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Regional anatomy teaching forms a cornerstone of undergraduate medical education. Owing to an increase in teaching and learning content throughout the medical curriculum in recent years, contact hours and overall course durations in anatomy are under review worldwide. This study aimed to assess whether shortening the course content duration impacts learning gain and the ability to identify anatomical structures correctly. Undergraduate medical students of the Johannes Kepler University Linz (JKU; n = 310) and at the Medical University of Graz (MUG; n = 156) participating in regional anatomy courses were included. Whole body regional anatomy courses, including hands-on dissection and accompanying lectures, were delivered over one or three months. Course content and examination mode were kept consistent, while the duration of knowledge delivery was one or three months, respectively. Objective structured practical examinations (OSPE) were then carried out on prosections for the neck, thorax, and abdomen. 3-month course exposure resulted in significantly higher OSPE scores for the neck (49 vs. 37%), thorax (65 vs. 54%), and abdomen (65 vs. 45%), respectively. Further evaluation of the utility of different embalming types yielded higher 3-month scores in the neck and thorax regions with Thiel-embalmed tissues and thorax and abdomen regions in ethanol-glycerin-embalmed tissues. Course exposure over a more extended period, like three months, appears to be highly beneficial.
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Background and Objectives: Facial vascular anatomy plays a pivotal role in both physiological context and in surgical intervention. While data exist on the individual course of the facial artery and vein, to date, the spatial relationship of the vasculature has been ill studied. The aim of this study was to assess the course of facial arteries, veins and branches one relative to another. Materials and Methods: In a total of 90 halved viscerocrania, the facial vessels were injected with colored latex. Dissection was carried out, the relation of the facial vessels was studied, and the distance at the lower margin of the mandible was measured. Furthermore, branches including the labial and angular vessels were assessed. Results: At the base of the mandible, the facial artery was located anterior to the facial vein in all cases at a mean distance of 6.2 mm (range 0-15 mm), with three cases of both vessels adjacent. An angular vein was present in all cases, while an angular artery was only present in 34.4% of cases. Conclusions: The main trunk of the facial artery and vein yields a rather independent course, with the facial artery always located anterior to the vein, while their branches, especially the labial vessels, demonstrate a closer relationship.
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Cadáver , Face , Humanos , Face/irrigação sanguínea , Face/anatomia & histologia , Masculino , Feminino , Artérias/anatomia & histologia , Veias/anatomia & histologia , Mandíbula/anatomia & histologia , Mandíbula/irrigação sanguíneaRESUMO
Background and Objectives: The facial vein is the main collector of venous blood from the face. It plays an important role in physiological as well as pathological context. However, to date, only limited data on the course and tributaries of the facial vein are present in contemporary literature. The aim of this study was to provide detail on the course and the tributaries of the facial vein. Materials and Methods: In 96 sides of 53 body donors, latex was injected into the facial vein. Dissection was carried out and the facial vein and its tributaries (angular vein, ophthalmic vein, nasal veins, labial veins, palpebral veins, buccal and masseteric veins) were assessed. Results: The facial vein presented a textbook-like course in all cases and crossed the margin of the mandible anterior to the masseter in 6.8% of cases, while being located deep to the zygomaticus major muscle in all cases and deep to the zygomaticus minor in 94.6% of cases. Conclusions: This work offers detailed information on the course of the facial vein in relation to neighboring structures, which shows a relatively consistent pattern, as well as on its tributaries, which show a high variability.
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Face , Veias Jugulares , Humanos , Mandíbula , Músculo Masseter , NarizRESUMO
Background and Objectives: Anastomoses of the extracranial and intracranial venous system have been described in the literature. The presence of such anastomoses may facilitate a possible spread of infection into the dural venous sinuses. However, the frequency and relevance of such anastomoses is highly debated. The aim of this study was to quantify frequencies of anastomoses between the facial vein and the dural venous sinuses. Materials and Methods: In 32 sides of 16 specimens, latex was injected into the facial vein. Dissection was carried out to follow and described these anastomoses, yielding the presence of latex in the intracranial venous system. Results: In 97% of cases, a dispersal of latex into the cavernous sinus as well as anastomoses was observed. A further dispersal of latex into other dural venous sinuses was found at rates ranging between 34% (transverse sinus)-88% (superior petrosal sinus), respectively. Conclusions: The presence of anastomoses between the extracranial and intracranial venous system in a majority of cases needs to be considered when dealing with pathologies as well as procedures in the facial region.
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Seio Cavernoso , Látex , Humanos , Cavidades Cranianas/patologia , Veias Jugulares , FaceRESUMO
Niemann-Pick Type C1 (NPC1, MIM 257220) is a rare, progressive, lethal, inherited autosomal-recessive endolysosomal storage disease caused by mutations in the NPC1 leading to intracellular lipid storage. We analyzed mostly not jet known alterations of the weights of 14 different organs in the BALB/cNctr-Npc1m1N/-J Jackson Npc1 mice in female and male Npc1+/+ and Npc1-/- mice under various treatment strategies. Mice were treated with (i) no therapy, (ii) vehicle injection, (iii) a combination of miglustat, allopregnanolone, and 2-hydroxypropyl-ß-cyclodextrin (HPßCD), (iv) miglustat, and (v) HPßCD alone starting at P7 and repeated weekly throughout life. The 12 respective male and female wild-type mice groups were evaluated in parallel. In total, 351 mice (176 Npc1+/+, 175 Npc1-/-) were dissected at P65. In both sexes, the body weights of None and Sham Npc1-/- mice were lower than those of respective Npc1+/+ mice. The influence of the Npc1 mutation and/or sex on the weights of various organs, however, differed considerably. In males, Npc1+/+ and Npc1-/- mice had comparable absolute weights of lungs, spleen, and adrenal glands. In Npc1-/- mice, smaller weights of hearts, livers, kidneys, testes, vesicular, and scent glands were found. In female Npc1-/- mice, ovaries, and uteri were significantly smaller. In Npc1-/- mice, relative organ weights, i.e., normalized with body weights, were sex-specifically altered to different extents by the different therapies. The combination of miglustat, allopregnanolone, and the sterol chelator HPßCD partly normalized the weights of more organs than miglustat or HPßCD mono-therapies.
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1-Desoxinojirimicina , Ciclodextrinas , Tamanho do Órgão , Pregnanolona , Animais , Feminino , Masculino , Camundongos , 1-Desoxinojirimicina/farmacologia , Peso Corporal , Ciclodextrinas/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Proteína C1 de Niemann-Pick , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Doença de Niemann-Pick Tipo C/genética , Pregnanolona/farmacologia , Camundongos KnockoutRESUMO
Background. For neurodegenerative diseases such as Huntington's disease (HD), early diagnosis is essential to treat patients and delay symptoms. Impaired olfaction, as observed as an early symptom in Parkinson´s disease, may also constitute a key symptom in HD. However, there are few reports on olfactory deficits in HD. Therefore, we aimed to investigate, in a transgenic rat model of HD: (1) whether general olfactory impairment exists and (2) whether there are disease-specific dynamics of olfactory dysfunction when the vomeronasal (VNE) and main olfactory epithelium (MOE) are compared. Methods. We used male rats of transgenic line 22 (TG22) of the bacterial artificial chromosome Huntington disease model (BACHD), aged 3 days or 6 months. Cell proliferation, apoptosis and macrophage activity were examined with immunohistochemistry in the VNE and MOE. Results. No differences were observed in cellular parameters in the VNE between the groups. However, the MOE of the 6-month-old HD animals showed a significantly increased number of mature olfactory receptor neurons. Other cellular parameters were not affected. Conclusions. The results obtained in the TG22 line suggest a relative stability in the VNE, whereas the MOE seems at least temporarily affected.
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Doença de Huntington , Transtornos do Olfato , Neurônios Receptores Olfatórios , Animais , Cromossomos Artificiais Bacterianos , Modelos Animais de Doenças , Doença de Huntington/metabolismo , Masculino , Transtornos do Olfato/metabolismo , Mucosa Olfatória/metabolismo , Neurônios Receptores Olfatórios/metabolismo , Ratos , Ratos TransgênicosRESUMO
In a mouse model of Niemann-Pick disease type C1 (NPC1), a combination therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-ß-cyclodextrin (HPßCD) has previously resulted in, among other things, significantly improved motor function. The present study was designed to compare the therapeutic effects of the COMBI therapy with that of MIGLU or HPßCD alone on body and brain weight and the behavior of NPC1-/- mice in a larger cohort, with special reference to gender differences. A total of 117 NPC1-/- and 123 NPC1+/+ mice underwent either COMBI, MIGLU only, HPßCD only, or vehicle treatment (Sham), or received no treatment at all (None). In male and female NPC1-/- mice, all treatments led to decreased loss of body weight and, partly, brain weight. Concerning motor coordination, as revealed by the accelerod test, male NPC1-/- mice benefited from COMBI treatment, whereas female mice benefited from COMBI, MIGLU, and HPßCD treatment. As seen in the open field test, the reduced locomotor activity of male and female NPC1-/- mice was not significantly ameliorated in either treatment group. Our results suggest that in NPC1-/- mice, each drug treatment scheme had a beneficial effect on at least some of the parameters evaluated compared with Sham-treated mice. Only in COMBI-treated male and female NPC+/+ mice were drug effects seen in reduced body and brain weights. Upon COMBI treatment, the increased dosage of drugs necessary for anesthesia in Sham-treated male and female NPC1-/- mice was almost completely reduced only in the female groups.
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1-Desoxinojirimicina/análogos & derivados , 2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Doença de Niemann-Pick Tipo C/tratamento farmacológico , 1-Desoxinojirimicina/farmacologia , Animais , Ciclodextrinas/farmacologia , Modelos Animais de Doenças , Quimioterapia Combinada/métodos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pregnanolona/farmacologiaRESUMO
Background and Objectives: Vascular variations appear as morphologically distinct patterns of blood diverging from the most commonly observed vessel patterns. The facial artery is considered to be the main vessel for supplying blood to the anterior part of the face. An anatomical understanding of the facial artery, its course, its topography, and its branches is important in medical and dental practice (especially in neck and face surgery), and is also essential for radiologists to be able to interpret vascular imaging in the face following angiography of the region. A profound knowledge of the arteries in the region will aid in minimizing the risks to the patient. Materials and Methods: In our publication a narrative literature review and a case report are presented. Results: A rare case of a facial artery pattern has been described anatomically for the first time with respect to its course and branching. This variation was found on the left side of a 60-year-old male corpse during anatomical dissection. The anterior branch of the facial artery arched in the direction of the labial angle, and there divided into the inferior and superior labial arteries. At the same time, the posterior branch coursed vertically and superficially to the masseter muscle. It here gave off the premasseteric branch, and continued towards the nose, where it ran below the levator labii superioris and the levator labii superioris alaeque nasi muscles and terminated at the dorsum nasi. Conclusions: Our review of the literature and the case report add to knowledge on the facial artery with respect to its topographical anatomy and its branching and termination patterns, as well as the areas of supply. An exact knowledge of individual facial artery anatomy may play an important role in the planning of flaps or tumor excisions due to the differing vascularization and can also help to prevent artery injuries during aesthetic procedures such as filler and botulinum toxin injections.
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Artérias , Face , Artérias/diagnóstico por imagem , Cadáver , Face/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Nariz , Retalhos CirúrgicosRESUMO
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.
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Toxinas Botulínicas Tipo A/administração & dosagem , Corpo Estriado/efeitos dos fármacos , Membro Anterior/inervação , Atividade Motora/efeitos dos fármacos , Transtornos Parkinsonianos/terapia , Animais , Toxinas Botulínicas Tipo A/farmacologia , Modelos Animais de Doenças , Injeções , Masculino , Ratos , Ratos WistarRESUMO
Background: Niemann-Pick disease type C1 (NPC1, MIM 257220) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of Npc1-/- displays a rapidly progressing form of Npc1 disease, which is characterized by weight loss, ataxia, and increased cholesterol storage. Npc1-/- mice receiving a combined therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-ß-cyclodextrin (HPßCD) showed prevention of Purkinje cell loss, improved motor function and reduced intracellular lipid storage. Although therapy of Npc1-/- mice with COMBI, MIGLU or HPßCD resulted in the prevention of body weight loss, reduced total brain weight was not positively influenced. Methods: In order to evaluate alterations of different brain areas caused by pharmacotherapy, fresh volumes (volumes calculated from the volumes determined from paraffin embedded brain slices) of various brain structures in sham- and drug-treated wild type and mutant mice were measured using stereological methods. Results: In the wild type mice, the volumes of investigated brain areas were not significantly altered by either therapy. Compared with the respective wild types, fresh volumes of specific brain areas, which were significantly reduced in sham-treated Npc1-/- mice, partly increased after the pharmacotherapies in all treatment strategies; most pronounced differences were found in the CA1 area of the hippocampus and in olfactory structures. Discussion: Volumes of brain areas of Npc1-/- mice were not specifically changed in terms of functionality after administering COMBI, MIGLU, or HPßCD. Measurements of fresh volumes of brain areas in Npc1-/- mice could monitor region-specific changes and response to drug treatment that correlated, in part, with behavioral improvements in this mouse model.
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Botulinum neurotoxin (BoNT) inhibits the release of acetylcholine from presynaptic vesicles through its proteinase activity cleaving the SNARE complex. Parkinson's disease (PD) is associated with locally increased cholinergic activity in the striatum. Therefore, the present study investigates the effect of unilateral intrastriatal BoNT-A injection in naïve rats on striatal morphology; i.e., the total number of Nissl-stained neurons and the volume of caudate-putamen (CPu) were estimated. Furthermore, stainings for markers of gliosis (glial fibrillary acidic protein) and microglia (Iba1) were performed. In addition, the potential beneficial effects of a unilateral intrastriatal injection of BoNT-A on motor activity in the rat model of hemi-PD were evaluated. Hemi-PD was induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle. Six weeks later, rats received an ipsilateral intrastriatal injection of BoNT-A. Behaviorally, motor performance was tested. The total number of CPu neurons and the striatal volume were not significantly different between the BoNT-A-injected right and the intact left hemispheres of naïve rats. In hemi-PD rats, intrastriatal BoNT-A abolished apomorphine-induced rotations, increased amphetamine-induced rotations, and tended to improve left forelimb usage. Forced motor function in the accelerod test was not significantly changed by BoNT-A, and open field activity was also unaltered compared with sham treatment. Thus, intrastriatal BoNT-A affects spontaneous motor activity of hemi-PD rats to a minor degree compared with drug-induced motor function. In the future, tests assessing the cognitive and emotional performance should be performed to ascertain finally the potential therapeutic usefulness of intrastriatal BoNT-A for PD.
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Toxinas Botulínicas Tipo A/administração & dosagem , Corpo Estriado/efeitos dos fármacos , Neurotoxinas/administração & dosagem , Transtornos Parkinsonianos/patologia , Animais , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/patologia , Imuno-Histoquímica , Injeções Intraventriculares , Masculino , Atividade Motora/efeitos dos fármacos , Transtornos Parkinsonianos/fisiopatologia , Ratos , Ratos WistarRESUMO
Digital workflows have become integral in orthodontic diagnosis and therapy, reducing risk factors and chair time with one-visit protocols. This study assessed the transfer accuracy of fully digital planned insertion guides for orthodontic mini-implants (OMIs) compared with freehanded insertion. Cone-beam computed tomography (CBCT) datasets and intraoral surface scans of 32 cadaver maxillae were used to place 64 miniscrews in the anterior palate. Three groups were formed, two using printed insertion guides (A and B) and one with freehand insertion (C). Group A used commercially available customized surgical templates and Group B in-house planned and fabricated insertion guides. Postoperative CBCT datasets were superimposed with the planning model, and accuracy measurements were performed using orthodontic software. Statistical differences were found for transverse angular deviations (4.81° in A vs. 12.66° in B and 5.02° in C, p = 0.003) and sagittal angular deviations (2.26° in A vs. 2.20° in B and 5.34° in C, p = 0.007). However, accurate insertion depth was not achieved in either guide group; Group A insertion was too shallow (-0.17 mm), whereas Group B insertion was deeper (+0.65 mm) than planned. Outsourcing the planning and fabrication of computer-aided design and computer-aided manufacturing insertion guides may be beneficial for certain indications; particularly, in this study, commercial templates demonstrated superior accuracy than our in-house-fabricated insertion guides.
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Technological approaches deploying three-dimensional visualization to integrate virtual anatomy are increasingly used to provide medical students with state-of-the-art teaching. It is unclear to date to which extent virtual anatomy may help replace the dissection course. Medical students of Johannes Kepler University attend both a dissection and a virtual anatomy course. This virtual anatomy course is based on Cinematic Rendering and radiological imaging and teaches anatomy and pathology. This study aims to substantiate student benefits achieved from this merged teaching approach. Following their dissection course, 120 second-year students took part in objective structured practical examinations (OSPE) conducted on human specimens prior to and following a course on Cinematic Rendering virtual anatomy. Likert-based and open-ended surveys were conducted to evaluate student perceptions of both courses and their utility. Virtual anatomy teaching was found to be unrelated to improvements in student's ability to identify anatomical structures in anatomical prosections, yielding only a 1.5% increase in the OSPE score. While the students rated the dissection course as being more important and impactful, the virtual anatomy course helped them display the learning content in a more comprehensible and clinically applicable way. It is likely that Cinematic Rendering-based virtual anatomy affects knowledge gain in domains other than the recognition of anatomical structures in anatomical prosections. These findings underline students' preference for the pedagogic strategy of the dissection course and for blending this classical approach with novel developments like Cinematic Rendering, thus preparing future doctors for their clinical work.
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Anatomia , Estudantes de Medicina , Humanos , Anatomia/educação , Currículo , Dissecação/educação , AprendizagemRESUMO
Anatomical dissection is known to serve as an integral tool in teaching gross anatomy, including postgraduate training. A variety of embalming techniques exist, resulting in different haptic and optical tissue properties. This study aimed to objectify learning outcomes and medical student perceptions related to the use of two widely used embalming techniques, namely Thiel and ethanol-glycerin embalming. Between 2020 and 2022, first- and second-year medical students enrolled in the course on topographic anatomy participated in this study. Objective structured practical examinations were carried out for the head, neck, thorax, abdomen, pelvis, and extremity regions following regional dissection just before the oral examinations began. Six to ten numbered tags were marked in prosections of each region in Thiel- and ethanol-glycerin-embalmed specimens. Following the examinations, the students were surveyed regarding the suitability of the two embalming techniques with respect to preservation, colorfastness, tissue pliability, and the suitability in preparing for their anatomy examinations. Consistently higher scores were achieved for the thoracic and abdominal regions in ethanol-glycerin-embalmed specimens when compared to Thiel. No benefit was found for Thiel-embalmed upper or lower extremities. Tissues embalmed with ethanol-glycerin were rated higher for preservation and suitability to achieve the learning objectives, tissue pliability was rated higher for Thiel-embalmed tissues. Ethanol-glycerin embalming appears to offer certain advantages for undergraduate students in recognizing visceral structures, which may align with students' ideas on tissue suitability for their learning. Consequently, the benefits reported for Thiel embalming for postgraduate study unlikely reflect its suitability for novices.
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Anatomia , Estudantes de Medicina , Humanos , Glicerol , Etanol , Embalsamamento/métodos , Anatomia/educação , CadáverRESUMO
Olfactory deficits occur as early non-motor symptoms of idiopathic Parkinson's disease (PD) in humans. The first central relay of the olfactory pathway, the olfactory bulb (OB), depends, among other things, on an intact, functional crosstalk between dopaminergic interneurons and dopamine receptors (D2/D3R). In rats, hemiparkinsonism (hemi-PD) can be induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB), disrupting dopaminergic neurons of the substantia nigra pars compacta (SNpc). In a previous study, we showed that subsequent injection of botulinum neurotoxin-A (BoNT-A) into the striatum can reverse most of the pathological motor symptoms and normalize the D2/D3R availability. To determine whether this rat model is suitable to explain olfactory deficits that occur in humans with PD, we examined the availability of D2/D3R by longitudinal [18F]fallypride-PET/CT, the density of tyrosine hydroxylase immunoreactivity in the OB, olfactory performance by an orienting odor identification test adapted for rats, and a connectome analysis. PET/CT and immunohistochemical data remained largely unchanged after 6-OHDA lesion in experimental animals, suggesting that outcomes of the 6-OHDA hemi-PD rat model do not completely explain olfactory deficits in humans. However, after subsequent ipsilateral BoNT-A injection into the striatum, a significant 8.5% increase of the D2/D3R availability in the ipsilateral OB and concomitant improvement of olfactory performance were detectable. Based on tract-tracing meta-analysis, we speculate that this may be due to indirect connections between the striatum and the OB.
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Toxinas Botulínicas Tipo A/administração & dosagem , Bulbo Olfatório/efeitos dos fármacos , Transtornos Parkinsonianos/metabolismo , Receptores de Dopamina D2/metabolismo , Anfetamina , Animais , Apomorfina , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Injeções , Masculino , Bulbo Olfatório/metabolismo , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , Ratos WistarRESUMO
Central pathophysiological pathways of basal ganglia dysfunction imply a disturbed interaction of dopaminergic and cholinergic circuits. In Parkinson's disease (PD) imbalanced cholinergic hyperactivity prevails in the striatum. Interruption of acetylcholine (ACh) release in the striatum by locally injected botulinum neurotoxin A (BoNT-A) has been studied in the rat 6-hydroxydopamine (6-OHDA) model of PD (hemi-PD). The hemi-PD was induced by injection of 6-OHDA into the right medial forebrain bundle. Motor dysfunction provoked by apomorphine-induced contralateral rotation was completely reversed for more than 3 months by ipsilateral intrastriatal application of 1-2 ng BoNT-A. Interestingly, BoNT-A injected alone into the right striatum of naïve rats caused a slight transient ipsilateral apomorphine-induced rotation, which lasted only for about one month. Immunohistochemically, large axonal swellings appeared within the striatum injected with BoNT-A, which we tentatively named BoNT-A-induced varicosities. They contained either choline acetyltransferase or tyrosine hydroxylase. These findings suggest a selective inhibition of evoked release of ACh by locally applied BoNT-A. Intrastriatal application of BoNT-A may antagonize localized relative functional disinhibited hypercholinergic activity in neurodegenerative diseases such as PD avoiding side effects of systemic anti-cholinergic treatment.
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Axônios/patologia , Toxinas Botulínicas Tipo A/uso terapêutico , Corpo Estriado/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Oxidopamina/toxicidade , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/patologia , Rotação/efeitos adversos , Animais , Axônios/fisiologia , Corpo Estriado/patologia , Corpo Estriado/fisiopatologia , Modelos Animais de Doenças , Discinesias/tratamento farmacológico , Discinesias/patologia , Discinesias/fisiopatologia , Cones de Crescimento/efeitos dos fármacos , Cones de Crescimento/patologia , Cones de Crescimento/ultraestrutura , Masculino , Regeneração Nervosa/fisiologia , Neurotoxinas/uso terapêutico , Transtornos Parkinsonianos/etiologia , Ratos , Ratos WistarRESUMO
Parkinson's patients often suffer from depression and anxiety, for which there are no optimal treatments. Hemiparkinsonian (hemi-PD) rats were used to test whether intrastriatal Botulinum neurotoxin-A (BoNT-A) application could also have antidepressant-like properties in addition to the known improvement of motor performance. To quantify depression- and anxiety-like behavior, the forced swim test, tail suspension test, open field test, and elevated plus maze test were applied to hemi-PD rats injected with BoNT-A or vehicle. Furthermore, we correlated the results in the forced swim test, open field test, and elevated plus maze test with the rotational behavior induced by apomorphine and amphetamine. Hemi-PD rats did not show significant anxiety-like behavior as compared with Sham 6-OHDA- + Sham BoNT-A-injected as well as with non-injected rats. However, hemi-PD rats demonstrated increased depression-like behaviors compared with Sham- or non-injected rats; this was seen by increased struggling frequency and increased immobility frequency. Hemi-PD rats intrastriatally injected with BoNT-A exhibited reduced depression-like behavior compared with the respective vehicle-receiving hemi-PD animals. The significant effects of intrastriatally applied BoNT-A seen in the forced swim test are reminiscent of those found after various antidepressant drug therapies. Our data correspond with the efficacy of BoNT-A treatment of glabellar frown lines in treating patients with major depression and suggest that also intrastriatal injected BoNT-A may have some antidepressant-like effect on hemi-PD.
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Antidepressivos/uso terapêutico , Toxinas Botulínicas Tipo A/uso terapêutico , Anfetamina , Animais , Apomorfina , Comportamento Animal , Toxinas Botulínicas Tipo A/administração & dosagem , Corpo Estriado , Modelos Animais de Doenças , Injeções , Masculino , Atividade Motora , Oxidopamina , Doença de Parkinson , Transtornos Parkinsonianos , Ratos , Ratos WistarRESUMO
In Parkinson's disease, dopamine depletion leads to hyperactivity of cholinergic interneurons in the caudate-putamen (CPu). Botulinum neurotoxin-A (BoNT-A) inhibits the release of acetylcholine in the peripheral nervous system and is also thought to act as a local anticholinergic drug when injected intrastriatally. In hemiparkinsonian (hemi-PD) rats, a unilateral intrastriatal injection of 1 ng BoNT-A significantly diminished apomorphine-induced rotation behavior for at least 3 months, the effect fading thereafter. A second intrastriatal BoNT-A application, 6 months after the first one, led to a stronger and longer-lasting, beneficial behavioral reaction. As a single BoNT-A injection was not cytotoxic in the rat striatum and resembled BoNT-A treatment in clinical practice, here, we investigated the structural outcome of repeated intrastriatal BoNT-A injections with respect to striatal volume, the number of choline acetyltransferase-immunoreactive (ChAT-ir) interneurons and of the length of their dendritic arbors, and the numeric density of ChAT-ir BoNT-A-induced varicosities (BiVs). Repeated unilateral intrastriatal BoNT-A application decreased the volume of the injected CPu, but did not significantly change the number of striatal ChAT-ir interneurons. Also, the total dendrite length of ChAT-ir interneurons after repeated BoNT-A application resembled the values in double vehicle-injected hemi-PD rats. In repeatedly BoNT-A-injected hemi-PD rats, the numeric density of ChAT-ir BiVs in the CPu was increased compared with rats only intrastriatally injected once with BoNT-A. Even repeated BoNT-A injections in rat striata did not cause substantial morphological changes in ChAT-ir neuron, except for the increased numeric density of ChAT-ir BiVs.
Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Interneurônios/metabolismo , Doença de Parkinson/fisiopatologia , Animais , Comportamento Animal/efeitos dos fármacos , Toxinas Botulínicas/administração & dosagem , Toxinas Botulínicas/farmacologia , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Colina O-Acetiltransferase/metabolismo , Corpo Estriado/efeitos dos fármacos , Modelos Animais de Doenças , Interneurônios/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Neostriado/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/fisiopatologia , Ratos , Ratos WistarRESUMO
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.
Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Donepezila/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Transtornos Parkinsonianos/tratamento farmacológico , Animais , Apomorfina , Comportamento Animal/efeitos dos fármacos , Corpo Estriado , Injeções , Masculino , Atividade Motora/efeitos dos fármacos , Transtornos Parkinsonianos/induzido quimicamente , Ratos WistarRESUMO
Different morphological changes in the caudate-putamen (CPu) of naïve rats and mice were observed after intrastriatal botulinum neurotoxin-A (BoNT-A) injection. For this purpose we here studied various motor behaviors in mice (n = 46) longitudinally up to 9 months after intrastriatal BoNT-A administration as previously reported for rats, and compared both outcomes. Apomorphine- and amphetamine-induced rotational behavior, spontaneous motor behavior, as well as lateralized neglect were studied in mice after the injection of single doses of BoNT-A into the right CPu, comparing them with sham-injected animals. Unilateral intrastriatal injection of BoNT-A in mice induced significantly increased contralateral apomorphine-induced rotations for 1 to 3 months, as well as significantly increased contralateral amphetamine-induced rotations 1 to 9 months after injection. In rats (n = 28), unilateral BoNT-A injection also induced significantly increased contralateral apomorphine-induced rotations 3 months after injection, but did not provoke amphetamine-induced rotations at all. Lateralized sensorimotor integration, forelimb preference, and forelimb stepping were significantly impaired on the left side. The differences in motor behaviors between rats and mice may be caused by different BoNT-A effects on cholinergic and catecholaminergic fibers in rat and mouse striata, interspecies differences in striatal receptor densities, and different connectomes of the basal ganglia.