title: TAT-PEP Enhanced Neurobehavioral Functional Recovery by Facilitating Axonal Regeneration and Corticospinal Tract Projection After Stroke.
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.
authors.affiliation: 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 Stomatology, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.|Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Deng
authors.affiliation: Department of Emergency, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Li
authors.affiliation: The Laboratory of Cell Biology and Translational Medicine, Xi'an Medical University, Xi'an, 710021, China.
authors.forename: Xingchun
authors.initials: X
authors.lastname: Gou
authors.affiliation: The Laboratory of Cell Biology and Translational Medicine, Xi'an Medical University, Xi'an, 710021, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: 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 Stomatology, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China. wangqiangfmmu@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 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 Stomatology, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China. lixianxu2015@hotmail.com.
authors.forename: Lixian
authors.initials: L
authors.lastname: Xu
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000473:pathology; D005947:Glucose / Q000172:deficiency; D020439:Growth Cones / Q000378:metabolism; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen; D010455:Peptides / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D020127:Recovery of Function / Q000187:drug effects; D015398:Signal Transduction; D020521:Stroke / Q000473:pathology / Q000503:physiopathology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology*
chemical_list: D010455:Peptides; C491380:Pirb protein, rat; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D005947:Glucose; D010100:Oxygen
keywords: Axonal regeneration; Corticospinal tract projection; Paired immunoglobulin-like receptor B; Stroke; Transactivator of transcription domain