Slaughter by ventral neck incision (VNI) is performed on some animals without prior stunning in New Zealand and other countries. A single incision with a razor sharp blade is made in the ventral aspect of the neck, sectioning both carotid arteries and jugular veins, though, not the vertebral arteries. There are a number of potential welfare concerns surrounding slaughter by VNI including pain due to the incision, which may lead to distress during the time before loss of consciousness. The aims of this thesis were to identify cortical responses indicative of noxious stimulation due to slaughter by VNI using analysis of the electroencephalogram (EEG) power spectrum and to investigate the effects of non-penetrative captive bolt (NPCB) stunning on these cortical responses. The studies utilised adaptations of a minimal anaesthesia model, which has been validated in a range of mammalian species. Surgical dehorning was used as a validation technique for this methodology in cattle and demonstrated a ‘typical’ EEG response to noxious stimulation. Cattle slaughtered by VNI without prior stunning produced specific responses in the EEG that strongly indicated responses to noxious stimulation. Causation was investigated in cattle where blood flow through the brain remained intact during neck tissue incision (NTI) or the major blood vessels of the neck were isolated and transected independently of other neck tissues (BVT). The response to neck incision in intact animals was principally due to the noxious sensory input due to incision of neck tissues and not mainly as a result of loss of blood flow through the brain. NPCB stunning produced states of cortical activity that were incompatible with the maintenance of sensibility and pain perception. Experimental examination of the time to onset of undoubted insensibility was attempted in cattle subsequent to a pilot study in sheep. The generation of somatosensory-evoked potentials was problematic in cattle. The conclusions of this thesis are that incision of neck tissues during slaughter without prior stunning constitutes a substantial noxious stimulus. Were an animal conscious, this stimulus would be perceived as painful until the onset of hypoxiainduced insensibility. This would represent a significant compromise to animal welfare.

Slaughter by ventral neck incision (VNI) is performed on some animals without prior stunning in New Zealand and other countries. A single incision with a razor sharp blade is made in the ventral aspect of the neck, sectioning both carotid arteries and jugular veins, though, not the vertebral arteries. There are a number of potential welfare concerns surrounding slaughter by VNI including pain due to the incision, which may lead to distress during the time before loss of consciousness. The aims of this thesis were to identify cortical responses indicative of noxious stimulation due to slaughter by VNI using analysis of the electroencephalogram (EEG) power spectrum and to investigate the effects of non-penetrative captive bolt (NPCB) stunning on these cortical responses. The studies utilised adaptations of a minimal anaesthesia model, which has been validated in a range of mammalian species. Surgical dehorning was used as a validation technique for this methodology in cattle and demonstrated a ‘typical’ EEG response to noxious stimulation. Cattle slaughtered by VNI without prior stunning produced specific responses in the EEG that strongly indicated responses to noxious stimulation. Causation was investigated in cattle where blood flow through the brain remained intact during neck tissue incision (NTI) or the major blood vessels of the neck were isolated and transected independently of other neck tissues (BVT). The response to neck incision in intact animals was principally due to the noxious sensory input due to incision of neck tissues and not mainly as a result of loss of blood flow through the brain. NPCB stunning produced states of cortical activity that were incompatible with the maintenance of sensibility and pain perception. Experimental examination of the time to onset of undoubted insensibility was attempted in cattle subsequent to a pilot study in sheep. The generation of somatosensory-evoked potentials was problematic in cattle. The conclusions of this thesis are that incision of neck tissues during slaughter without prior stunning constitutes a substantial noxious stimulus. Were an animal conscious, this stimulus would be perceived as painful until the onset of hypoxiainduced insensibility. This would represent a significant compromise to animal welfare.

No description available.

<p>Volumetric segmentation of brain sub-cortical structures within the basal ganglia and thalamus from Magnetic Resonance Image (MRI) is necessary for non-invasive diagnosis and neurosurgery planning. This is a challenging problem due in part to limited boundary information between structures, similar intensity profiles across the different structures, and low contrast data. With recent advances in ultrahigh-field MR technology, direct identification and clear visualization of such brain sub-cortical structures are facilitated. This dissertation first presents a semi-automatic segmentation system exploiting the visual benefits of ultrahigh-field MRI. The proposed approach utilizes the complementary edge information in the multiple structural MRI modalities. It combines optimally selected two modalities from susceptibility-weighted, T2-weighted, and diffusion MRI, and introduces a tailored new edge indicator function. In addition to this, prior shape and configuration knowledge of the sub-cortical structures are employed in order to guide the evolution of geometric active surfaces. Neighboring structures are segmented iteratively, constraining over-segmentation at their borders with a non-overlapping penalty. Experiments with data acquired on a 7 Tesla (T) MRI scanner demonstrate the feasibility and power of the approach for the segmentation of basal ganglia components critical for neurosurgery applications such as Deep Brain Stimulation (DBS) surgery. </p><p>DBS surgery on brain sub-cortical regions within the Basal ganglia and thalamus is an effective treatment to alleviate symptoms of neuro-degenerative diseases. Particularly, the DBS of subthalamic nucleus (STN) has shown important clinical efficacy for Parkinson’s disease (PD). While accurate localization of the STN and its substructures is critical for precise DBS electrode placement, direct visualization of the STN in current standard clinical MR imaging (e.g., 1.5-3T) is still elusive. Therefore, to locate the target, DBS surgeons today often rely on consensus coordinates, lengthy and risky micro-electrode recording (MER), and patient’s behavioral feedback. Recently, ultrahigh-field MR imaging allows direct visualization of brain sub-cortical structures. However, such high fields are not clinically available in practice. This dissertation also introduces a non-invasive automatic localization method of the STN which is one of the critical targets for DBS surgery in a standard clinical scenario (1.5T MRI). The spatial dependency between the STN and potential predictor structures from 7T MR training data is first learned using the regression models in a bagging way. Then, given automatically detected such predictors on the clinical patient data, the complete region of the STN is predicted as a probability map using learned high quality information from 7T. Furthermore, a robust framework is proposed to properly weight different training subsets, estimating their influence in the prediction accuracy. The STN prediction on the clinical 1.5T MR datasets from 15 PD patients is performed within the proposed approach. Experimental results demonstrate that the developed framework enables accurate prediction of the STN, closely matching the 7T ground truth.</p> / Dissertation

No description available.

Le but de cette thèse était la recherche de biomarqueurs des troubles de l'humeur (dépression unipolaire et troubles bipolaires). Compte tenu de l'étiologie de ces troubles (hypométabolisme du cortex préfrontal dorso-latéral et déficit de la neurotransmission GABA/glutamatergique), nous avons choisi d'étudier deux biomarqueurs : la performance saccadique et l'excitabilité corticale. Nos résultats montrent que les performances saccadiques (antisaccades) permettent (i) de discriminer les patients présentant des troubles de l'humeur de sujets sains, (ii) d'objectiver l'amélioration thymique des patients suite à un traitement, et (iii) d'évaluer l'effet neuromodulateur à court-terme d'une séance de stimulation magnétique transcrânienne répétée. Concernant les mesures d'excitabilité corticale, aucune différence liée à l'amélioration thymique des patients, ni de différences entre patients et contrôles ne ressortent significativement. Nous avons suggéré que le non-contrôle du « State-Dependency » (i.e., de l'« état neurocognitif » des sujets pendant les stimulations) puisse être l'une des causes de l'absence de résultats, et validé cette hypothèse en manipulant les registres cognitifs et émotionnels des sujets.Le second aspect de notre travail de thèse avait trait à l'étude de l'efficacité de la stimulation magnétique transcrânienne répétée (rTMS) comme alternative thérapeutique non médicamenteuse des troubles de l'humeur. Si la littérature s'accorde sur une efficacité significative mais modérée de la rTMS comme traitement, nos données n'ont pas mis en évidence de supériorité du traitement actif par rapport au traitement placebo dans le cas de la neurostimulation iTBS. Une des raisons de ce manque d'efficacité du traitement actif pourrait être liée à des questions d'ordre méthodologique, comme le choix des paramètres de stimulation. Plus généralement, cette absence de résultats incite à questionner le postulat théorique basant l'étude de la réactivité du CPFDL ou sa neuromodulation sur les propriétés du cortex moteur. Notre expérience, étudiant la réactivité de différentes zones corticales par couplage TMS-EEG, va dans ce sens en montrant que la réactivité du cortex moteur diffère de celle des autres cortex. Le couplage TMS-EEG devrait permettre de mieux comprendre l'impact de la neuromodulation rTMS sur la cible corticale visée, et donc d'adapter les paramètres de stimulations aux aires cérébrales stimulées, permettant à terme de traiter plus efficacement les troubles de l'humeur. / The aim of this doctoral thesis was to develop biomarkers for mood disorders (unipolar major depression and bipolar disorders). Considering mood disorders' etiology (Dorso lateral prefrontal cortex hypometabolism and GABA/glutamate neurotransmission deficits), we decided to study two biomarkers: saccadic performance and cortical excitability. Our results showed that saccadic performance (notably Antisaccades) allows (i) discriminating bipolar patients from healthy subjects, (ii) ascertaining patients' mood improvement, and (iii) evaluating the short-term neuromodulation induced by repetitive transcranial magnetic stimulation.Regarding cortical excitability measurements, our results did not reveal any differences neither between patients and healthy subjects, nor between Responders and non Responders to a treatment (Ketamine injection or rTMS). We suggested that the null results could be explained by the lack of control of State-Dependency. This assumption was tested and validated through the manipulation of the subjects' cognitive and emotional states.A second aim of this doctoral thesis was to study the efficacy of rTMS, a non pharmacological therapeutic alternative, as a treatment for mood disorders. Meta-analyses showed that anti depressant effect of rTMS seems to be significant but still moderate. In our experiment, mood improvement did not differ between active and sham rTMS. Basic methodological reasons such as stimulation parameters could explain this lack of efficacy. Overall, one could wonder about the validity of the theoretical postulate of rTMS, drawn upon motor cortex reactivity. This postulate inferred that both cortical reactivity of motor cortex and DLPFC are similar. Using TMS-EEG coupling, we studied the reactivity of these cortices, to TMS pulses, which revealed that motor cortex and DLPFC reactivities should not be assimilated. This result calls into question the relevance of the rTMS theoretical postulate. Coupling TMS and EEG should allow a better understanding of the impact of rTMS neuromodulatory effect over the targeted area, and thus to a better adaption of the stimulation parameters, which could lead to an improvement of rTMS efficacy as a treatment for mood disorders.

Les modèles actuels de perception de la parole suggèrent un couplage étroit entre les rythmes cérébraux, caractérisés par les oscillations neuronales, et le rythme de la parole, permettant de segmenter le flux verbal continu en unités linguistiques pertinentes pour la reconnaissance. En particulier, les modulations lentes d’amplitude de l’enveloppe temporelle de la parole, véhiculant l’information syllabique et prosodique, sont capables d’« entrainer » les oscillations corticales auditives dans la bande de fréquence thêta (4-7 Hz), échantillonnant le signal verbal en unités syllabiques. L’information temporelle qui caractérise la parole joue un rôle fondamental dans l’acquisition et le développement du langage ; un déficit de traitement des indices rythmiques de la parole a d’ailleurs été décrit dans les troubles développementaux du langage. L’objectif de ce travail de thèse était de mieux comprendre les processus neurocognitifs sous-tendant la perception du rythme de la parole naturelle chez l’enfant présentant un développement langagier typique ou atypique (dysphasie) dans trois études. Une première étude en magnétoencéphalographie (MEG) a permis de dévoiler la dynamique corticale oscillatoire chez des enfants francophones neurotypiques (8-13 ans) lors de l’écoute de phrases naturellement produites à un débit normal ou rapide. Nos résultats suggèrent l’existence de deux phénomènes d’« entrainment » des oscillations sur l’enveloppe temporelle de la parole à débit normal, l’un dans la bande thêta au sein des régions auditives droites, l’autre dans une bande centrée sur le débit syllabique moyen des stimuli dans les régions temporales antérieures gauches. Dans la condition de parole rapide, une synchronisation cortico-acoustique a été mise en évidence dans la bande thêta au sein des régions (pré)motrices gauches, reflétant le rôle de la voie dorsale d’intégration sensori-motrice dans les conditions d’écoute difficiles mais aussi dans le développement du langage oral. Les deux études suivantes ont été réalisées chez des enfants présentant une dysphasie expressive (8-13 ans) afin de tester l’hypothèse d’un trouble de traitement du rythme syllabique chez ces enfants, potentiellement sous-tendu par une dynamique corticale oscillatoire atypique. Dans une étude comportementale, nous avons évalué les capacités des enfants dysphasiques à décoder de la parole naturellement produite à débit normal ou rapide, ou accélérée artificiellement. Nous avons montré des performances réduites chez ces enfants, en regard d’enfants neurotypiques, pour traiter des phrases accélérées naturellement et artificiellement, suggérant un déficit d’extraction du rythme de la parole lorsque la fréquence des modulations de l’enveloppe temporelle augmente. Une étude en MEG, identique à celle réalisée chez les enfants neurotypiques, nous a permis d’apporter de premiers éléments en faveur de cette interprétation en révélant un traitement cortical atypique de l’information syllabique dans la dysphasie, qui pourrait rendre compte des troubles phonologiques et morpho-syntaxiques souvent décrits dans ce trouble neuro-développemental. Une synchronisation réduite des oscillations thêta du cortex auditif a ainsi été mise en évidence chez les enfants dysphasiques par rapport à leurs pairs lors de la perception de parole à débit normal. L’absence d’alignement de l’activité oscillatoire des régions prémotrices sur l’enveloppe temporelle des phrases à débit rapide nous a en outre conduit à émettre l’hypothèse d’un dysfonctionnement de la voie dorsale chez ces enfants. Dans l’ensemble, ce travail de thèse fournit donc, pour la première fois à notre connaissance, des preuves expérimentales (i) de la synchronisation entre rythmes corticaux et rythme de la parole naturelle chez les enfants à développement langagier typique et (ii) d’une dynamique oscillatoire atypique lors de la perception de parole à débit normal et rapide chez les enfants dysphasiques. / Current models of speech perception suggest a close correspondence between brain rhythms, characterized by neuronal oscillations, and speech rhythm, which would allow the brain to parse the incoming speech signal into relevant linguistic units for decoding. Slow amplitude modulations in speech temporal envelope, which convey syllabic and prosodic information, have been shown to entrain oscillatory activity of auditory cortex in the theta frequency band (4-7 Hz), sampling the acoustic signal into syllable-sized units. Temporal information in speech is a foundation for oral language acquisition and development; accordingly, deficits in processing speech rhythmic cues have been described in developmental language disorders. This thesis sought to throw light on the neurocognitive processes underlying the perception of natural speech in children with typical and atypical language development (Specific Language Impairment – SLI – or Developmental Language Disorder – DLD) in three experimental studies. In a first magnetoencephalography (MEG) study, we unraveled the oscillatory dynamics in a group of French-speaking typically-developing children aged 8 to 13 years old during listening to naturally-produced sentences either at a normal or fast rate. Our results suggested two types of entrainment of cortical oscillations on the temporal envelope of normal rate speech: the first one occurred in the theta band in right auditory cortex whereas the second one was found in a frequency band centered on the mean syllabic rate of our stimuli in left anterior temporal regions. As to the fast rate condition, we showed cortico-acoustic coupling in the theta band in left (pre)motor areas, reflecting the role of the sensorimotor dorsal pathway in challenging listening conditions as well as in language development. In two other studies, we tested the hypothesis of an impairment to process speech syllabic rhythm, potentially underpinned by atypical oscillatory cortical dynamics, in children with developmental language disorders mainly at the expressive level. In a behavioral study, we examined how French-speaking children with expressive DLD (8-13 years old) processed speech naturally produced at a normal or fast rate, or artificially accelerated. Our results showed poorer performance to decode fast sentences, either accelerated naturally or artificially, in these children as compared to their typically-developing peers, which suggests a deficit in extracting speech syllabic information with increased modulation frequency in the amplitude envelope. The last study, identical to the first one in MEG conducted in typically-developing children, provided the first piece of evidence in favor of this interpretation by showing atypical cortical processing of syllabic information in children with DLD, which may account for the phonological and morpho-syntactic deficits frequently described in this developmental disorder. Reduced alignment of theta oscillatory activity in auditory cortex to normal rate speech has indeed been evidenced in children with DLD as compared to typically-developing children. Lack of synchronization of oscillations in left (pre)motor regions to amplitude envelope of fast rate sentences was also observed, which we interpreted as potential dysfunction of the dorsal stream in this population. To the best of our knowledge, the findings obtained in this thesis therefore provide first experimental evidence for (i) coupling between brain rhythms and rhythm of naturally produced speech in typically-developing children and (ii) atypical oscillatory cortical dynamics underlying normal and fast rate speech in children with developmental language disorders.

Chez le rongeur, lorsque l’expression d’une peur conditionnée au contexte s’appuie sur un souvenir ancien, des réponses de peur importantes sont souvent rapportées lors de l’exposition à un contexte différent de celui dans lequel les chocs électriques ont été administrés. Cette généralisation des réponses de peur serait liée à une réorganisation concomitante des réseaux sous-tendant l’expression de la peur, en particulier à un « désengagement » de l’hippocampe dans le rappel des informations contextuelles. Cependant, d’autres études suggèrent que des modifications dans les traitements amenant à l’expression de comportements défensifs, liés à la peur ou l’anxiété, puissent également se mettre en place avec le temps suite à un conditionnement. Ainsi, une incubation des réponses de peur, correspondant à une augmentation globale des niveaux de peur avec le temps, pourrait contribuer à la généralisation de ces réponses. Nos travaux, par une approche d’imagerie de gènes précoces immédiats ainsi que d’évaluation comportementale, ont visé à démêler les mécanismes impliqués dans la généralisation de la peur conditionnée au contexte accompagnant sa consolidation à long terme. Nos résultats suggèrent que la généralisation soit moins liée à une altération du souvenir du contexte qu’à des modifications portant sur le traitement et / ou l’expression des émotions. La nature de ces dernières modifications semble dépendre du statut prédictif initial du contexte (en avant- ou en arrière-plan). De manière cohérente avec l’observation d’une absence de dégradation de la trace du contexte avec le temps, le rôle de l’hippocampe dans le rappel de l’information contextuelle nous est apparu maintenu au cours du temps. Les réorganisations observées dans les réseaux sous-tendant l’expression des réponses de peur concerneraient plutôt des modifications liées au traitement associatif et / ou émotionnel des informations contextuelles. Dans leur ensemble, nos résultats soulèvent la nécessaire prise en compte du haut degré de complexité des traitements amenant à l’expression d’une peur conditionnée, pour qui souhaite évaluer la qualité de la représentation contextuelle sur la base de réponses de peur discriminantes. / At remote delays following contextual fear conditioning in rodents, generalization of fear responses is usually described, as fear responses are elicited by exposure to a context different from the one in which footshocks were delivered. This generalization has been proposed to rely on the degradation and/or transformation of the memory trace due to systemic consolidation. The latter corresponds to the time-dependent reorganization of structures implicated in contextual fear expression, from networks involving the hippocampus to mainly cortical networks. However, other studies suggest that changes in defensive behaviors’ expression tied to fear and anxiety might take place in the time period following a fear conditioning experience. Indeed, an incubation of fear responses, that is an overall increase in fear responses following contextual fear conditioning, has repeatedly been reported. Such changes in the processing of emotionally relevant information might represent an alternative explanation of a time-dependent generalization of fear responses. Using immediate early genes imaging and behavioral assessment, our studies aimed at disentangling the processes supporting fear generalization over time. Our results suggest that under some circumstances, changes in the fear responses’ specificity might less be due to the dynamics of a memory system supporting the context representation than to alterations attributable to emotional information processing and/or expression. They point out dissociations in the latter changes between animals conditioned to a foreground or a background context. Consistent with our observation of a preserved detailed context memory trace, they also suggest that changes in the brain networks supporting the expression of a remotely acquired contextual fear might not reflect a time-dependent hippocampal-independency. Rather, the observed reorganization of neuronal networks might sustain changes in the associative and / or emotional information processing evoked by context exposure. Altogether, our results point out the need to take account of the high complexity of information processing leading to the onset of fear responses, when trying to infer the quality of a contextual representation on the basis of fear discrimination between contexts.

Contexte : Les hémorragies intracérébrales spontanées (HIC) sont grevées d’une mortalité élevée et d’un pronostic fonctionnel sombre. Les données concernant le pronostic à long terme des HIC sont rares. L’objectif principal de ce travail était d’étudier le pronostic au long cours des HIC en les abordant par le prisme de leur histoire naturelle.Méthodes : Nos populations d’étude sont issues de la cohorte prospective PITCH (Prognosis of IntraCerebral Haemorrhage) qui est une cohorte observationnelle ayant inclus de façon consécutive tous les patients admis au CHU de Lille pour une HIC spontanée entre 2004 et 2009. Nous avons étudié (i) l’incidence de la démence de novo post HIC ainsi que les facteurs prédictifs cliniques et neuroradiologiques associés à sa survenue ; (ii) la prévalence de la sidérose superficielle corticale (SSc) et les facteurs cliniques et radiologiques associés ; (iii) les facteurs prédictifs de récidive hémorragiques.Résultats : Nous avons mis en évidence qu’il existait un risque majeur de démence de novo chez les patients survivant à une HIC. Les facteurs prédictifs de démence identifiés tels que la localisation lobaire ou la SSc suggèrent une implication directe de l’angiopathie amyloïde cérébrale. Nous avons également montré qu’au sein de notre cohorte, un patient sur cinq avait de la SSc sur l’IRM cérébrale réalisée à l’admission. La SSc apparaissait être un facteur neuroradiologique prédictif majeur de récidive hémorragique.Conclusion : Les résultats de ce travail ont un impact important dans la prise en charge des patients ayant eu une HIC spontanée et permettront d’informer de façon adéquate les patients et leurs aidants. Ils apportent des informations nouvelles sur l’évaluation du risque de récidive hémorragique et sur d’éventuelles futures cibles thérapeutiques. / Background: The low frequency of spontaneous intracerebral haemorrhage (ICH) and its high mortality rate may explain the paucity of data in long term outcomes. The main objective was to study long term prognosis of ICH through the prism of their natural history.Methods: Our study populations were based on the PITCH (Prognosis of IntraCerebral Haemorrhage) cohort which is an observational study that included consecutively adults admitted at the Lille University Hospital for spontaneous ICH between 2004 and 2009. We aimed to determine (i) the incidence of new onset dementia and its clinical and radiological predictive factors; (ii) the prevalence of cortical superficial siderosis (cSS) and its associated factors; (iii) predictive factors of recurrent ICH.Results: We showed that the risk of new onset dementia is substantial after spontaneous ICH. Predictive factors of new onset dementia such as ICH lobar location and cSS suggest the implication of underlying cerebral amyloid angiopathy. We found that one out of five patients had cSS on baseline MRI. cSS was a strong predictive factor of recurrent ICH. Conclusion: These findings are of immediate clinical relevance in the management of ICH patients and will allow to adequately inform patients and caregivers. These results may provide additional information on ICH recurrence risk assessment and may contribute to the development of future therapeutic strategies.

Esquizofrenia (SZ) é uma doença multifacetada que afeta vários domínios, incluindo sintomas positivos e negativos. Devido a isso, até o momento, não existe um modelo animal adequado de SZ, o que contribui para o fato de sua fisiopatologia ainda ser pouco conhecida. Um dos melhores modelos animais de SZ desenvolvidos usa acetato metilazoximetanol (MAM), no 17º dia embrionário (MAM-E17) de ratas prenhes, o que leva a alguns dos padrões de histopatologia observados em SZ. O objetivo deste estudo é avaliar o uso do MAM-E17 para validar achados histológicos deste modelo animal de SZ. Um total de 4 controles e 13 MAM-E17 foram estudados. Os ratos submetidos ao tratamento MAM-E17 apresentaram uma diminuição no peso do cérebro e na área do hipocampo caudal esquerdo. Não houve diferença na área do hipocampo caudal direito nem no hipocampo dorsal. Os animais submetidos ao MAM-E17 mostraram uma diminuição na espessura do córtex pré-frontal direito. O modelo de roedor MAM-E17 demonstrou reproduzir os principais aspectos dos achados histológicos altamente relevantes na SZ. Assim, a administração do MAM-E17 pode ser um modelo animal apropriado para o estudo de aspectos histológicos de SZ. Isto é de suma importância para o melhor entendimento e tratamento desta devastadora doença no futuro. / Schizophrenia (SZ) is a multifaceted illness that affects multiple domains, including negative and positive symptons. Because of this, there is no appropriate animal model of SZ, which contributes to its still is poorly understood pathophysiology. One of the bestdeveloped animal models of SZ uses methylazoxymethanol acetate (MAM) in pregnant rat dams on embryonic day 17 (MAM-E17) to procedure patterns of histopathology similar to those observed in SZ. The aim of this study was to evaluate the use of MAM-E17 to validate the histological findings of this animal model of SZ. A total of 4 controls and 13 MAM-E17 were studied. Rats subjected to MAM-E17 treatment presented a decreased in brain weight and in the left caudal hippocampus area. There were no differences in the right caudal hippocampal area or in left and right dorsal hippocampal areas. The animals subjected to MAM-E17 showed a decrease in right prefrontal cortex thickness. The MAME17 rodent model reproduced key aspects of histological findings that are highly relevant in SZ. Thus, the admistration of MAM-E17 may be an appropriate animal model for the study of histological aspects of SZ. This is of paramount importance to the better understanding and treatment of this devastating disease in the future.