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

Mary T. Joy | Zendy; Einor Ben Assayag | Zendy; Dalia Shabashov-Stone | Zendy; Sigal LirazZaltsman | Zendy; Jose A. Mazzitelli | Zendy; Marcela Arenas | Zendy; Nora Abduljawad | Zendy; Efrat Kliper | Zendy; Amos D. Korczyn | Zendy; Nikita S. Thareja | Zendy; Efrat L. Kesner | Zendy; Miou Zhou | Zendy; Shan Huang | Zendy; Tawnie K. Silva | Zendy; Noomi Katz | Zendy; Natan M. Bornstein | Zendy; Alcino J. Silva | Zendy; Esther Shohami | Zendy; S. Thomas Carmichael | Zendy

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

Author(s) -

Mary T. Joy,

Einor Ben Assayag,

Dalia Shabashov-Stone,

Sigal LirazZaltsman,

Jose A. 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

Publication year - 2019

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2019.01.044

Subject(s) - stroke (engine) , stroke recovery , traumatic brain injury , neuroscience , dendritic spine , biology , motor cortex , ccr5 receptor antagonist , cortex (anatomy) , medicine , receptor , rehabilitation , psychiatry , stimulation , engineering , biochemistry , chemokine , chemokine receptor , mechanical engineering , hippocampal formation

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.

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