CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury.
Cell
; 176(5): 1143-1157.e13, 2019 02 21.
Article
em En
| MEDLINE
| ID: mdl-30794775
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.
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01-internacional
Base de dados:
MEDLINE
Limite:
Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article