title: Gene treatment of cerebral stroke by rAAV vector delivering IL-1ra in a rat model.
abstract: In this study, we injected recombinant adeno-associated virus (rAAV) vectors expressing the interleukin-1 receptor antagonist (rAAV-IL-1ra) into the cortex of rats experiencing transient cerebral ischemia. An accumulation of IL-1ra in cortical tissues of rAAV-IL-1ra-injected animals was confirmed by ELISA. Triphenyltetrazolium chloride (TTC) staining of viable brain tissue revealed that the rAAV-delivered IL-1ra gene could rescue the brain tissues from ischemia-induced injury. Cortical tissues that received rAAV-IL-1ra injections had both significantly smaller total volumes of infarction as well as smaller areas of infarction on each brain slice when compared with the control models. In situ labeling analysis demonstrated significant reduction of apoptotic cells in cortical tissues rescued by rAAV-IL-1ra. Immunohistochemistry staining revealed that the rescued brain tissues contained the same levels of neuronal cells as contralateral undamaged brain tissues. These findings confirmed that the rAAV delivering the IL-1ra gene is a potential therapy for stroke.
authors.affiliation: Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Tung-Han
authors.initials: TH
authors.lastname: Tsai
authors.forename: Show-Li
authors.initials: SL
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.forename: Yung-Hsiao
authors.initials: YH
authors.lastname: Chiang
authors.forename: Shinn-Zong
authors.initials: SZ
authors.lastname: Lin
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Kuo
authors.forename: Dai-Wei
authors.initials: DW
authors.lastname: Liu
authors.forename: Yeou-Ping
authors.initials: YP
authors.lastname: Tsao
mesh_terms: D000818:Animals; D000229:Dependovirus; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy; D005822:Genetic Vectors; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D053590:Interleukin 1 Receptor Antagonist Protein; D002546:Ischemic Attack, Transient / Q000628:therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012795:Sialoglycoproteins / Q000627:therapeutic use*; D020521:Stroke / Q000628:therapy
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins