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2016 ; 11
(9
): 1368-1371
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Regeneration-associated macrophages: a novel approach to boost intrinsic
regenerative capacity for axon regeneration
#MMPMID27857723
Kwon MJ
; Yoon HJ
; Kim BG
Neural Regen Res
2016[Sep]; 11
(9
): 1368-1371
PMID27857723
show ga
Axons in central nervous system (CNS) do not regenerate spontaneously after
injuries such as stroke and traumatic spinal cord injury. Both intrinsic and
extrinsic factors are responsible for the regeneration failure. Although
intensive research efforts have been invested on extrinsic regeneration
inhibitors, the extent to which glial inhibitors contribute to the regeneration
failure in vivo still remains elusive. Recent experimental evidence has rekindled
interests in intrinsic factors for the regulation of regeneration capacity in
adult mammals. In this review, we propose that activating macrophages with
pro-regenerative molecular signatures could be a novel approach for boosting
intrinsic regenerative capacity of CNS neurons. Using a conditioning injury model
in which regeneration of central branches of dorsal root ganglia sensory neurons
is enhanced by a preceding injury to the peripheral branches, we have
demonstrated that perineuronal macrophages surrounding dorsal root ganglia
neurons are critically involved in the maintenance of enhanced regeneration
capacity. Neuron-derived chemokine (C-C motif) ligand 2 (CCL2) seems to mediate
neuron-macrophage interactions conveying injury signals to perineuronal
macrophages taking on a soley pro-regenerative phenotype, which we designate as
regeneration-associated macrophages (RAMs). Manipulation of the CCL2 signaling
could boost regeneration potential mimicking the conditioning injury, suggesting
that the chemokine-mediated RAM activation could be utilized as a regenerative
therapeutic strategy for CNS injuries.