Whole body vibration (WBV) following spinal cord injury (SCI) in rats: Timing of intervention

Article type: Research Article

Authors: Manthou, Marilena^{a; 1} | Abdulla, Diana Saad Yousif^{b; 1} | Pavlov, Stoyan Pavlov^{c; 1} | Jansen, Ramona^b | Bendella, Habib^d | Nohroudi, Klaus^b | Stein, Gregor^e | Meyer, Carolin^e | Ozsoy, Ozlem^f | Ozsoy, Umut^g | Behram Kandemir, Yasemin^g | Sarikcioglu, Levent^g | Semler, Oliver^h | Schoenau, Eckhard^h | Dunlop, Sarah^{i; 2} | Angelov, Doychin Nikolov^{b; 2; *}

Affiliations: [a] Department of Histology and Embryology, Aristotle University Thessaloniki, Greece | [b] Department of Anatomy I, University of Cologne, Germany | [c] Department of Anatomy, Medical University Varna, Bulgaria | [d] Department of Neurosurgery, University of Witten/Herdecke, Cologne Merheim Medical Center (CMMC), Cologne, Germany | [e] Department of Orthopedics and Trauma Surgery, University of Cologne, Germany | [f] Department of Physiology, Faculty of Medicine, Akdeniz University, Antalya, Turkey | [g] Department of Anatomy, Faculty of Medicine, Akdeniz University, Antalya, Turkey | [h] Children’s Hospital, University of Cologne, Germany | [i] Experimental and Regenerative Neuroscience, School of Animal Biology, The University of Western Australia, WA, Australia

Correspondence: [*] Corresponding author:Prof. Doychin N. Angelov, Institut 1 für Anatomie der Universität zu Köln, Joseph-Stelzmann-Strasse 20, D-50931 Köln, Germany; Tel.: +49 221 478 5654; Fax: +49 221 478 87893; E-mail: [email protected].

Note: [1] These authors contributed equally and share first authorship.

Note: [2] These authors contributed equally and share senior authorship.

Abstract: Background: Following spinal cord injury (SCI), exercise training provides a wide range of benefits and promotes activity-dependent synaptic plasticity. Whole body vibration (WBV) in SCI patients improves walking and spasticity as well as bone and muscle mass. However, little is known about the effects of timing or frequency of intervention. Objective: To determine which WBV-onset improves locomotor and bladder functions and influences synaptic plasticity beneficially. Methods: SCI was followed by WBV starting 1, 7, 14, 28 days after injury (WBV1, WBV7, etc.) and continued for 12 weeks. Intact animals and those receiving SCI but no WBV (No WBV), SCI plus WBV twice daily (2×WBV) and SCI followed by passive hindlimb flexion-extension (PFE) served as controls. Locomotor [BBB rating, foot stepping angle (FSA) and rump-height index (RHI)] as well as bladder function were determined at 1, 3, 6, 9, and 12 weeks. Following perfusion fixation at 12 weeks, lesion volume and immunofluorescence for astrogliosis (GFAP), microglia (IBA1) and synaptic vesicles (synaptophysin, SYN) were determined. Results: Compared to the No WBV group, the WB7 and WBV14 groups showed significantly faster speeds of BBB score recovery though this effect was temporary. Considering RHI we detected a sustained improvement in the WBV14 and PFE groups. Bladder function was better in the WBV14, WBV28, 2×WBV and PFE groups. Synaptophysin levels improved in response to WBV7 and WBV14, but worsened after WBV28 in parallel to an increased IBA1 expression. Correlation- and principal components analysis revealed complex relationships between behavioural (BBB, FSA, RHI) and morphological (GFAP, IBA1, SYN) measurements. Conclusions: WBV started 14 days after SCI provides the most benefit (RHI, bladder); starting at 1day after SCI provides no benefit and starting at 28 days may be detrimental. Increasing the intensity of WBV to twice daily did not provide additional benefit.

Keywords: Spinal cord injury, whole body vibration, synaptic plasticity, locomotor and bladder function recovery, astroglia, microglia, immunofluorescence

DOI: 10.3233/RNN-160691

Journal: Restorative Neurology and Neuroscience, vol. 35, no. 2, pp. 185-216, 2017