Title | CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Joy MT, Ben Assayag E, Shabashov-Stone D, Liraz-Zaltsman S, Mazzitelli J, Arenas M, Abduljawad N, Kliper E, Korczyn AD, Thareja NS, Kesner EL, Zhou M, Huang S, Silva TK, Katz N, Bornstein NM, Silva AJ, Shohami E, S Carmichael T |
Journal | Cell |
Volume | 176 |
Issue | 5 |
Pagination | 1143-1157.e13 |
Date Published | 2019 Feb 21 |
ISSN | 1097-4172 |
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. |
DOI | 10.1016/j.cell.2019.01.044 |
Alternate Journal | Cell |
PubMed ID | 30794775 |