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.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Rink S,Arnold D,Wöhler A,Bendella H,Meyer C,Manthou M,Papamitsou T,Sarikcioglu L,Angelov DNdoi
10.1016/j.expneurol.2018.08.003subject
Has Abstractpub_date
2018-11-01 00:00:00pages
148-159eissn
0014-4886issn
1090-2430pii
S0014-4886(18)30337-6journal_volume
309pub_type
杂志文章abstract::Electrical stimulation of the midbrain tegmentum can produce differential modulation of quiet biting attack and affective defense behavior elicited from the hypothalamus of the cat. Stimulation of the lateral half of the tegmentum facilitated quiet biting attack and suppressed affective defense. Conversely, stimulatio...
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