Universität zu Köln

Rink, Svenja, Arnold, Dominik, Woehler, Aliona, Bendella, Habib, Meyer, Carolin, Manthou, Marilena, Papamitsou, Theodora, Sarikcioglu, Levent and Angelov, Doychin N. (2018). Recovery after spinal cord injury by modulation of the proteoglycan receptor PTP sigma. Exp. Neurol., 309. S. 148 - 160. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1090-2430

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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 (RPTP sigma) provided an opportunity to refine the therapeutic approach to overcome CSPGs inhibitory actions. In previously published work, subcutaneous (s.c.) delivery of 44 mu g/day of a peptide mimetic of PTP sigma called intracellular sigma peptide (ISP), which binds to PTP sigma 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 mu g/day ISP (SCI + ISP44) and animals of group 3 with s.c. injections of 500 mu g/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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rink, Svenja UNSPECIFIED UNSPECIFIED UNSPECIFIED Arnold, Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED Woehler, Aliona UNSPECIFIED UNSPECIFIED UNSPECIFIED Bendella, Habib UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Carolin UNSPECIFIED UNSPECIFIED UNSPECIFIED Manthou, Marilena UNSPECIFIED UNSPECIFIED UNSPECIFIED Papamitsou, Theodora UNSPECIFIED UNSPECIFIED UNSPECIFIED Sarikcioglu, Levent UNSPECIFIED UNSPECIFIED UNSPECIFIED Angelov, Doychin N. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-168707
DOI:	10.1016/j.expneurol.2018.08.003
Journal or Publication Title:	Exp. Neurol.
Volume:	309
Page Range:	S. 148 - 160
Date:	2018
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1090-2430
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHONDROITIN SULFATE PROTEOGLYCAN; EXTERNAL URETHRAL SPHINCTER; LOWER URINARY-TRACT; FUNCTIONAL RECOVERY; GLIAL SCAR; RATS; BLADDER; PROMOTES; COMPRESSION; GROWTH Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16870