Reactivation of Dormant Relay Pathways in Injured Spinal Cord by KCC2 Manipulations.

ABSTRACT: Many human spinal cord injuries are anatomically incomplete but exhibit complete paralysis. It is unknown why spared axons fail to mediate functional recovery in these cases. To investigate this, we undertook a small-molecule screen in mice with staggered bilateral hemisections in which the lumbar spinal cord is deprived of all direct brain-derived innervation, but dormant relay circuits remain. We discovered that a KCC2 agonist restored stepping ability, which could be mimicked by selective expression of KCC2, or hyperpolarizing DREADDs, in the inhibitory interneurons between and around the staggered spinal lesions. Mechanistically, these treatments transformed this injury-induced dysfunctional spinal circuit to a functional state, facilitating the relay of brain-derived commands toward t

SUBMITTER: Chen B 

PROVIDER: S-EPMC6063786 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature