Growth-associated gene expression after stroke: evidence for a growth-promoting region in peri-infarct cortex

Carmichael, S. Thomas; Archibeque, Ivonne; Luke, Linslee M.; Nolan, Tim; Momiy, Janneth; Li, Songlin

doi:10.1016/j.expneurol.2005.01.004

Cited by 375 publications

(376 citation statements)

References 86 publications

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“…In the cortex adjacent to the stroke core, neurons lose their perineuronal net, show altered intracortical inhibition, and become growth factor dependent 5, 12, 113, 114. These are hallmarks of neurons in the critical period of neuronal development, when cortex is uniquely plastic to environmental alterations in physiology and structure 115.…”

Section: Regeneration Does Not Recapitulate Developmentmentioning

confidence: 99%

Emergent properties of neural repair: elemental biology to therapeutic concepts

Carmichael

2016

Annals of Neurology

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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: Regeneration Does Not Recapitulate Developmentmentioning

confidence: 99%

Emergent properties of neural repair: elemental biology to therapeutic concepts

Carmichael

2016

Annals of Neurology

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118

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“…The TGF-β family member growth differentiation factor 10 (GDF10) is induced in peri-infarct cortex after stroke and is a potent stimulant for axonal sprouting and functional recovery [36]. Activation of astrocytes in peri-infarct cortex, in part through inflammatory cytokines, induces molecules that block axonal sprouting, such as chondroitin sulfate proteoglycans or ephrin-A5 [37][38][39]. Thus, peri-infarct inflammatory signals control both the induction of axonal sprouting and the induction of axonal growth inhibitors that block axonal sprouting.…”

Section: Radial Stroke: Triggers For Neural Repairmentioning

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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“…Increased neurotrophic factor expression is thought to promote dendritic and axonal sprouting in residual cortical tissue in order to support compensatory recovery. Growth-promoting genes are also upregulated in periinfarct cortex after stroke (Carmichael et al, 2005). The highly regulated temporal expression of growth-promoting and growth-inhibiting genes reduces peri-neuronal nets and increases peri-infarct axonal sprouting.…”

Section: Molecular Changesmentioning

confidence: 99%