title: Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by contralateral nerve root transfer.
abstract: Lower extremity spasticity is a common sequela among patients with acquired brain injury. The optimum treatment remains controversial. The aim of our study was to test the feasibility and effectiveness of contralateral nerve root transfer in reducing post stroke spasticity of the affected hindlimb muscles in rats. In our study, we for the first time created a novel animal hindlimb spastic hemiplegia model in rats with photothrombotic lesion of unilateral motor cortex and we established a novel surgical procedure in reducing motor cortex lesion-induced hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three groups. In group A, rats received sham operation. In group B, rats underwent unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5 ventral root of the affected side. Footprint analysis, Hoffmann reflex (H-reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter 1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length recovered significantly in group C compared with group B (P<0.001). Hmax(H-wave maximum amplitude)/Mmax(M-wave maximum amplitude) ratio of gastrocnemius and plantaris muscles (PMs) significantly reduced in group C (P<0.01). Average VGLUT1 positive boutons per CTB-labelled motoneurons significantly reduced in group C (P<0.001). We demonstrated for the first time that contralateral L4 ventral root transfer to L5 ventral root of the affected side was effective in relieving unilateral motor cortex lesion-induced hindlimb spasticity in rats. Our data indicated that this could be an alternative treatment for unilateral lower extremity spasticity after brain injury. Therefore, contralateral neurotization may exert a potential therapeutic candidate to improve the function of lower extremity in patients with spastic hemiplegia.
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zong
authors.affiliation: Department of Pharmacy, Pudong Hospital, Fudan University, Shanghai 201399, China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, Linyi People's Hospital, Linyi 276000, China.
authors.forename: Laiyin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Pudong Hospital, Fudan University, Shanghai 201399, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, Pudong Hospital, Fudan University, Shanghai 201399, China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Pharmacy, Pudong Hospital, Fudan University, Shanghai 201399, China.
authors.forename: Min
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China.
authors.forename: Haodong
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China zhuyz@fudan.edu.cn yzzhu@must.edu.mo chunlinhou@126.com.|State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa Macau 999078, China.
authors.forename: Yizhun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China zhuyz@fudan.edu.cn yzzhu@must.edu.mo chunlinhou@126.com.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Hou
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000150:complications*; D004195:Disease Models, Animal; D006429:Hemiplegia / Q000209:etiology* / Q000601:surgery*; D006614:Hindlimb / Q000294:innervation*; D006801:Humans; D009044:Motor Cortex / Q000293:injuries*; D009046:Motor Neurons / Q000502:physiology; D009128:Muscle Spasticity / Q000209:etiology / Q000601:surgery; D018482:Muscle, Skeletal / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012021:Reflex, Abnormal / Q000502:physiology; D013126:Spinal Nerve Roots / Q000601:surgery*; D050598:Vesicular Glutamate Transport Protein 1 / Q000032:analysis
chemical_list: C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1
keywords: hindlimb; motor cortex; nerve transfer; spasticity