title: Asynchronous therapy targeting Nogo-A enhances neurobehavioral recovery by reducing neuronal loss and promoting neurite outgrowth after cerebral ischemia in mice.
abstract: Therapeutics targeting the Nogo-A signal pathway hold promise to promote recovery following brain injury. Based on the temporal characteristics of Nogo-A expression in the process of cerebral ischemia and reperfusion, we tested a novel asynchronous treatment, in which TAT-M9 was used in the early stage to decrease neuronal loss, and TAT-NEP1-40 was used in the delayed stage to promote neurite outgrowth after bilateral common carotid artery occlusion (BCCAO) in mice. Both TAT-M9 and TAT-NEP1-40 were efficiently delivered into the brains of mice by intraperitoneal injection. TAT-M9 treatment promoted neuron survival and inhibited neuronal apoptosis. Asynchronous therapy with TAT-M9 and TAT-NEP1-40 increased the expression of Tau, GAP43 and MAP-2 proteins, and enhanced short-term and long-term cognitive functions. In conclusion, the asynchronous treatment had a long-term neuroprotective effect, which reduced neurologic injury and apoptosis, promoted neurite outgrowth and enhanced functional recovery after ischemia. It suggests that this asynchronous treatment could be a promising therapy for cerebral ischemia in humans.
authors.affiliation: a Department of Anesthesiology , Xijing Hospital, Fourth Military Medical University , Xi' an , China .|b Department of Emergency , The Second Affiliated Hospital of Dalian Medical University , Dalian , China .
authors.forename: Liya
authors.initials: L
authors.lastname: Li
authors.affiliation: c Department of Anesthesiology , State Key Laboratory of Military Stomatology, School of Stomatology, Fourth Military Medical University , Xi'an , China , and.
authors.forename: Bin
authors.initials: B
authors.lastname: Deng
authors.affiliation: a Department of Anesthesiology , Xijing Hospital, Fourth Military Medical University , Xi' an , China .
authors.forename: Shiquan
authors.initials: S
authors.lastname: Wang
authors.affiliation: a Department of Anesthesiology , Xijing Hospital, Fourth Military Medical University , Xi' an , China .
authors.forename: Haixing
authors.initials: H
authors.lastname: Zhong
authors.affiliation: a Department of Anesthesiology , Xijing Hospital, Fourth Military Medical University , Xi' an , China .
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: d Institute of Neurosciences, School of Life Sciences and Biotechnology, Jiao Tong University , Shanghai , China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Jin
authors.affiliation: a Department of Anesthesiology , Xijing Hospital, Fourth Military Medical University , Xi' an , China .
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: b Department of Emergency , The Second Affiliated Hospital of Dalian Medical University , Dalian , China .
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: a Department of Anesthesiology , Xijing Hospital, Fourth Military Medical University , Xi' an , China .
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000067290:Behavior Rating Scale; D002545:Brain Ischemia / Q000503:physiopathology*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D019922:GAP-43 Protein / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009185:Myelin Proteins / Q000008:administration & dosage / Q000187:drug effects* / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000070798:Nogo Proteins; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000503:physiopathology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D019922:GAP-43 Protein; D008869:Microtubule-Associated Proteins; D009185:Myelin Proteins; C509624:NEP1-40 protein, human; D018696:Neuroprotective Agents; D000070798:Nogo Proteins; D010446:Peptide Fragments; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: Global cerebral ischemia; Nogo-66 receptor; Nogo-A; neurite regeneration; neurological function recovery