CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury
Mary T Joy, Einor Ben Assayag, Dalia Shabashov-Stone, Sigal Liraz-Zaltsman, Jose Mazzitelli, Marcela Arenas, Nora Abduljawad, Efrat Kliper, Amos D Korczyn, Nikita S Thareja, Efrat L Kesner, Miou Zhou, Shan Huang, Tawnie K Silva, Noomi Katz, Natan M Bornstein, Alcino J Silva, Esther Shohami, S Thomas Carmichael, Mary T Joy, Einor Ben Assayag, Dalia Shabashov-Stone, Sigal Liraz-Zaltsman, Jose Mazzitelli, Marcela Arenas, Nora Abduljawad, Efrat Kliper, Amos D Korczyn, Nikita S Thareja, Efrat L Kesner, Miou Zhou, Shan Huang, Tawnie K Silva, Noomi Katz, Natan M Bornstein, Alcino J Silva, Esther Shohami, S Thomas Carmichael
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.
Keywords: MOCA; NIHSS; astrocyte; axon; axonal sprouting; dendritic spine; microglia; motor; premotor.
Conflict of interest statement
DECLARATION OF INTERESTS
The authors declare no competing interests.
Copyright © 2019 Elsevier Inc. All rights reserved.
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Source: PubMed