scholarly journals Botulinum Neurotoxin-A Injected Intrastriatally into Hemiparkinsonian Rats Improves the Initiation Time for Left and Right Forelimbs in Both Forehand and Backhand Directions

2019 ◽  
Vol 20 (4) ◽  
pp. 992 ◽  
Author(s):  
Veronica Antipova ◽  
Carsten Holzmann ◽  
Alexander Hawlitschka ◽  
Andreas Wree
Keyword(s):  
Beneficial Effect ◽  
Survival Time ◽  
Botulinum Neurotoxin ◽  
Test Procedure ◽  
Initiation Time ◽  
Classical Approach ◽  
Botulinum Neurotoxin A ◽  
Simple Method ◽  
Ipsilateral Striatum ◽  
Left And Right

Forelimb stepping is a widely used test for the assessment of forelimb akinesia in hemiparkinsonian (hemi-PD) rats. The initiation time (IT) is considered the most sensitive parameter in the stepping test procedure. Here we propose a novel, reliable, and simple method for the measurement of IT of both forelimbs in both forehand and backhand directions in rats. Evaluating the same videos taken for quantifying adjusting steps, IT measurements were done without additional experiments. This is in contrast to the classical approach introduced by Olsson et al. (1995), in which separate experiments are necessary. We successfully applied our approach to hemi-PD rats intrastriatally treated with botulinum neurotoxin-A (BoNT-A). In naïve rats, an IT of about 0.62 s was found, and in right-sided hemi-PD rats the IT of the left forepaw increased to about 3.62 s. These hemi-PD rats showed, however, reduced ITs of the impaired left forepaws 1 month and the second time 7 months after induction of hemi-PD via the injection of 1 ng BoNT-A into the ipsilateral striatum, depending on post BoNT-A survival time. The method described offers the possibility of a precise and animal-friendly evaluation of IT in rats, including the beneficial effect of BoNT-A treatment in hemi-PD rats.

scholarly journals Repeated Intrastriatal Botulinum Neurotoxin-A Injection in Hemiparkinsonian Rats Increased the Beneficial Effect on Rotational Behavior

Toxins ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 368 ◽  
Author(s):  
Alexander Hawlitschka ◽  
Carsten Holzmann ◽  
Andreas Wree ◽  
Veronica Antipova
Keyword(s):  
Beneficial Effect ◽  
Rotation Rate ◽  
Botulinum Neurotoxin ◽  
Acetylcholinesterase Inhibitor ◽  
Rotational Behavior ◽  
Motor Symptoms ◽  
Botulinum Neurotoxin A ◽  
Motor Behaviors

Injection of botulinum neurotoxin-A (BoNT-A) into the striatum of hemiparkinsonian (hemi-PD) rats reduced apomorphine-induced rotation behavior significantly, for at least 3 months. Thereafter, rotation behavior increased again. We injected hemi-PD rats with 1 ng BoNT-A twice, the second injection following 6 months after the first one and tested the rats for apomorphine-induced rotations and spontaneous motor behaviors, i.e., corridor task and stepping test. To test the hypothesis that BoNT-A reduced striatal hypercholinism in hemi-PD rats, the acetylcholinesterase inhibitor donepezil was injected prior to separate apomorphine-induced rotation tests. In hemi-PD rats, the first BoNT-A injection led to a clear reduction of the apomorphine-induced rotations, and the second BoNT-A injection to a more massive and prolonged reaction. In hemi-PD rats whose apomorphine-induced rotation behavior was strongly reduced by an intrastriatal BoNT-A, subsequent donepezil injections led to significant increases of the rotation rate. Concerning corridor task and stepping test, neither first nor second BoNT-A injections changed hemi-PD rats’ behavior significantly. The data give evidence for the possibility of repeated intrastriatal administrations of BoNT-A, for treatment of motor symptoms in experimental hemi-PD over a longer time.

Identification of novel inhibitors of botulinum neurotoxin A

Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
C Yalamanchili ◽  
VK Manda ◽  
AG Chittiboyina ◽  
WA Harrell Jr ◽  
RP Webb ◽  
...  
Keyword(s):  
Botulinum Neurotoxin ◽  
Botulinum Neurotoxin A

Botulinumtoxin zur Behandlung von neuropathischen Schmerzen

2017 ◽  
Vol 36 (05) ◽  
pp. 315-323
Author(s):  
N. Üçeyler ◽  
C. Sommer
Keyword(s):  
Botulinum Neurotoxin ◽  
Neuropathische Schmerzen ◽  
Botulinum Neurotoxin A ◽  
Topische Therapien

ZusammenfassungDie Behandlung neuropathischer Schmerzen mit systemisch wirksamen oral verabreichten Pharmaka ist bei vielen Patienten wirksam, kann jedoch zu zentralnervösen unerwünschten Wirkungen wie Müdigkeit oder Schwindel führen. Daher sind in den letzten Jahren topische Therapien in das Zentrum der Aufmerksamkeit gerückt. Botulinumtoxin, etabliert in der Therapie von Dystonien und Spastik, wurde zunehmend bei Schmerzerkrankungen getestet, hierbei ist Botulinum-Neurotoxin A der am besten untersuchte Serotyp. Die häufigsten Indikationen waren Schmerzen im Trigeminusversorgungsbereich und periphere neuropathische Schmerzen. Bei den meisten Studien war Botulinum-Neurotoxin A Placebo deutlich überlegen. Präklinische Studien zum Wirkmechanismus erbrachten die Erkenntnis, dass neben dem erwarteten peripheren Effekt sehr wahrscheinlich auch eine zentrale Reduktion der Ausschüttung von exzitatorischen Neurotransmittern an der Wirkung beteiligt ist.

scholarly journals Primary Cultures of Embryonic Chicken Neurons for Sensitive Cell-Based Assay of Botulinum Neurotoxin: Implications for Therapeutic Discovery

2007 ◽  
Vol 12 (3) ◽  
pp. 370-377 ◽  
Author(s):  
Andrea M. Stahl ◽  
Gordon Ruthel ◽  
Edna Torres-Melendez ◽  
Tara A. Kenny ◽  
Rekha G. Panchal ◽  
...  
Keyword(s):  
Nervous System ◽  
Botulinum Toxin ◽  
Neutralizing Antibodies ◽  
Botulinum Neurotoxin ◽  
Potent Inhibitor ◽  
Primary Cultures ◽  
Embryonic Chick ◽  
Sensitive Cell ◽  
Botulinum Neurotoxin A ◽  
Therapeutic Compounds

Botulinum toxin is an exceedingly potent inhibitor of neurotransmission across the neuromuscular junction, causing flaccid paralysis and death. The potential for misuse of this deadly poison as a bioweapon has added a greater urgency to the search for effective therapeutics. The development of sensitive and efficient cell-based assays for the evaluation of toxin antagonists is crucial to the rapid and successful identification of therapeutic compounds. The authors evaluated the sensitivity of primary cultures from 4 distinct regions of the embryonic chick nervous system to botulinum neurotoxin A (BoNT/A) cleavage of synaptosomal-associated protein of 25 kD (SNAP-25). Although differences in sensitivity were apparent, SNAP-25 cleavage was detectable in neuronal cells from each of the 4 regions within 3 h at BoNT/A concentrations of 1 nM or lower. Co-incubation of chick neurons with BoNT/A and toxin-neutralizing antibodies inhibited SNAP-25 cleavage, demonstrating the utility of these cultures for the assay of BoNT/A antagonists. ( Journal of Biomolecular Screening 2007:370-377)

scholarly journals Intratracheal inoculation of AHc vaccine induces protection against aerosolized botulinum neurotoxin A challenge in mice

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Changjiao Gan ◽  
Wenbo Luo ◽  
Yunzhou Yu ◽  
Zhouguang Jiao ◽  
Sha Li ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Clostridium Botulinum ◽  
Freeze Drying ◽  
Botulinum Neurotoxin ◽  
Secretory Iga ◽  
Immune Protection ◽  
Dry Powder ◽  
Botulinum Neurotoxin A ◽  
Spray Freeze Drying

AbstractBotulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.) inoculation immunization with recombinant Hc subunit (AHc) vaccines against aerosolized BoNT/A intoxication. Three AHc vaccine formulations, i.e., conventional liquid, dry powder produced by spray freeze drying, and AHc dry powder reconstituted in water are prepared, and mice are immunized via i.t. inoculation or subcutaneous (s.c.) injection. Compared with s.c.-AHc-immunized mice, i.t.-AHc-immunized mice exhibit a slightly stronger protection against a challenge with 30,000× LD50 aerosolized BoNT/A. Of note, only i.t.-AHc induces a significantly higher level of toxin-neutralizing mucosal secretory IgA (SIgA) production in the bronchoalveolar lavage of mice. In conclusion, our study demonstrates that the immune protection conferred by the three formulations of AHc is comparable, while i.t. immunization of AHc is superior to s.c. immunization against aerosolized BoNT/A intoxication.

scholarly journals Strategies to Counteract Botulinum Neurotoxin A: Nature’s Deadliest Biomolecule

2019 ◽  
Vol 52 (8) ◽  
pp. 2322-2331 ◽  
Author(s):  
Lucy Lin ◽  
Margaret E. Olson ◽  
Lisa M. Eubanks ◽  
Kim D. Janda
Keyword(s):  
Botulinum Neurotoxin ◽  
Botulinum Neurotoxin A

Covalent inhibition of botulinum neurotoxin A – Exploration of warhead reactivity and function using a bifunctional approach

Toxicon ◽  
2021 ◽  
Vol 190 ◽  
pp. S72-S73
Author(s):  
Lewis D. Turner ◽  
Alexander L. Nielsen ◽  
Lucy Lin ◽  
Sabine Pellett ◽  
Takashi Sugane ◽  
...  
Keyword(s):  
Botulinum Neurotoxin ◽  
Botulinum Neurotoxin A ◽  
Covalent Inhibition ◽  
And Function

Septal injection of botulinum neurotoxin A for idiopathic rhinitis: a pilot study

2012 ◽  
Vol 33 (1) ◽  
pp. 64-67 ◽  
Author(s):  
Thomas Braun ◽  
Robert Gürkov ◽  
Matthias F. Kramer ◽  
Eike Krause
Keyword(s):  
Pilot Study ◽  
Botulinum Neurotoxin ◽  
Botulinum Neurotoxin A ◽  
Idiopathic Rhinitis
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