CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury
| Autor: | Miou Zhou, Nora Abduljawad, Esther Shohami, Sigal Liraz-Zaltsman, Efrat L. Kesner, Einor Ben Assayag, Shan Huang, S. Thomas Carmichael, Jose A. Mazzitelli, Alcino J. Silva, Marcela Arenas, Efrat Kliper, Natan M. Bornstein, Tawnie K. Silva, Nikita S. Thareja, Dalia Shabashov-Stone, Noomi Katz, Mary T. Joy, Amos D. Korczyn |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Dendritic spine Receptors CCR5 Traumatic brain injury Dendritic Spines Biology CREB General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cortex (anatomy) Brain Injuries Traumatic medicine Animals Humans Cognitive decline Cyclic AMP Response Element-Binding Protein Stroke 030304 developmental biology Aged Aged 80 and over Neurons 0303 health sciences Neuronal Plasticity Motor Cortex Stroke Rehabilitation virus diseases Motor control Middle Aged medicine.disease Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure biology.protein Female Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cell. 176(5) |
| ISSN: | 1097-4172 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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