Lasting Peripheral and Central Effects of Botulinum Toxin Type A on Experimental Muscle Hypertonia in Rats

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• Autor: Petra Šoštarić
• Autor: Barbara Vukić
• Autor: Lea Tomašić
• Autor: Ivica Matak
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (KATEDRA ZA TEMELJNU I KLINIČKU FARMAKOLOGIJU)
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti; Farmakologija

Sažetak (engleski)

Recent animal experiments suggested that centrally transported botulinum toxin type A (BoNT-A) might reduce an abnormal muscle tone, though with an unknown contribution to the dominant peripheral muscular effect observed clinically. Herein, we examined if late BoNT-A antispastic actions persist due to possible central toxin actions in rats. The early effect of intramuscular (i.m.) BoNT-A (5, 2 and 1 U/kg) on a reversible tetanus toxin (TeNT)-induced calf muscle spasm was examined 7 d post-TeNT and later during recovery from flaccid paralysis (TeNT reinjected on day 49 post-BoNT-A). Lumbar intrathecal (i.t.) BoNT-A–neutralizing antiserum was used to discriminate the transcytosis-dependent central toxin action of 5 U/kg BoNT-A. BoNT-A-truncated synaptosomal-associated protein 25 immunoreactivity was examined in the muscles and spinal cord at day 71 post-BoNT-A. All doses (5, 2 and 1 U/kg) induced similar antispastic actions in the early period (days 1–14) post-BoNT-A. After repeated TeNT, only the higher two doses prevented the muscle spasm and associated locomotor deficit. Central trans-synaptic activity contributed to the late antispastic effect of 5 U/kg BoNT-A. Ongoing BoNT-A enzymatic activity was present in both injected muscle and the spinal cord. These observations suggest that the treatment duration in sustained or intermittent muscular hyperactivity might be maintained by higher doses and combined peripheral and central BoNT-A action.

• Ključne riječi (engleski): Animals; Botulinum Toxins, Type A / pharmacology; Muscle Hypertonia / drug therapy; Rats; Spasm / drug therapy; Synaptosomal-Associated Protein 25 / metabolism; Tetanus Toxin / metabolism; Tetanus Toxin / pharmacology
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: International Journal of Molecular Sciences
• Brojčani podaci: vol. 23, br. 19, 11626
• e-ISSN: 1422-0067
• DOI: https://doi.org/10.3390/ijms231911626
• URN:NBN: urn:nbn:hr:105:343506
• Datum objave publikacije: 2022-10-01
• Projekt: Šifra: UIP-2019-04-8277; Naziv (hrvatski): Motorički učinci klostridijskih neurotoksina u središnjem živčanom sustavu; Naziv (engleski): Motor effects of clostridial neurotoxins in central nervous system; Kratica: MEFCLO; Voditelj: Ivica Matak; Pravna nadležnost: Hrvatska; Financijer: HRZZ; Linija financiranja: UIP
• URL dokumenta: https://www.mdpi.com/1422-0067/23/19/11626
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2023-08-22 08:48:51