Evidence for central antispastic effect of botulinum toxin type

Znanstveni rad - Izvorni znanstveni rad

• 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)

Background and Purpose Botulinum toxin type A (BoNT/A) injections into hyperactive muscles provide effective treatment for spasticity and dystonias, presumably due to its local effects on extrafusal and intrafusal motor fibres. A recent discovery of toxin's retrograde axonal transport to CNS might suggest additional action sites. However, in comparison to cholinergic peripheral terminals, functional consequences of BoNT/A direct central action on abnormally increased muscle tone are presently unknown. To address this question, the central effects of BoNT/A were assessed in experimental local spastic paralysis. ----- Experimental Approach
Local spastic paralysis was induced by injection of tetanus toxin (1.5 ng) into rat gastrocnemius. Subsequently, BoNT/A (5 U·kg−1) was applied i.m. into the spastic muscle or intraneurally (i.n.) into the sciatic nerve to mimic the action of axonally transported toxin. Functional role of BoNT/A transcytosis in spinal cord was evaluated by lumbar i.t. application of BoNT/A‐neutralizing antitoxin. BoNT/A effects were studied by behavioural motor assessment and cleaved synaptosomal‐associated protein 25 (SNAP‐25) immunohistochemistry. ----- Key Results Tetanus toxin evoked muscular spasm (sustained rigid hind paw extension and resistance to passive ankle flexion). Subsequent injections of BoNT/A, i.m. or i.n, reduced tetanus toxin‐evoked spastic paralysis. Beneficial effects of i.n. BoNT/A and occurrence of cleaved SNAP‐25 in ventral horn were prevented by i.t. antitoxin. ----- Conclusions and Implications Axonally transported BoNT/A relieves muscle hypertonia induced by tetanus toxin, following the trans‐synaptic movement of BoNT/A in the CNS. These results suggest that such direct, centrally mediated reduction of abnormal muscle tone might contribute to the effectiveness of BoNT/A in spasticity and hyperkinetic movement disorders.

• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Završna verzija rukopisa prihvaćena za objavljivanje (postprint)
• Naslov časopisa: British Journal of Pharmacology
• Brojčani podaci: vol. 177, br. 1, str. 65-76
• p-ISSN: 0007-1188
• e-ISSN: 1476-5381
• DOI: https://doi.org/10.1111/bph.14846
• URN:NBN: urn:nbn:hr:105:425846
• Datum objave publikacije: 2020-01
• URL dokumenta: https://onlinelibrary.wiley.com/doi/abs/10.1111/bph.14846
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup; Datum isteka embarga: 2022-02-02
• Datum i vrijeme pohrane: 2021-01-11 10:02:59