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      Astrocyte scar formation aids CNS axon regeneration

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          Summary

          Transected axons fail to regrow in the mature central nervous system (CNS). Astrocyte scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or deleting chronic astrocyte scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. In striking contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocyte scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth supporting molecules. Our findings show that contrary to prevailing dogma, astrocyte scar formation aids rather than prevents CNS axon regeneration.

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          Author and article information

          Journal
          0410462
          6011
          Nature
          Nature
          Nature
          0028-0836
          1476-4687
          12 January 2017
          30 March 2016
          14 April 2016
          18 January 2017
          : 532
          : 7598
          : 195-200
          Affiliations
          [1 ]Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
          [2 ]Department of Psychiatry and Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095,USA
          [3 ]Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095,USA
          [4 ]Departments of Bioengineering, Chemistry and Biochemistry, University of California Los Angeles, Los Angeles CA 90095, USA
          Author notes
          Correspondence and requests for materials should be addressed to M.V.S ( sofroniew@ 123456mednet.ucla.edu )
          [*]

          contributed equally

          [ˆ]

          Present Address: School of Life Sciences, Swiss Federal Institute of Technology (EPFL), SV BMI UPCourtine, Station 19, CH-1015 Lausanne, Switzerland

          [#]

          Present Address: Department of Spine Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China

          Article
          PMC5243141 PMC5243141 5243141 nihpa842342
          10.1038/nature17623
          5243141
          27027288
          918e2d51-e890-46a5-8551-181d6f54a081

          Reprints and permissions information is available at www.nature.com/reprints

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