Centralni učinci botulinum toksina tipa A na neurotransmitere i neuronalne markere u kralježničnoj moždini štakora s lokalnim mišićnim spasticitetom

master's thesis

• Title (english): Central effects of botulinum toxin type A on spinal cord neurotransmitters and inhibitory neuron markers in rats with local muscular spasticity
• Author: Mislav Barišić-Jaman
• Mentor: Ivica Matak (mentor)
• Committee member: VLADIMIR TRKULJA (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Ivica Matak (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pharmacology); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology

Abstract

Botulinum toksin tip A jedan je od najšire primjenjivanih lijekova u liječenju lokalnih mišićnih hiperkinetičkih poremećaja. Nedavna istraživanja su pokazala mogući terapijski učinak djelovanja BoNT/A na razini centralnih motoneuorna. U ovom radu želimo ispitati ovu hipotezu istražujući učinke BoNT/A na centralnu neurotransmisiju i neuronalne proteinske markere po prvi puta koristeći štakorski model fokalne mišićne hipertonije u istraživanju njegova djelovanja. Štakori su podijeljeni u četiri grupe: kontrolna (vehikulum+fiziološka otopina), TeNT+fiziološka otopina, vehikulum+BoNT/A i TeNT+BoNT/A. Unilateralni mišićni spazam induciran je niskom dozom TeNT im. Farmakološki odgovor na im. i in. injekciju BoNT/A je zabilježen različitim motoričkim parametrima i testovima u svjesnih životinja. Kralježnična moždina štakora je analizirana na koncentracije glutamata i GABA-e ELISA metodom, a ekspresija VAMP-2, SV2C, CGRP i NeuN imunohistokemijski. Rezultati bihevioralnih testova su pokazali da BoNT/A primijenjen i in. i im. smanjuje hipertoniju mišića. Mjerenjem ukupne koncentracije GABA-e i glutamata u tkivu ventralnog roga nije bilo moguće utvrditi potencijalno djelovanje BoNT/A na disbalans inhibicijske i ekscitacijske transmisije. U ventralnom je rogu detektiran pocijepani SNAP-25 nakon primjene BoNT/A i u mišić i u živac, što ukazuje na njegovo moguće centralno djelovanje. Međutim, objašnjenje antispastičkog djelovanja BoNT/A u središnjem živčanom sustavu zahtijeva daljnja istraživanja.

Abstract (english)

Botulinum toxin type A is one of the most widely used drugs in the treatment of local muscular hyperkinetic disorders. Recent studies have demonstrated the possible therapeutic effect of BoNT/A on the central motoneurons. In this paper we want to examine this hypothesis by investigating the effects of BoNT/A on central neurotransmission and neuronal protein markers using a rat model of focal muscle hypertonia. The rats were divided into four groups: control (vehicle + saline), TeNT + saline, vehicle + BoNT/A and TeNT + BoNT/A. Unilateral muscle spasm was induced by a low intramuscular dose of TeNT. The rat spinal cord was analyzed on glutamate and GABA concentrations by ELISA. The expression of VAMP-2, SV2C, CGRP and NeuN proteins was analyzed immunohistochemically. The results of behavioral tests have shown that BoNT/A applied by intraneural and intramuscular route reduces muscle hypertonia. By measuring the total concentration of GABA and glutamate in ventral horn, it was not possible to determine the potential effect of BoNT/A on the inhibitory and excitatory transmission mismatch. In the ventral horn, cleaved SNAP-25 was detected after administration of BoNT/A in muscle and nerve, indicating its possible central activity. However, an explanation of the antispastic effect of BoNT/A in the central nervous system requires further research.

• Keywords: botulinum toksin tip A; tetanus toksin; kralježnična moždina; mišićni spazam; hiperkinetički poremećaji pokreta
• Keywords (english): botulinum toxin type A; tetanus toxin; spinal cord; muscular spasticity; hyperkinetic movement disorders
• Language: croatian
• URN:NBN: urn:nbn:hr:105:200600
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-10-30 10:08:12