-3). Indeed, dendritic spines dynamically turn over in the adult brain (3, 4), and learning of novel tasks is associated with further increases in spine turnover (4). Moreover, total and stable increases in spine number together with enhanced dendritic complexity can be detected when analyses are focused specifically on neuronal subpopulations that are functionally related to a newly learned motor skill (5). For example, we recently reported that cortical layer V pyramidal neurons, which project to spinal segment C8 and are specifically engaged when learning a skilled forelimb grasping task, elaborate a 22% increase in apical dendritic spines and exhibit significant increases in dendritic branching and total dendritic length (5); an adjoining control population of cortical layer V pyramidal neurons that project to C4, which are not specifically shaped by the skilled motor task, exhibits no change in spines or dendritic complexity when the same task is learned (5). The detection of stable structural increases in neurons engaged by skilled motor learning in contrast to a lack of change in adjacent neurons that are not engaged by learning advances our understanding of mechanisms underlying experience-dependent cortical plasticity.Damage to the adult CNS also generates adaptive brain plasticity. For example, focal cortical lesions evoke cortical map plasticity (6, 7), extension of new axonal connections (7,8), and neurogenesis (9). A very important and unresolved question in the neural plasticity and injury fields is whether rehabilitation-that is, specific retraining of injured neural circuits-can drive, alter, or enhance neural plasticity subsequent to brain lesions. Whereas extensive literature has shown that rehab...

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Longitudinal in vivo Imaging Reveals Balanced and Branch-Specific Remodeling of Mature Cortical Pyramidal Dendritic Arbors after Stroke

Cited by 110 publications

References 42 publications

Absence of Large-Scale Dendritic Plasticity of Layer 5 Pyramidal Neurons in Peri-Infarct Cortex

Absence of Large-Scale Dendritic Plasticity of Layer 5 Pyramidal Neurons in Peri-Infarct Cortex

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Rehabilitation drives enhancement of neuronal structure in functionally relevant neuronal subsets

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