title: RNA interference against repulsive guidance molecule A improves axon sprout and neural function recovery of rats after MCAO/reperfusion.
abstract: Repulsive guidance molecule a (RGMa) is a neurite growth inhibitor that is of great interest in the study of CNS neuronal regeneration. We adopted RNA interference (RNAi) as a means of suppressing the expression of RGMa and observed the improvement in axonal regeneration and neurological function of rats after cerebral ischemic injury. Recombinant adenovirus rAd5-shRNA-RGMa was constructed and prepared for animal experimentation. RGMa and neurofilament protein 200 (NF200) in the ischemic cortex and ipsilateral hippocampus were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The ischemic regions were examined by triphenyltetrazolium chloride (TTC) staining and the newborn neurite branches by Biotinylated Dextran Amine (BDA) neuronal tracing. Behavior tests were adopted to evaluate neurologic function recovery. Results showed RGMa was down-regulated and axonal growth was improved in the RNAi treated group (P<0.01). The number of axonal sprouts of corticospinal tract from the uninjured side to the ischemic side in the RNAi treated group was increased (P<0.01). Behavior test scores in the RNAi treated group were significantly better than other groups after 6 weeks (P<0.01). RGMa in rat brains after middle cerebral artery occlusion (MCAO) can be down-regulated by RNAi successfully, which may lead to improved axonal growth and neural anatomy plasticity, as well as neuron functional recovery.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, The People's Republic of China. fengjinzhou@hotmail.com
authors.forename: Jinzhou
authors.initials: J
authors.lastname: Feng
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wu
authors.forename: Xinyue
authors.initials: X
authors.lastname: Qin
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D001710:Biotin / Q000031:analogs & derivatives; D020520:Brain Infarction / Q000378:metabolism / Q000517:prevention & control; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003911:Dextrans; D004195:Disease Models, Animal; D005116:Extrapyramidal Tracts / Q000378:metabolism / Q000473:pathology; D007839:Functional Laterality / Q000502:physiology; D058851:GPI-Linked Proteins; D020233:Gait Disorders, Neurologic / Q000175:diagnosis / Q000209:etiology; D005786:Gene Expression Regulation / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology / Q000628:therapy*; D053583:Interleukin-1beta / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology*; D012039:Regional Blood Flow; D015424:Reperfusion; D013238:Stereotaxic Techniques; D013778:Tetrazolium Salts; D013997:Time Factors
chemical_list: D003911:Dextrans; D058851:GPI-Linked Proteins; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C502259:RGM protein, rat; D012333:RNA, Messenger; D013778:Tetrazolium Salts; C076397:biotinylated dextran amine; D049452:Green Fluorescent Proteins; D001710:Biotin; C009591:triphenyltetrazolium