Recovery after spinal cord injury by modulation of the proteoglycan receptor PTPσ

  • Exp Neurol. 2018 Nov:309:148-159. doi: 10.1016/j.expneurol.2018.08.003.
Svenja Rink  1 ,  Dominik Arnold  2 ,  Aliona Wöhler  3 ,  Habib Bendella  4 ,  Carolin Meyer  5 ,  Marilena Manthou  6 ,  Theodora Papamitsou  7 ,  Levent Sarikcioglu  8 ,  Doychin N Angelov  9
Affiliations
  • 1. Department of Prosthetic Dentistry, School of Dental and Oral Medicine, University of Cologne, Cologne, Germany.
  • 2. Department of Anatomy I, University of Cologne, Germany.
  • 3. Bundeswehrzentralkrankenhaus, Koblenz, Germany.
  • 4. Department of Neurosurgery, University of Witten/Herdecke, Cologne Merheim Medical Center (CMMC), Cologne, Germany. Electronic address: [email protected].
  • 5. Department of Orthopedics and Trauma Surgery, University of Cologne, Germany. Electronic address: [email protected].
  • 6. Department of Histology and Embryology, Aristotle University Thessaloniki, Greece.
  • 7. Department of Histology and Embryology, Aristotle University Thessaloniki, Greece. Electronic address: [email protected].
  • 8. Department of Anatomy, Faculty of Medicine, Akdeniz University, Antalya, Turkey. Electronic address: [email protected].
  • 9. Department of Anatomy I, University of Cologne, Germany. Electronic address: [email protected].
PMID: 30118740 DOI: 10.1016/j.expneurol.2018.08.003
Abstract

SCI is followed by dramatic upregulation of chondroitin sulfate proteoglycans (CSPGs) which limit axonal regeneration, oligodendrocyte replacement and remyelination. The recent discovery of the specific CSPGs signaling receptor protein tyrosine Phosphatase sigma (RPTPσ) provided an opportunity to refine the therapeutic approach to overcome CSPGs inhibitory actions. In previously published work, subcutaneous (s.c.) delivery of 44 μg/day of a peptide mimetic of PTPσ called intracellular sigma peptide (ISP), which binds to PTPσ and blocks CSPG-mediated inhibition, facilitated recovery after contusive SCI. Since this result could be of great interest for clinical trials, we independently repeated this study, but modified the method of injury as well as peptide application and the dosage. Following SCI at the Th10-segment, 40 rats were distributed in 3 groups. Animals in group 1 (20 rats) were subjected to SCI, but received no treatment. Rats in group 2 were treated with intraperitoneal (i.p.) injections of 44 μg/day ISP (SCI + ISP44) and Animals of group 3 with s.c. injections of 500 μg/day ISP (SCI + ISP500) for 7 weeks after lesioning. Recovery was analyzed at 1, 3, 6, 9 and 12 weeks after SCI by determining (i) BBB-score, (ii) foot-stepping angle, (iii) rump-height index, (iv) number of correct ladder steps, (v) bladder score and (vi) sensitivity (withdrawal latency after thermal stimulus). Finally, we determined the amount of serotonergic fibers in the preserved neural tissue bridges (PNTB) around the lesion site. Our results show that, systemic therapy with ISP improved locomotor, sensory and vegetative recovery which correlated with more spared serotonergic fibers in PNTB.

Keywords
Bladder and sensory function; CSPG; ISP; Locomotor; PTPσ; Rat; Serotonin; Spinal cord injury.
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