Neurotization Actuating Flexion and Extension Effectively Alleviates the Hindlimb Hemiplegia Caused by Hemorrhagic Stroke

Abstract

Background: Central hemiplegia led by hypertensive intracerebral hemorrhage(HICH) is prevalent, devastating, and currently unable to intervene satisfactorily. Here,to move toward the clinic,we explored whether contralateral L4 nerve transfer,centralizing at flexion and extension, reanimates fine motor function for hemiplegic hindlimbs after HICH. Methods: Eligible rat models were manufactured by injecting autologous vein blood into the posterior limb of internal capsule (PLIC).Thirty rats were randomized into three groups.Rats in group A underwent sham operation(i.e.,exposure of bi-L4 roots without severance) after injection of saline. Rats in group B and group C were infused equal blood followed by bilateral L4 nerve roots transection and contralateral L4 nerve transfer, respectively. Behavioural, ultrastructural, immunofluorescent, and electromyographic assessments were applied at a scheduled timepoint in our study. fMRI was used as localization of PLIC impact. Findings: Through neurotization, skilled motion produced by dexterous flexion and extension in major joints (hip, knee, and ankle) of the paralyzed hindlimb recovered more sharply in group C than in group B (P<0.001), with BBB scores increasing accordingly. Reinnervated potentials were significantly detected for denervated flexors or extensors in group C, compared with group B(P<0.05). Simultaneously, detached fore-hindpaw prints were converted to an approximate superposition in a temporally-improved fashion. Histological and ultra-microstructural assessments revealed that at the anastomosis point, numerous axons were generated, realigned, and remyelinated over time. Interpretation: Neurotization involving contralateral L4 transfer activates robust flexion and extension, and efficaciously repairs the hemiplegic hindlimb after HICH. Funding Statement: This study was supported by grants from the National Natural Science Foundation of China (No. 81171147), “Key Medical Talents of Qiangwei Project” Research Foundation of Health Department of Jiangsu Province (No. ZDRCA2016010), “Xingwei Project” Key Personal Medical Research Foundation of Health Department of Jiangsu Province (No. RC201156), Jiangsu Province’s Natural Science Foundation (BK20171064), Research Foundation of Jiangsu Provincial Medical Youth Talent, the Project of Invigorating Health Care through Science, Technology and Education (QNRC2016858). Jiangsu Province’s Key Discipline of Medicine (No. XK201117) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Declaration of Interests: All authors report no disclosures relevant to the manuscript, and claim no conflict of interests. Ethics Approval Statement: Animal experiments were conducted in accordance with the principles and procedures outlined in the NIH Guide for the Care and Use of Laboratory Animals (National Academies Press, 2011). Procedures concerning animals were approved by the Institutional Animal Care and Use Committee at Nanjing Medical University (Nanjing,Jiangsu,China;approval no. IACUC-1906009).