000219266 001__ 219266
000219266 005__ 20190317000500.0
000219266 0247_ $$2doi$$a10.1038/nature17623
000219266 022__ $$a0028-0836
000219266 02470 $$2ISI$$a000374415100031
000219266 037__ $$aARTICLE
000219266 245__ $$aAstrocyte scar formation aids central nervous system axon regeneration
000219266 269__ $$a2016
000219266 260__ $$aLondon$$bNature Publishing Group$$c2016
000219266 300__ $$a20
000219266 336__ $$aJournal Articles
000219266 520__ $$aTransected axons fail to regrow in the mature central nervous system. Astrocytic 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 ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By 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 astrocytic 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 the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration.
000219266 700__ $$aAnderson, Mark A.$$uUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
000219266 700__ $$aBurda, Joshua E.$$uUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
000219266 700__ $$aRen, Yilong$$uUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
000219266 700__ $$aAo, Yan$$uUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
000219266 700__ $$aO'Shea, Timothy M.$$uUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
000219266 700__ $$aKawaguchi, Riki$$uUniv Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA
000219266 700__ $$aCoppola, Giovanni$$uUniv Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA
000219266 700__ $$aKhakh, Baljit S.$$uUniv Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA
000219266 700__ $$aDeming, Timothy J.$$uUniv Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA
000219266 700__ $$aSofroniew, Michael V.$$uUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
000219266 773__ $$j532$$k7598$$q195-+$$tNature
000219266 8564_ $$s35532776$$uhttps://infoscience.epfl.ch/record/219266/files/Nature2016.pdf$$yn/a$$zn/a
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000219266 937__ $$aEPFL-ARTICLE-219266
000219266 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000219266 980__ $$aARTICLE