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

Mary T. Joy; Einor Ben Assayag; Dalia Shabashov-Stone; Sigal Liraz-Zaltsman; Jose 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

doi:10.1016/j.cell.2019.01.044

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

Mary T. Joy, Einor Ben Assayag, Dalia Shabashov-Stone, Sigal Liraz-Zaltsman, Jose 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^*

^*Corresponding author for this work

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

264 Scopus citations

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.

Original language	English
Pages (from-to)	1143-1157.e13
Journal	Cell
Volume	176
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2019.01.044
State	Published - 21 Feb 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

MOCA
NIHSS
astrocyte
axon
axonal sprouting
dendritic spine
microglia
motor
premotor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2019.01.044

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Joy, M. T., Ben Assayag, E., Shabashov-Stone, D., Liraz-Zaltsman, S., Mazzitelli, J., Arenas, M., Abduljawad, N., Kliper, E., Korczyn, A. D., Thareja, N. S., Kesner, E. L., Zhou, M., Huang, S., Silva, T. K., Katz, N., Bornstein, N. M., Silva, A. J., Shohami, E., & Carmichael, S. T. (2019). CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury. Cell, 176(5), 1143-1157.e13. https://doi.org/10.1016/j.cell.2019.01.044

@article{ae144a2de9fc44c1acef2849bc999759,

title = "CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury",

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.",

keywords = "MOCA, NIHSS, astrocyte, axon, axonal sprouting, dendritic spine, microglia, motor, premotor",

author = "Joy, {Mary T.} and {Ben Assayag}, Einor and Dalia Shabashov-Stone and Sigal Liraz-Zaltsman and Jose Mazzitelli and Marcela Arenas and Nora Abduljawad and Efrat Kliper and Korczyn, {Amos D.} and Thareja, {Nikita S.} and Kesner, {Efrat L.} and Miou Zhou and Shan Huang and Silva, {Tawnie K.} and Noomi Katz and Bornstein, {Natan M.} and Silva, {Alcino J.} and Esther Shohami and Carmichael, {S. Thomas}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = feb,

day = "21",

doi = "10.1016/j.cell.2019.01.044",

language = "אנגלית",

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Joy, 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 & Carmichael, ST 2019, 'CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury', Cell, vol. 176, no. 5, pp. 1143-1157.e13. https://doi.org/10.1016/j.cell.2019.01.044

TY - JOUR

T1 - CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury

AU - Joy, Mary T.

AU - Ben Assayag, Einor

AU - Shabashov-Stone, Dalia

AU - Liraz-Zaltsman, Sigal

AU - Mazzitelli, Jose

AU - Arenas, Marcela

AU - Abduljawad, Nora

AU - Kliper, Efrat

AU - Korczyn, Amos D.

AU - Thareja, Nikita S.

AU - Kesner, Efrat L.

AU - Zhou, Miou

AU - Huang, Shan

AU - Silva, Tawnie K.

AU - Katz, Noomi

AU - Bornstein, Natan M.

AU - Silva, Alcino J.

AU - Shohami, Esther

AU - Carmichael, S. Thomas

PY - 2019/2/21

Y1 - 2019/2/21

N2 - 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.

AB - 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.

KW - MOCA

KW - NIHSS

KW - astrocyte

KW - axon

KW - axonal sprouting

KW - dendritic spine

KW - microglia

KW - motor

KW - premotor

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C2 - 30794775

AN - SCOPUS:85061160423

SN - 0092-8674

VL - 176

SP - 1143-1157.e13

JO - Cell

JF - Cell

IS - 5

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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