TAT-PEP Enhanced Neurobehavioral Functional Recovery by Facilitating Axonal Regeneration and Corticospinal Tract Projection After Stroke
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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.
KeywordsStroke Paired immunoglobulin-like receptor B Transactivator of transcription domain Axonal regeneration Corticospinal tract projection
Middle cerebral arterial occlusion
Paired immunoglobulin-like receptor B
Oxygen glucose deprivation
Growth-associated protein 43
Motor evoked potential
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.
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