Gene treatment of cerebral stroke by rAAV vector delivering IL-1ra in a rat model.
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.
Tsai
Tung-Han
TH
Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Chen
Show-Li
SL
Xiao
Xiao
X
Chiang
Yung-Hsiao
YH
Lin
Shinn-Zong
SZ
Kuo
Shu-Wen
SW
Liu
Dai-Wei
DW
Tsao
Yeou-Ping
YP
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
D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins