학술논문
CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury.
Document Type
article
Author
Joy, Mary T; Ben Assayag, Einor; Shabashov-Stone, Dalia; Liraz-Zaltsman, Sigal; Mazzitelli, Jose; Arenas, Marcela; Abduljawad, Nora; Kliper, Efrat; Korczyn, Amos D; Thareja, Nikita S; Kesner, Efrat L; Zhou, Miou; Huang, Shan; Silva, Tawnie K; Katz, Noomi; Bornstein, Natan M; Silva, Alcino J; Shohami, Esther; Carmichael, S Thomas
Source
Cell. 176(5)
Subject
Language
Abstract
We tested a newly described molecular memory system, CCR5 signaling, for its role in recovery after stroke and traumatic brain injury (TBI). CCR5 is uniquely expressed in cortical neurons after stroke. Post-stroke neuronal knockdown of CCR5 in pre-motor cortex leads to early recovery of motor control. Recovery is associated with preservation of dendritic spines, new patterns of cortical projections to contralateral pre-motor cortex, and upregulation of CREB and DLK signaling. Administration of a clinically utilized FDA-approved CCR5 antagonist, devised for HIV treatment, produces similar effects on motor recovery post stroke and cognitive decline post TBI. Finally, in a large clinical cohort of stroke patients, carriers for a naturally occurring loss-of-function mutation in CCR5 (CCR5-Δ32) exhibited greater recovery of neurological impairments and cognitive function. In summary, CCR5 is a translational target for neural repair in stroke and TBI and the first reported gene associated with enhanced recovery in human stroke.