New Xymedon Analogues for Stimulation of Posttraumatic Regeneration of the Spinal Cord in Rats

T V Povysheva; V E Semenov; I V Galyametdinova; V S Reznik; K S Knni; P E Kolesnikov; Yu A Chelyshev

doi:10.1007/s10517-016-3580-2

New Xymedon Analogues for Stimulation of Posttraumatic Regeneration of the Spinal Cord in Rats

Bull Exp Biol Med. 2016 Dec;162(2):220-224. doi: 10.1007/s10517-016-3580-2. Epub 2016 Dec 1.

Authors

T V Povysheva¹, V E Semenov², I V Galyametdinova², V S Reznik², K S Knni³, P E Kolesnikov³, Yu A Chelyshev³

Affiliations

¹ Laboratory of Nucleobases Chemistry, A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of Russian Academy of Sciences, Kazan, Russia. t.povysheva@gmail.com.
² Laboratory of Nucleobases Chemistry, A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of Russian Academy of Sciences, Kazan, Russia.
³ Department of Histology, Cytology and Embryology, Kazan State Medical University of Ministry of Health of Russian Federation, Kazan, Russia.

PMID: 27905041
DOI: 10.1007/s10517-016-3580-2

Abstract

Effect of systemic administration of synthetic pyrimidine derivatives, xymedon and compounds 29D and 34D, was studied in rats with experimental dosed contusion spinal cord injury. Xymedon promoted recovery of motor function after injury. Compounds 29D and 34D more effectively restored the parameters of open-field and Rotarod tests in comparison with xymedon. Compound 29D more effectively than xymedon maintained the number of Olig2⁺ oligodendrocytes in the corticospinal tract and NG2 cells in all investigated areas of the white matter. In the group treated with compound 34D, the differences in the number of NG2⁺ cells were revealed only in the anterior funiculi, where the number of these glial cells was 2-fold higher than in the xymedon-treated group. Obtained results suggest that the studied xymedon analogs, compounds 29D and 34D, can exert their therapeutic action through different molecular and cellular pathways.

Keywords: pyrimidine; spinal cord injury; xymedon.

MeSH terms

Animals
Antigens / genetics
Antigens / metabolism
Basic Helix-Loop-Helix Transcription Factors / genetics
Basic Helix-Loop-Helix Transcription Factors / metabolism
Biomarkers / metabolism
Cell Count
Gene Expression
Nerve Fibers, Myelinated / drug effects
Nerve Fibers, Myelinated / metabolism
Nerve Fibers, Myelinated / pathology
Nerve Regeneration / drug effects*
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Neuroglia / drug effects
Neuroglia / metabolism
Neuroglia / pathology
Neuroprotective Agents / chemical synthesis
Neuroprotective Agents / pharmacology*
Oligodendrocyte Transcription Factor 2
Oligodendroglia / drug effects
Oligodendroglia / metabolism
Oligodendroglia / pathology
Proteoglycans / genetics
Proteoglycans / metabolism
Pyrimidines / chemical synthesis
Pyrimidines / pharmacology*
Rats
Rats, Wistar
Recovery of Function / drug effects*
Rotarod Performance Test
Spinal Cord / drug effects*
Spinal Cord / metabolism
Spinal Cord / pathology
Spinal Cord Injuries / drug therapy*
Spinal Cord Injuries / metabolism
Spinal Cord Injuries / pathology
White Matter / drug effects
White Matter / metabolism
White Matter / pathology

Substances

Antigens
Basic Helix-Loop-Helix Transcription Factors
Biomarkers
Nerve Tissue Proteins
Neuroprotective Agents
Olig2 protein, rat
Oligodendrocyte Transcription Factor 2
Proteoglycans
Pyrimidines
chondroitin sulfate proteoglycan 4
xymedon