Naslov
DARE WE LOOK BEYOND MUSCULAR EFFECTS; LASTING CENTRAL ACTION OF BOTULINUM TOXIN RISING US TO POSSIBLE CLINICAL IMPLICATIONS?

Autori
Šoštarić, Petra ; Matić, Magdalena ; Matak, Ivica

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

Izvornik
19th International Medical Postgraduate Conference Book of Abstract / - , 2022, 71-71

Skup
19th International Medical Postgraduate Conference

Mjesto i datum
Hradec Králové, Češka Republika, 24.11.2022. - 25.11.2022

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
BoNT-A, anticholinergic, presynaptic,

Sažetak
Introduction: Botulinum toxin type A (BoNT-A) is a potent neurotoxin with anticholinergic effect. It is a standard therapy in various movement disorders, presumably due to action on local neuromuscular terminals. However, clinical findings and recent experimental data, points to the possible central effects. Moreover, BoNT-A non- local actions have been reported after BoNT-A treatments as effects on distant muscles located far from treated neuromuscular junctions or muscle spindle zone. Herein, after toxin's peripheral injection, the aim was to examine the contribution of the transcytosis-dependent central toxin action, on normal tone muscle function and recovery, as well as tetanus neurotoxin (TeNT) evoked spasticity Methods: Rats were bilaterally injected with BoNT- A into the gastrocnemius muscle (2 U/kg) or sciatic nerve (5 U/kg). To stop the toxin central transcytosis, BoNT-A-neutralizing antitoxin was intrathecally (i.t.) administered after 24 hours. After recovery from flaccid paralysis, TeNT was intramuscularly (i.m.) injected to animals on day 62, and animals were followed for next 14 days, until they recovered from evoked spastic paralysis. Results: In different motor tests (gait ability score, digit abduction score, rota-rod, beam walking, catwalk), i.t. antitoxin significantly accelerated the flaccid paralysis and motor performance recovery. TeNT-evoked increase in muscle tone was reduced by BoNT-A dependently on its central effect. However, the H-reflex, when corrected for reduced muscle size or reduced compound muscle action potential (CMAP), was not affected by the toxin treatment, suggestive of the lack of the toxin’s direct effect on monosynaptic reflex. The toxin enzymatic activity examined by cleaved synaptosomalassociated protein 25 (cSNAP-25) immunohistochemistry, was still present in neuromuscular junctions and spinal cord. cSNAP-25, presence in second order spinal cord cholinergic neurons, depended on the toxin’s central transcytosis. Conclusion: Long term motor effects of BoNT-A both on normal motor performance (day 1-62), as well as the spastic paralysis (days 62-78), are influenced by the toxin’s ongoing central action mediated by retrograde transport and transcytosis. These data suggest that clinically relevant beneficial effect of BoNT-A result from toxin’s combined peripheral and central effects.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

Napomena
Funding: Croatian Science Foundation (project ID:
UIP-2019-04-8277)

POVEZANOST RADA