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

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

310 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

Funding

Funders	Funder number
American Heart Foundation	16POST27710039
Alzheimer's Association	16-442861
American Federation for Aging Research	RAG11482
American Hungarian Foundation
Stanford University
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
University of California, Los Angeles
United States-Israel Binational Science Foundation	2011344

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

MOCA
NIHSS
astrocyte
axon
axonal sprouting
dendritic spine
microglia
motor
premotor

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10.1016/j.cell.2019.01.044

Cite this

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{a0267fa2ebb949cc94e85adedad637b4,

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",

volume = "176",

pages = "1143--1157.e13",

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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

UR - https://www.scopus.com/pages/publications/85061160423

U2 - 10.1016/j.cell.2019.01.044

DO - 10.1016/j.cell.2019.01.044

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

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

Funding

UN SDGs

Keywords

Access to Document

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