title: Regenerative repair of Pifithrin-α in cerebral ischemia via VEGF dependent manner.
abstract: Promoting regenerative repair, including neurogenesis and angiogenesis, may provide a new therapeutic strategy for treatment of stroke. P53, a well-documented transcription factor, has been reported to be involved in cerebral ischemia and also serves as an important regulator of vascular endothelial growth factor (VEGF). However, the role of p53 in endogenous regenerative repair after brain ischemia is poorly understood. In this study, we investigated the effects of PFT-α, a specific p53 inhibitor on neurogenesis and angiogenesis improvement and associated signal pathways in rats impaired by cerebral artery occlusion (MCAo). PFT-α induced neuroprotection, reduced infarct volume and neurological functional impairment after ischemic stroke. More importantly, neurogenesis and angiogenesis were greatly enhanced by PFT-α, and accompanied by increased expression of VEGF. Moreover, we got consistent results in neural stem cells (NSCs) isolated from fetal rats. In contrast, application of the anti-VEGF neutralizing antibody (RB-222) partially reversed PFT-α-induced neuroprotection and rescued p53 expression. Noteworthily, inhibition of p53 after ischemic stroke in these rats improved their outcomes via promotion of regenerative repair. In conclusion, PFT-α could serve as a promising therapeutic strategy for ischemic stroke by promoting regenerative repair.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Lei
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Chenlong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Daming
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Nishant
authors.initials: N
authors.lastname: Bhatta
authors.affiliation: Department of Cardiology and Clinical Pharmacy, Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin, China.
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Chuanlu
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D014050:Toluene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D052160:Benzothiazoles; D018696:Neuroprotective Agents; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D014050:Toluene; C121565:pifithrin