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Department of Anesthesiology

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

TitleCCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury.
Publication TypeJournal Article
Year of Publication2019
AuthorsJoy 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
JournalCell
Volume176
Issue5
Pagination1143-1157.e13
Date Published2019 Feb 21
ISSN1097-4172
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.

DOI10.1016/j.cell.2019.01.044
Alternate JournalCell
PubMed ID30794775