Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation

Jun Nagai; Yoshiteru Kitamura; Kazuki Owada; Naoya Yamashita; Kohtaro Takei; Yoshio Goshima; Toshio Ohshima

doi:10.1038/srep08269

Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation

Jun Nagai, Yoshiteru Kitamura, Kazuki Owada, Naoya Yamashita, Kohtaro Takei, Yoshio Goshima, Toshio Ohshima^*

^*Corresponding author for this work

School of Advanced Science and Engineering

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

30 Citations (Scopus)

Abstract

Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4^-/- mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI.

Original language	English
Article number	8269
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep08269
Publication status	Published - 2015 Feb 5

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title = "Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation",

abstract = "Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4-/- mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI.",

author = "Jun Nagai and Yoshiteru Kitamura and Kazuki Owada and Naoya Yamashita and Kohtaro Takei and Yoshio Goshima and Toshio Ohshima",

note = "Funding Information: We thank Dr. Christopher Quinn for providing anti-CRMP4b antibody and Dr. Joshua Sanes for providing GFP-M mice. This work was supported by grants from Grant-in-Aid for JSPS Fellows (J.N.), Global COE for Practical Chemical Wisdom Research Grant for Research Assistant (J.N.), JSPS KAKENHI Grant Number 26430043 (T.O.), and Waseda University Grant for Special Research Projects (2013B-171 to T.O.).",

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AU - Nagai, Jun

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AU - Takei, Kohtaro

AU - Goshima, Yoshio

AU - Ohshima, Toshio

N1 - Funding Information: We thank Dr. Christopher Quinn for providing anti-CRMP4b antibody and Dr. Joshua Sanes for providing GFP-M mice. This work was supported by grants from Grant-in-Aid for JSPS Fellows (J.N.), Global COE for Practical Chemical Wisdom Research Grant for Research Assistant (J.N.), JSPS KAKENHI Grant Number 26430043 (T.O.), and Waseda University Grant for Special Research Projects (2013B-171 to T.O.).

PY - 2015/2/5

Y1 - 2015/2/5

N2 - Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4-/- mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI.

AB - Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4-/- mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI.

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Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation

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