Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury.

Dias DO, Kim H, Holl D, Werne Solnestam B, Lundeberg J, Carlén M, Göritz C, Frisén J

Cell 173 (1) 153-165.e22 [2018-03-22; online 2018-03-01]

CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report that inhibiting the generation of progeny by a subclass of pericytes led to decreased fibrosis and extracellular matrix deposition after spinal cord injury in mice. Regeneration of raphespinal and corticospinal tract axons was enhanced and sensorimotor function recovery improved following spinal cord injury in animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate that regenerated corticospinal tract axons integrated into the local spinal cord circuitry below the lesion site. The number of regenerated axons correlated with improved sensorimotor function recovery. In conclusion, attenuation of pericyte-derived fibrosis represents a promising therapeutic approach to facilitate recovery following CNS injury.

Bioinformatics Compute and Storage [Service]

NGI Stockholm (Genomics Applications) [Service]

NGI Stockholm (Genomics Production) [Service]

QC bibliography QC xrefs

PubMed 29502968

DOI 10.1016/j.cell.2018.02.004

Crossref 10.1016/j.cell.2018.02.004

S0092-8674(18)30148-X

pmc PMC5871719

GEO GSE93976 [In vivo analysis of injury sites presenting full or attenuated pericyte-derived scarring after spinal cord injury (SCI)]