{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:27:58Z","timestamp":1787610478518,"version":"build-2736575974"},"reference-count":74,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Croatian Research Foundation","award":["HRZZ UIP-2019-04-8277"],"award-info":[{"award-number":["HRZZ UIP-2019-04-8277"]}]},{"name":"Croatian Research Foundation","award":["DOK-2021-02-6169"],"award-info":[{"award-number":["DOK-2021-02-6169"]}]},{"name":"FarmInova","award":["KK.01.1.1.02.0021"],"award-info":[{"award-number":["KK.01.1.1.02.0021"]}]},{"name":"European Regional Development Fund, Operational Program Competitiveness and Cohesion"},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>We previously demonstrated that botulinum neurotoxin A (BoNT-A) exerts bilateral antinociceptive effects, involving trans-synaptic transport at the level of the lumbar spinal cord. However, the potential distribution of the toxin to supraspinal sites has not yet been investigated. In the present study, we examined the distribution of cleaved SNAP-25 (cl-SNAP-25), a marker of BoNT-A activity, in the rat brain following peripheral unilateral BoNT-A administration. Brain tissues from rats treated with BoNT-A (7 U\/kg, into the hind paw) were analyzed using immunofluorescent tyramide signal amplification to detect cl-SNAP-25. To assess the contribution of trans-synaptic transport, a BoNT-A-neutralizing antitoxin (2 IU) was administered intrathecally 24 h after BoNT-A injection. Signal intensity was evaluated using a semi-quantitative immunohistochemical scoring method based on cl-SNAP-25-positive nerve fibers. Bilateral cl-SNAP-25 immunoreactivity was observed in multiple supraspinal regions, most prominently within the trigeminal complex and the facial and gracile nuclei. Signal intensity was significantly reduced by intrathecal antitoxin, indicating that trans-synaptic transport contributes to central BoNT-A distribution. Peripherally administered BoNT-A reaches distant supraspinal regions, possibly via neuronal retrograde and trans-synaptic transport. Further studies are warranted to clarify exact pathways and alternative distribution routes, determine the functional relevance of central BoNT-A presence, and assess its clinical implications.<\/jats:p>","DOI":"10.3390\/toxins18060261","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:58:12Z","timestamp":1781053092000},"page":"261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Regional Brain Localization of Botulinum Toxin Type A-Truncated Synaptosomal-Associated Protein 25 After Injection into the Rat Hind Paw"],"prefix":"10.3390","volume":"18","author":[{"given":"Dalia","family":"Nemani\u0107","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Zagreb, Faculty of Pharmacy and Biochemistry, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3491-0537","authenticated-orcid":false,"given":"Mihael","family":"Grdunac","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Zagreb, Faculty of Pharmacy and Biochemistry, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6521-4948","authenticated-orcid":false,"given":"Petra \u0160o\u0161tari\u0107","family":"Mu\u017ei\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Karolinska Institutet, Solnavagen 9, Kvarter B4, 17165 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7016-1853","authenticated-orcid":false,"given":"Patrik","family":"Megli\u0107","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuropharmacology, Department of Pharmacology, Croatian Institute of Brain Research, University of Zagreb, School of Medicine, \u0160alata 11, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivica","family":"Matak","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuropharmacology, Department of Pharmacology, Croatian Institute of Brain Research, University of Zagreb, School of Medicine, \u0160alata 11, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4580-833X","authenticated-orcid":false,"given":"Lidija","family":"Bach-Rojecky","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Zagreb, Faculty of Pharmacy and Biochemistry, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rossetto, O., and Montecucco, C. (2019). Tables of Toxicity of Botulinum and Tetanus Neurotoxins. Toxins, 11.","DOI":"10.3390\/toxins11120686"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1124\/pr.116.012658","article-title":"Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology","volume":"69","author":"Pirazzini","year":"2017","journal-title":"Pharmacol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Luvisetto, S. (2021). Botulinum Neurotoxins in Central Nervous System: An Overview from Animal Models to Human Therapy. 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