Naslov
Long-term effects of botulinum neurotoxin type A on experimental muscle hypertonia
(Long-term effects of botulinum neurotoxin type A on experimental muscle hypertonia)

Autori
Matak, Ivica ; Šoštarić, Petra

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Toxicon, 190 (2021), Suppl 1 / - : Elsevier, 2021, S49-S49

Skup
Toxins Virtual Conference

Mjesto i datum
Online, 16.01.2021. - 17.01.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
botulinum neurotoxin type A ; flaccid paralysis ; muscle atrophy ; muscle hypertonia ; tetanus neurotoxin

Sažetak
Introduction and Objectives: Long-term effects of botulinum neurotoxin type A (BoNT-A) are the basis of its beneficial effects on neurological disorders characterized by muscle hyperactivity, such as spasticity and dystonias. Clinical reports suggest that BoNT-A–mediated normalization of muscle hypertonia does not necessarily correlate with or outlast the duration of muscular flaccid paralysis. The present aim was to reassess these clinical observations in a preclinical model of muscle hypertonia by characterizing the duration of toxin anti-spastic activity in relation to the duration of its muscular effects. Methods: In male Wistar rats, the muscle hypertonia was evoked by tetanus neurotoxin (TeNT) injection into the gastrocnemius (1.75-2 ng total dose). After the development of spastic hypertonia, BoNT-A was similarly injected into the ipsilateral gastrocnemius muscle 7 days post-TeNT (1, 2 and 5 U/kg//20 µL). The effects of TeNT and BoNT-A were further examined by measurements of resistance to passive ankle dorsiflexion, digit abduction score (DAS), and Basso-Beattie-Bresnahan (BBB) Locomotor Rating Scale. Muscle atrophy was quantified by measurement of the medio-lateral calf diameter. After complete recovery of BoNT-A– mediated peripheral flaccid paralysis, the animals were re- injected with TeNT (day 49 after BoNT-A injection) and assessed behaviorally for another 19 days. Results: In the immediate period following the first TeNT injection, all BoNT-A doses employed exhibited a similar reduction of the muscle hypertonia. The TeNT-evoked muscle hypertonia ended by day 28 post-TeNT, while the remaining BoNT-A–mediated flaccid paralysis recovered in a dose-dependent manner by day 42 post–BoNT-A. After the second TeNT injection, the anti-spastic activity of BoNT-A was still present up to day 68 ; however, it was less prominent in rats injected with the lowest BoNT-A (1 U/kg) dose. The level of persisting muscle atrophy, which did not show signs of recovery by the end of the experiment, was similar at all doses employed. Conclusions: In line with clinical reports, we found that the antispastic effect of BoNT-A in rats persists after the lower limb recovery from flaccid paralysis in a dose-dependent manner. Long-term actions of BoNT-A on muscle hypertonia might be mediated by a mechanism distinct from its local muscular paralytic action.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA