Research ReportIntrastriatal injection of botulinum neurotoxin-A is not cytotoxic in rat brain - A histological and stereological analysis

•In rats intrastriatal BoNT-A (1 ng) injections was performed unilaterally.•We counted striatal cholinergic interneurons up to year after BoNT-A.•Intrastriatal BoNT-A injection cause no loss of cholinergic interneurons.•Cholinergic and catecholaminergic BoNT induced varicosities (BiVs) were quantified.•BiV numbers decreases, BiV volumes increases over time after BoNT injection.

Parkinson׳s disease (PD) is caused by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in a deficiency of dopamine in the striatum and an increased release of acetylcholine by tonically active interneurons. Botulinum neurotoxin-A (BoNT-A) is well known for blocking transmitter release by cholinergic presynaptic terminals.Treating striatal hypercholinism by local application of BoNT-A could be a possible new local therapy option of PD. In previous studies of our group, we analyzed the effect of BoNT-A injection into the CPu of 6-OHDA lesioned hemiparkinsonian rats. Our studies showed that BoNT-A application in hemiparkinson rat model is capable of abolishing apomorphine induced rotations for approximately 3 months. Regularly occurring axonal swellings in the BoNT-A infiltrated striata were also discovered, which we named BoNT-A induced varicosities (BiVs).Résumé: Here we investigated the long-term effect of the injection of 1 ng BoNT-A into the right CPu of naive Wistar rats on the number of ChAT-ir interneurons as well as on the numeric density and the volumetric size of the BiVs in the CPu. Significant differences in the number of ChAT-ir neurons between the right BoNT-A treated CPu and the left untreated CPu were not detected up to 12 month post BoNT-A injection. The numeric density of BiVs in the treated CPu reached a maximum 3 months after BoNT-A treatment and decreased afterwards, whereas the volume of single BiVs increased steadily throughout the whole time course of the experiment.