Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures

Botulinum-toxin A (BoNT/A) is used for a wide range of conditions. Intramuscular administration of BoNT/A inhibits the release of acetylcholine at the neuromuscular junction from presynaptic motor neurons causing muscle-paralysis. The aim of the present study was to investigate the effect of high dose intramuscular BoNT/A injections (6 UI = 60 pg) on muscle tissue. The gait pattern of the rats was significantly affected 3 weeks after BoNT/A injection. The ankle joint rotated externally, the rats became flat footed, and the stride length decreased after BoNT/A injection. Additionally, there was clear evidence of microstructural changes on the tissue level by as evidenced by 3D imaging of the muscles by Synchrotron Radiation X-ray Tomographic Microscopy (SRXTM). Both the fibrillar and the non-fibrillar tissues were affected. The volume fraction of fibrillary tissue was reduced significantly and the non-fibrillar tissue increased. This was accompanied by a loss of the linear structure of the muscle tissue. Furthermore, gene expression analysis showed a significant upregulation of COL1A1, MMP-2, TGF-b1, IL-6, MHCIIA and MHCIIx in the BoNT/A injected leg, while MHVIIB was significantly downregulated. In conclusion: The present study reveals that high dose intramuscular BoNT/A injections cause microstructural damage of the muscle tissue, which contributes to impaired gait.

Nielsen, Mikkel SchouUniversity of Copenhagen (författare)
Lauridsen, TorstenUniversity of Copenhagen (författare)
Rix, KristianUniversity of Copenhagen(Swepub:lu)kr1387ri (författare)
Bech, MartinLund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-mbh (författare)
Alkjaer, TineUniversity of Copenhagen (författare)
Andersen, Ida TorpUniversity of Copenhagen (författare)
Nielsen, Jens BoUniversity of Copenhagen (författare)
Feidenhansl, R.University of Copenhagen (författare)
University of CopenhagenMedicinsk strålningsfysik, Lund (creator_code:org_t)

Av författaren/redakt...: Pingel, Jessica; Nielsen, Mikkel ...; Lauridsen, Torst ...; Rix, Kristian; Bech, Martin; Alkjaer, Tine; visa fler...; Andersen, Ida To ...; Nielsen, Jens Bo; Feidenhansl, R.; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Fysiologi

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.