RNA interference against repulsive guidance molecule A improves axon sprout and neural function recovery of rats after MCAO/reperfusion

• Published in: Experimental neurology 2012-12, Vol.238 (2), p.235-242
• Main Authors: Feng, Jinzhou, Wang, Tianzhu, Li, Qi, Wu, Xiaohui, Qin, Xinyue
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Analysis of Variance; Animals; Axonal growth; Axons - metabolism; Axons - pathology; Biological and medical sciences; Biotin - analogs & derivatives; Brain Infarction - metabolism; Brain Infarction - prevention & control; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Dextrans; Disease Models, Animal; Extrapyramidal Tracts - metabolism; Extrapyramidal Tracts - pathology; Functional Laterality - physiology; Gait Disorders, Neurologic - diagnosis; Gait Disorders, Neurologic - etiology; Gene Expression Regulation - physiology; Green Fluorescent Proteins - genetics; Hippocampus - metabolism; Hippocampus - pathology; Humans; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - pathology; Infarction, Middle Cerebral Artery - therapy; Injuries of the nervous system and the skull. Diseases due to physical agents; Interleukin-1beta - metabolism; Laser-Doppler Flowmetry; Male; MCAO; Medical sciences; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neural function; Neurology; Pyramidal Tracts - metabolism; Pyramidal Tracts - pathology; Rats; Rats, Sprague-Dawley; Recovery of Function - genetics; Recovery of Function - physiology; Regional Blood Flow; Reperfusion; RGMa; RNA Interference - physiology; RNA, Messenger - metabolism; RNAi; Stereotaxic Techniques; Tetrazolium Salts; Time Factors; Traumas. Diseases due to physical agents
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2012.08.014

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