Study On Treatment Of Severe Brain Injury With Nanoparticles As Gene Carriers Of TNF-alpha Antisense Oligonucleotide

OBJECTIVE: In our study, we planned to deliver the TNF-α antisense oligonucleotide to central nervous system by intravenous administration with the help of carrier to treat severe traumatic brain injury. METHODS: Adult Sprague-Dawley rats(total 100) subjected to severe fluid-percussion TBI were randomized divided into four groups (25 rats per group) in in vivo experiments. The animal received one of the following injections: group 1 was intravenously injected with TNF-alpha-ASODN loaded nanooarticle suspension at a dose of 10 OD/Kg in tail vein, group 2(controled group) was intravenously injected with free TNF-alpha-ASODN at a dose of 10 OD/Kg in tail vein, group 3 was intracisternally injected with TNF-alpha-ASODN loaded nanooarticle suspension at a dose of 1 OD/Kg in cerebellomedullary cisten, group 4(controled group) was intracisternally injected with free TNF-alpha-ASODN at a dose of 1 OD/Kg in cerebellomedullary cisten. the rats were killed 3,6.12,24,72hr after the trauma. Brain samples were dissected out to detect TNF-α protein production by immunohistochemistry and to detect TNF-α mRNA expression by in situ hybridization and to measure the contents of H₂O in the injured brain. RESULTS: compared with control group(TNF-alpha-ASODN loaded nanooarticle by cistern), the contents of H₂O and TNF-α protein production in the injured brain were significantly discreased(p<0.05) at post-trauma with TNF-alpha-ASODN loaded nanoparticles by routine vein administration. CONCLUSION: The therapeutic effect of TNF-alpha-ASODN loaded nanooarticle suspension by may be parallel to or better by routine vein administration than that by cistern.