Contemporary treatments (Myelotomy, Riluzole, Whole-Body Vibration) to improve neural regeneration and functional recovery after spinal-cord compression injury (SCI) in rats

Abstract

Recently we showed in rats that WBV with an onset of 14 days after SCI improved body weight support, increased the density of synaptic terminals in the lumbar spinal cord and restored bladder function. In a subsequent experimental set, WBV was combined with medial longitudinal myelotomy (MLM) which - by removal of neural debris from the lesion site - should reduce secondary injury. In a further experiment, SCI-rats were subjected to WBV+MLM and treated with Riluzole, which - by blocking voltage-sensitive sodium channels antagonizes the presynaptic release of glutamate - should reduce excitotoxicity.In the first experiment, severe compression SCI at low-thoracic level (Th10) was followed by MLM 48 h later. All rats were subjected to daily WBV over a 12-week post-injury period. Recovery of locomotion was analyzed at 1, 3, 6, 9, and 12 weeks after SCI. We measured: (i) BBB-locomotor score, (ii) foot-stepping angle (FSA), (iii) rump-height index (RHI), (iv) number of correct ladder steps (CLS), (v) bladder score and (vi) changes in the sensitivity of the hindlimbs. Lesion volume and intensity of immunofluorescence for astrogliosis (GFAP), microglia (IBA1) and synaptic vesicles (synaptophysin, SYN) below the lesion (segment L2) were determined after perfusion fixation. The only change in the second experiment was that WBV+ MLM were extended by treatment with Riluzole (RLZ; 8 mg/kg) i.p., for the first 7 days after SCI.Compared to rats treated with WBVonly, the combinations of WBV+MLM and WBV+MLM+RLZ did not improve any functional parameter during the 12-week period. Our results thus do not support current evidence for a beneficial effect of Riluzole on recovery after SCI. Accordingly, neither combination reduced lesion volume and the intensity of glial reactions (astro- and microglia). The amount of synapses in the ventral horn below the lesion did not differ from that in rats with WBVonly. We conclude that MLM+WBV does not improve functional and morphological parameters after SCI. At the same time however, it did not worsen the values, which in turn may be a prerequisete for future studies with direct intramedullary appilcation of drugs to the lesion site after SCI.