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. 2022 Nov 4;38(12):1569–1587. doi: 10.1007/s12264-022-00959-x

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — The potential circuit basis and molecular mechanism for implementation of ipsilateral motor control and the cellular mechanism of axon regeneration. A Schematic organization of ipsilateral motor pathways. The mechanism of ipsilateral motor control may include the following possibilities: 1. The contralesional cortex controls the remaining CST in the impaired hemisphere by callosal fiber enhancement; 2. Synaptic connections between the contralesional cortex and the ipsilesional subcortical areas are increased; 3. The crossed CST originating from the contralesional cortex sprouts across the midline to the damage-denervated side of the spinal cord; 4. The number and activity of uncrossed CST fibers from the contralesional cortex to the affected spinal cord are increased. B Cartoon showing the difference between CST axonal sprouting and regeneration in the spinal cord. Axon growth including axon sprouting and axon regeneration. The sprouting refers to axon regrowth from intact neurons on the unaffected side, and regenerating axons arise from the cut ends of the transected axon of injured neurons. C Factors that enhance axon growth are shown in the yellow box, while factors that inhibit axon growth are shown in the blue box. Note that both CST regrowth (green) and spared CST axons (blue) aim to re-innervate the spinal cord of the affected side. D, There are two forms of axon regeneration in spinal cord injury, one in which regenerating axons cross through the glial scars, and one in which regenerating axons bypass the injury site. E Cellular mechanisms that facilitate the passage of regenerating axons across the astroglial scar. The neonatal microglia secrete fibronectin and their binding proteins to establish a bridge to the extracellular matrix and express various peptidase inhibitors to promote CST regrowth to pass through the injury site. Nerve/glial antigen 2 positive (NG2⁺) cells increase scar formation by secreting pro-inflammatory factors that impede the passage of regenerating axons through glial scars.