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Molecular Neurobiology

, Volume 55, Issue 1, pp 652–667 | Cite as

TAT-PEP Enhanced Neurobehavioral Functional Recovery by Facilitating Axonal Regeneration and Corticospinal Tract Projection After Stroke

  • Bin Deng
  • Liya Li
  • Xingchun Gou
  • Hao Xu
  • Zhaohua Zhao
  • Qiang WangEmail author
  • Lixian XuEmail author
Article

Abstract

Paired immunoglobulin-like receptor B (PirB) has been identified as a new receptor for myelin-associated inhibitory (MAI) proteins, which may play important role in axonal regeneration and corticospinal tract (CST) projection associated with neurobehavioral function recovery after stroke. Here, we found that the expression of PirB was increased in the cortical penumbra from 1 to 28 days after transient focal cerebral ischemic reperfusion of rats. Then, transactivator of transcription-PirB extracellular peptide (TAT-PEP) was generated that might block the interactions between MAIs and PirB. The results showed that TAT-PEP displayed high affinity for MAIs and ameliorated their inhibitory effect on neurite growth. Furthermore, TAT-PEP can widely distribute in the penumbra after intraperitoneal injection. Then, we found that TAT-PEP enhanced neurite growth and alleviated growth cone collapse after oxygen glucose deprivation (OGD) injury. In addition, TAT-PEP promoted long-term neurobehavioral functional recovery through enhancing axonal regeneration and CST projection. Finally, the observations demonstrated that POSH/RhoA/growth-associated protein 43 (GAP43) as PirB-associated downstream signaling molecules played important role in neurobehavioral functional recovery after stroke. Moreover, the underlying mechanism associated with TAT-PEP-mediated promoting axonal regeneration and CST projection was by intervening in the expression of POSH, RhoA, and GAP43. These studies suggest that TAT-PEP may represent an attractive therapeutic strategy against stroke.

Keywords

Stroke Paired immunoglobulin-like receptor B Transactivator of transcription domain Axonal regeneration Corticospinal tract projection 

Abbreviations

SD

Sprague-Dawley

MCAO

Middle cerebral arterial occlusion

PirB

Paired immunoglobulin-like receptor B

TTC

2,3,5-Triphenyltetrazolium chloride

CST

Corticospinal tract

OGD

Oxygen glucose deprivation

NF-200

Neurofilament 200

GAP43

Growth-associated protein 43

MEP

Motor evoked potential

Notes

Acknowledgements

The authors thank Mr. Shiquan Wang for his surgical assistance with the MCAO model and Dr. Shun Qi for his technical assistance with MRI. This manuscript was edited for English language use by American Journal Experts. This work was supported by the General Projects of the National Natural Science Foundation of China (Grant Nos. 81501207, 81471265, 81471415, and 81473488).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2016_301_MOESM1_ESM.doc (293 kb)
ESM 1 (DOC 293 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Key Laboratory of Oral Diseases, Department of Anesthesiology, School of StomatologyFourth Military Medical UniversityXi’anChina
  2. 2.Department of AnesthesiologyThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  3. 3.Department of EmergencyThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
  4. 4.The Laboratory of Cell Biology and Translational MedicineXi’an Medical UniversityXi’anChina

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