| Literature DB >> 30794775 |
Mary T Joy1, Einor Ben Assayag2, Dalia Shabashov-Stone3, Sigal Liraz-Zaltsman4, Jose Mazzitelli1, Marcela Arenas1, Nora Abduljawad1, Efrat Kliper5, Amos D Korczyn6, Nikita S Thareja1, Efrat L Kesner3, Miou Zhou7, Shan Huang7, Tawnie K Silva7, Noomi Katz8, Natan M Bornstein2, Alcino J Silva7, Esther Shohami3, S Thomas Carmichael9.
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.Entities:
Keywords: MOCA; NIHSS; astrocyte; axon; axonal sprouting; dendritic spine; microglia; motor; premotor
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Year: 2019 PMID： 30794775 PMCID： PMC7259116 DOI： 10.1016/j.cell.2019.01.044
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850