CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury


M.T. Joy, E. Ben Assayag, D. Shabashov-Stone, S. Liraz-Zaltsman, J. Mazzitelli, M. Arenas, N. Abduljawad, E. Kliper, A.D. Korczyn, N.S. Thareja, E.L. Kesner, M. Zhou, S. Huang, T.K. Silva, N. Katz, N.M. Bornstein, A.J. Silva, E. Shohami, and S.T. Carmichael. 2019. “CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury.” Cell, 176, 5, Pp. 1143-1157.e13.


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. © 2019 Elsevier Inc. Genetic and small molecule-based perturbation of CCR5 promotes functional recovery from stroke and traumatic brain injury. © 2019 Elsevier Inc.


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Last updated on 02/09/2021