Intra-hippocampal administration of the VEGF receptor blocker PTK787/ZK222584 impairs long-term memory.

A number of studies have established a role for vascular endothelial growth factor (VEGF) in angiogenesis. Recent reports have shown that VEGF overexpression in the hippocampus improves learning and memory and is associated with enhanced neurogenesis. PTK787/ZK222584 (PTK/ZK) is a reported inhibitor of VEGFR signaling that is currently being tested for its effects on lung and colon cancer. However, the influence of this drug on cognition has not been examined. In the present study, we questioned if post-training administration of PTK/ZK influences hippocampus-dependent memory. When administered to rats immediately following massed training in the Morris water maze, PTK/ZK impaired spatial memory retention tested 48 h later. This impairment was evidenced by increased latency to the hidden platform and fewer platform crossings. However, this impairment was not associated with a change in neurogenesis during this time frame. PTK/ZK infusion did not reduce VEGFR or AKT phosphorylation, but increased the phosphorylation of ERK. These studies suggest that VEGFR inhibitors such as PTK/ZK may negatively influence cognition.

Subacute neural stem cell therapy for traumatic brain injury.

INTRODUCTION: Traumatic brain injury (TBI) frequently results in devastating and prolonged morbidity. Cellular therapy is a burgeoning field of experimental treatment that has shown promise in the management of many diseases, including TBI. Previous work suggests that certain stem and progenitor cell populations migrate to sites of inflammation and improve functional outcome in rodents after neural injury. Unfortunately, recent study has revealed potential limitations of acute and intravenous stem cell therapy. We studied subacute, direct intracerebral neural stem and progenitor cell (NSC) therapy for TBI. MATERIALS AND METHODS: The NSCs were characterized by flow cytometry and placed (400,000 cells in 50 muL 1x phosphate-buffered saline) into and around the direct injury area, using stereotactic guidance, of female Sprague Dawley rats 1 wk after undergoing a controlled cortical impact injury. Immunohistochemistry was used to identify cells located in the brain at 48 h and 2 wk after administration. Motor function was assessed using the neurological severity score, foot fault, rotarod, and beam balance. Cognitive function was assessed using the Morris water maze learning paradigm. Repeated measures analysis of variance with post-hoc analysis were used to determine significance at P < 0.05. RESULTS: Immunohistochemistry analysis revealed that 1.4-1.9% of infused cells remained in the neural tissue at 48 h and 2 wk post placement. Nearly all cells were located along injection tracks at 48 h. At 2 wk some cell dispersion was apparent. Rotarod motor testing revealed significant increases in maximal speed among NSC-treated rats compared with saline controls at d 4 (36.4 versus 27.1 rpm, P < 0.05) and 5 (35.8 versus 28.9 rpm, P < 0.05). All other motor and cognitive evaluations were not significantly different compared to controls. CONCLUSIONS: Placement of NSCs led to the cells incorporating and remaining in the tissues 2 wk after placement. Motor function tests revealed improvements in the ability to run on a rotating rod; however, other motor and cognitive functions were not significantly improved by NSC therapy. Further examination of a dose response and optimization of placement strategy may improve long-term cell survival and maximize functional recovery.

Sulforaphane improves cognitive function administered following traumatic brain injury.

Recent studies have shown that sulforaphane, a naturally occurring compound that is found in cruciferous vegetables, offers cellular protection in several models of brain injury. When administered following traumatic brain injury (TBI), sulforaphane has been demonstrated to attenuate blood-brain barrier permeability and reduce cerebral edema. These beneficial effects of sulforaphane have been shown to involve induction of a group of cytoprotective, Nrf2-driven genes, whose protein products include free radical scavenging and detoxifying enzymes. However, the influence of sulforaphane on post-injury cognitive deficits has not been examined. In this study, we examined if sulforaphane, when administered following cortical impact injury, can improve the performance of rats tested in hippocampal- and prefrontal cortex-dependent tasks. Our results indicate that sulforaphane treatment improves performance in the Morris water maze task (as indicated by decreased latencies during learning and platform localization during a probe trial) and reduces working memory dysfunction (tested using the delayed match-to-place task). These behavioral improvements were only observed when the treatment was initiated 1h, but not 6h, post-injury. These studies support the use of sulforaphane in the treatment of TBI, and extend the previously observed protective effects to include enhanced cognition.

Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in infant rats.

In an infant rat model of pneumococcal meningitis the effect of dexamethasone on neuronal injury in the hippocampus and on learning disability after recovery from the disease was examined. Treatment with dexamethasone or vehicle was started 18 h after infection, concomitant with antibiotics. Neuronal apoptosis in the hippocampal dentate gyrus 34 h after infection was significantly aggravated by dexamethasone treatment compared with vehicle controls (p = 0.02). Three weeks after acute pneumococcal meningitis, learning capacity of animals was assessed in the Morris water maze. The results showed a significantly impaired learning performance of infected animals treated with dexamethasone compared with vehicle controls (p = 0.01). Dexamethasone had no effect on hippocampal injury or learning in uninfected controls. Thus, dexamethasone as adjuvant therapy increased hippocampal cell injury and reduced learning capacity in this model of pneumococcal meningitis in infant rats.

The mood-stabilizer lithium prevents hippocampal apoptosis and improves spatial memory in experimental meningitis.

Pneumococcal meningitis is associated with high morbidity and mortality rates. Brain damage caused by this disease is characterized by apoptosis in the hippocampal dentate gyrus, a morphological correlate of learning deficits in experimental paradigms. The mood stabilizer lithium has previously been found to attenuate brain damage in ischemic and inflammatory diseases of the brain. An infant rat model of pneumococcal meningitis was used to investigate the neuroprotective and neuroregenerative potential of lithium. To assess an effect on the acute disease, LiCl was administered starting five days prior to intracisternal infection with live Streptococcus pneumoniae. Clinical parameters were recorded, cerebrospinal fluid (CSF) was sampled, and the animals were sacrificed 42 hours after infection to harvest the brain and serum. Cryosections of the brains were stained for Nissl substance to quantify brain injury. Hippocampal gene expression of Bcl-2, Bax, p53, and BDNF was analyzed. Lithium concentrations were measured in serum and CSF. The effect of chronic lithium treatment on spatial memory function and cell survival in the dentate gyrus was evaluated in a Morris water maze and by quantification of BrdU incorporation after LiCl treatment during 3 weeks following infection. In the hippocampus, LiCl significantly reduced apoptosis and gene expression of Bax and p53 while it increased expression of Bcl-2. IL-10, MCP-1, and TNF were significantly increased in animals treated with LiCl compared to NaCl. Chronic LiCl treatment improved spatial memory in infected animals. The mood stabilizer lithium may thus be a therapeutic alternative to attenuate neurofunctional deficits as a result of pneumococcal meningitis.

"Leiomyomatoid angiomatous neuroendocrine tumor" (LANT) of the pituitary reflects idiosyncratic angiogenesis in adenomas of the gonadotroph cell lineage.

Based on a single-case observation, the descriptive label "leiomyomatoid angiomatous neuroendocrine tumor" (LANT) has been tentatively applied to what was perceived as a possible novel type of dual-lineage pituitary neoplasm with biphasic architecture. We report on two additional examples of an analogous phenomenon encountered in male patients, aged 59 years (Case 1) and 91 years (Case 2). Both tumors were intra- and suprasellar masses, measuring 5.6 cm × 4.4 cm × 3.4 cm, and 2.7 cm × 2 cm × 1.7 cm, respectively. Histologically, Case 1 was an FSH-cell adenoma interwoven by vascularized connective tissue septa that tended to exhibit incremental stages of adventitial overgrowth. The epithelial component of Case 2 corresponded to an LH-cell adenoma, and lay partitioned by a maze of paucicellular to hyalinized vascular axes. Irrespective of architectural variations, perivascular spindle cells exhibited immunopositivity for vimentin, muscular actin, and smooth muscle actin. Conversely, negative results were obtained for CD34, EMA, S100 protein, GFAP, and TTF-1. Ultrastructural study failed to reveal metaplastic cell forms involving transitional features between adenohypophyseal-epithelial and mesenchymal-contractile phenotype. We propose that LANT be regarded as a peculiar reflection of maladaptive angiogenesis in some pituitary adenomas, rather than a genuine hybrid neoplasm. While no mechanistic clue is forthcoming to account for this distinctive pattern, hemodynamic strain through direct arterial - rather than portal - supply of the adenoma's capillary bed may be one such explanatory factor. The apparent predilection of the LANT pattern for macroadenomas of the gonadotroph cell lineage remains unexplained.

An Exploration Based Cognitive Bias Test for Mice: Effects of Handling Method and Stereotypic Behaviour

Behavioural tests to assess affective states are widely used in human research and have recently been extended to animals. These tests assume that affective state influences cognitive processing, and that animals in a negative affective state interpret ambiguous information as expecting a negative outcome (displaying a negative cognitive bias). Most of these tests however, require long discrimination training. The aim of the study was to validate an exploration based cognitive bias test, using two different handling methods, as previous studies have shown that standard tail handling of mice increases physiological and behavioural measures of anxiety compared to cupped handling. Therefore, we hypothesised that tail handled mice would display a negative cognitive bias. We handled 28 female CD-1 mice for 16 weeks using either tail handling or cupped handling. The mice were then trained in an eight arm radial maze, where two adjacent arms predicted a positive outcome (darkness and food), while the two opposite arms predicted a negative outcome (no food, white noise and light). After six days of training, the mice were also given access to the four previously unavailable intermediate ambiguous arms of the radial maze and tested for cognitive bias. We were unable to validate this test, as mice from both handling groups displayed a similar pattern of exploration. Furthermore, we examined whether maze exploration is affected by the expression of stereotypic behaviour in the home cage. Mice with higher levels of stereotypic behaviour spent more time in positive arms and avoided ambiguous arms, displaying a negative cognitive bias. While this test needs further validation, our results indicate that it may allow the assessment of affective state in mice with minimal training— a major confound in current cognitive bias paradigms.

Behavioral Implications of Knockout for the Dyslexia-Risk Gene Dcdc2 in Mice

Several genetic linkage and epidemiological studies have provided strong evidence that DCDC2 is a candidate gene for developmental dyslexia, a disorder that impairs a person’s reading ability despite adequate intelligence, education, and socio-economic status. Studies investigating embryonic intra-ventricular RNA interference (RNAi) of Dcdc2, a rat homolog of the DCDC2 gene in humans, indicate disruptions in neuronal migration in the rat cortex during development. Interestingly, these anatomical anomalies are consistent with post mortem histological analysis of human dyslexic patients. Other rodent models of cortical developmental disruption have shown impairment in rapid auditory processing and learning maze tasks in affected subjects. The current study investigates the rapid auditory processing abilities of mice heterozygous for Dcdc2 (one functioning Dcdc2 allele) and mice with a homozygous knockout of Dcdc2 (no functioning Dcdc2 allele). It is important to note that this genetic model for behavioral assessment is still in the pilot stage. However, preliminary results suggest that mice with a genetic mutation of Dcdc2 have impaired rapid auditory processing, as well as non-spatial maze learning and memory ability, as compared to wildtypes. By genetically knocking out Dcdc2 in mice, behavioral features associated with Dcdc2 can be characterized, along with other neurological abnormalities that may arise due to the loss of the functioning gene.

Diagnosing the Prodromal State of Alzheimer's Disease

Mild Cognitive Impairment- Amnestic Subtype (MCIa) is a putative prodromal stage of Alzheimer’s Disease (AD) characterized by focal deficits in episodic verbal memory. Less is known about relative deficits in visuospatial learning, although there is ample evidence indicating involvement of the hippocampus in visuospatial learning, as well as hippocampal degeneration in early AD. The aim of this study was to better characterize the components of working memory dysfunction in people with MCIa to increase the ability to reliably diagnose this disease. Fifty-six elderly adults diagnosed with MCIa and 94 healthy elderly completed a hidden maze learning task. Results indicated similar functioning between groups on measures of reasoning, problem solving, and accuracy. However, MCIa subjects were less efficient at learning the hidden path, making more errors per second on average (Cohen’s d= -.78) and requiring a longer time to complete the maze (Cohen’s d=.77). The learning curve between the first two trials was four times as steep for healthy elderly compared to MCIa (slopes = 4.9 vs. 1.24, respectively), indicating that MCIa subjects exhibited relative difficulty in holding and making effective use of an internal spatial map in order to improve performance. Our results suggest that MCIa patients have focal deficits in visuospatial working memory, with relative preservation of functioning on other more global measures of cognitive functioning. This particular pattern of results may be specific to the amnestic variant of MCI.

Role of entorhinal cortical plasticity in spatial and contextual memory

It is well accepted that the hippocampus (HIP) is important for spatial and contextual memories, however, it is not clear if the entorhinal cortex (EC), the main input/output structure for the hippocampus, is also necessary for memory storage. Damage to the EC in humans results in memory deficits. However, animal studies report conflicting results on whether the EC is necessary for spatial and contextual memory. Memory consolidation requires gene expression and protein synthesis, mediated by signaling cascades and transcription factors. Extracellular-signal regulated kinase (ERK) cascade activity is necessary for long-term memory in several tasks, including those that test spatial and contextual memory. In this work, we explore the role of ERK-mediated plasticity in the EC on spatial and contextual memory. ^ To evaluate this role, post-training infusions of reversible pharmacological inhibitors specific for the ERK cascade that do not affect normal neuronal activity were targeted directly to the EC of awake, behaving animals. This technique provides spatial and temporal control over the inhibition of the ERK cascade without affecting performance during training or testing. Using the Morris water maze to study spatial memory, we found that ERK inhibition in the EC resulted in long-term memory deficits consistent with a loss of spatial strategy information. When animals were allowed to learn and consolidate a spatial strategy for solving the task prior to training and ERK inhibition, the deficit was alleviated. To study contextual memory, we trained animals in a cued fear-conditioning task and saw an increase in the activation of ERK in the EC 90 minutes following training. ERK inhibition in the EC over this time point, but not at an earlier time point, resulted in increased freezing to the context, but not to the tone, during a 48-hour retention test. In addition, animals froze maximally at the time the shock was given during training; similar to naïve animals receiving additional training, suggesting that ERK-mediated plasticity in the EC normally suppresses the temporal nature of the freezing response. These findings demonstrate that plasticity in the EC is necessary for both spatial and contextual memory, specifically in the retention of behavioral strategies. ^

Voces en un campo de sangre : Max Aub y los penúltimos episodios nacionales

Una cierta lectura de la posmodernidad ha diagnosticado (en realidad, ofertado) el final de la historia y, por consiguiente, el de la novela histórica, aunque algunos optamos por no enterrarla sino por renovarla. En el contexto de este debate vale la pena detenerse en el Laberinto mágico de Max Aub, magno mural de la guerra civil española, una de las últimas manifestaciones del modelo puro de episodio nacional, máximo legado de Galdós y Valle Inclán. A pesar de los elementos aparentemente heterogéneos que contiene, el gesto histórico e ideológico que traza Campo cerrado (escrita en 1939), la primera novela del Laberinto mágico, es el de la novela histórica moderna. En los Campos posteriores, la fórmula de la novela histórica aubiana alcanzará su sazón, siendo quizá Campo del moro (1963) el más brillante y equilibrado ejemplo de esta modalidad entre las de la serie. En ella, el sentido de la historia que se anunciaba en Campo del moro se disipa, víctima de la traición y asaltado por la locura que se desata en las calles de Madrid. Campo del moro puede considerarse novela histórica pura, ya que se cumplen en ella las condiciones de felicidad necesarias para que esta modalidad genérica se realice plenamente: historicidad de los acontecimientos; respeto al orden cronológico en que se suceden; ficcionalidad limitada por el referente histórico; iniciativa de lo histórico sobre lo ficcional y primacía de la lógica de lo público sobre la de lo privado; por último, narratibilidad de los acontecimientos que se manifiesta en la selección del golpe de estado de Casado y Besteiro y su potenciación como clave del relato histórico. Tres grandes temas se despliegan en la lógica argumental de la novela: la traición, la confusión del laberinto y la degradación de una causa heroica. En el discurso de Max Aub que alimenta la novela, la ficción, la verdad y la historia se entrelazan hasta formar el hilo de Ariadna en el Laberinto.

Voces en un campo de sangre : Max Aub y los penúltimos episodios nacionales

Una cierta lectura de la posmodernidad ha diagnosticado (en realidad, ofertado) el final de la historia y, por consiguiente, el de la novela histórica, aunque algunos optamos por no enterrarla sino por renovarla. En el contexto de este debate vale la pena detenerse en el Laberinto mágico de Max Aub, magno mural de la guerra civil española, una de las últimas manifestaciones del modelo puro de episodio nacional, máximo legado de Galdós y Valle Inclán. A pesar de los elementos aparentemente heterogéneos que contiene, el gesto histórico e ideológico que traza Campo cerrado (escrita en 1939), la primera novela del Laberinto mágico, es el de la novela histórica moderna. En los Campos posteriores, la fórmula de la novela histórica aubiana alcanzará su sazón, siendo quizá Campo del moro (1963) el más brillante y equilibrado ejemplo de esta modalidad entre las de la serie. En ella, el sentido de la historia que se anunciaba en Campo del moro se disipa, víctima de la traición y asaltado por la locura que se desata en las calles de Madrid. Campo del moro puede considerarse novela histórica pura, ya que se cumplen en ella las condiciones de felicidad necesarias para que esta modalidad genérica se realice plenamente: historicidad de los acontecimientos; respeto al orden cronológico en que se suceden; ficcionalidad limitada por el referente histórico; iniciativa de lo histórico sobre lo ficcional y primacía de la lógica de lo público sobre la de lo privado; por último, narratibilidad de los acontecimientos que se manifiesta en la selección del golpe de estado de Casado y Besteiro y su potenciación como clave del relato histórico. Tres grandes temas se despliegan en la lógica argumental de la novela: la traición, la confusión del laberinto y la degradación de una causa heroica. En el discurso de Max Aub que alimenta la novela, la ficción, la verdad y la historia se entrelazan hasta formar el hilo de Ariadna en el Laberinto.

Classification of coral reef types in Torres Strait (GIS files in zip-archive 319 kB)

Coral reefs represent major accumulations of calcium carbonate (CaCO3). The particularly labyrinthine network of reefs in Torres Strait, north of the Great Barrier Reef (GBR), has been examined in order to estimate their gross CaCO3 productivity. The approach involved a two-step procedure, first characterising and classifying the morphology of reefs based on a classification scheme widely employed on the GBR and then estimating gross CaCO3 productivity rates across the region using a regional census-based approach. This was undertaken by independently verifying published rates of coral reef community gross production for use in Torres Strait, based on site-specific ecological and morphological data. A total of 606 reef platforms were mapped and classified using classification trees. Despite the complexity of the maze of reefs in Torres Strait, there are broad morphological similarities with reefs in the GBR. The spatial distribution and dimensions of reef types across both regions are underpinned by similar geological processes, sea-level history in the Holocene and exposure to the same wind/wave energetic regime, resulting in comparable geomorphic zonation. However, the presence of strong tidal currents flowing through Torres Strait and the relatively shallow and narrow dimensions of the shelf exert a control on local morphology and spatial distribution of the reef platforms. A total amount of 8.7 million tonnes of CaCO3 per year, at an average rate of 3.7 kg CaCO3 m-2 yr-1 (G), were estimated for the studied area. Extrapolated production rates based on detailed and regional census-based approaches for geomorphic zones across Torres Strait were comparable to those reported elsewhere, particularly values for the GBR based on alkalinity-reduction methods. However, differences in mapping methodologies and the impact of reduced calcification due to global trends in coral reef ecological decline and changing oceanic physical conditions warrant further research. The novel method proposed in this study to characterise the geomorphology of reef types based on classification trees provides an objective and repeatable data-driven approach that combined with regional census-based approaches has the potential to be adapted and transferred to different coral reef regions, depicting a more accurate picture of interactions between reef ecology and geomorphology.

Voces en un campo de sangre : Max Aub y los penúltimos episodios nacionales

Una cierta lectura de la posmodernidad ha diagnosticado (en realidad, ofertado) el final de la historia y, por consiguiente, el de la novela histórica, aunque algunos optamos por no enterrarla sino por renovarla. En el contexto de este debate vale la pena detenerse en el Laberinto mágico de Max Aub, magno mural de la guerra civil española, una de las últimas manifestaciones del modelo puro de episodio nacional, máximo legado de Galdós y Valle Inclán. A pesar de los elementos aparentemente heterogéneos que contiene, el gesto histórico e ideológico que traza Campo cerrado (escrita en 1939), la primera novela del Laberinto mágico, es el de la novela histórica moderna. En los Campos posteriores, la fórmula de la novela histórica aubiana alcanzará su sazón, siendo quizá Campo del moro (1963) el más brillante y equilibrado ejemplo de esta modalidad entre las de la serie. En ella, el sentido de la historia que se anunciaba en Campo del moro se disipa, víctima de la traición y asaltado por la locura que se desata en las calles de Madrid. Campo del moro puede considerarse novela histórica pura, ya que se cumplen en ella las condiciones de felicidad necesarias para que esta modalidad genérica se realice plenamente: historicidad de los acontecimientos; respeto al orden cronológico en que se suceden; ficcionalidad limitada por el referente histórico; iniciativa de lo histórico sobre lo ficcional y primacía de la lógica de lo público sobre la de lo privado; por último, narratibilidad de los acontecimientos que se manifiesta en la selección del golpe de estado de Casado y Besteiro y su potenciación como clave del relato histórico. Tres grandes temas se despliegan en la lógica argumental de la novela: la traición, la confusión del laberinto y la degradación de una causa heroica. En el discurso de Max Aub que alimenta la novela, la ficción, la verdad y la historia se entrelazan hasta formar el hilo de Ariadna en el Laberinto.

El parque: Espacios, límites y jerarquías en la obra de SANAA

En los últimos tiempos, el estudio japonés SANAA ha realizado una serie de obras que le han puesto en el punto de mira de la arquitectura internacional, y que se ha visto reflejado en la concesión en el año 2010 del premio Pritzker a Kazuyo Sejima y Ryue Nishizawa por toda una carrera de trabajo ininterrumpido. SANAA ha construido una serie de edificios que han supuesto una gran influencia en el contexto de la arquitectura mundial y que está contribuyendo al trabajo de muchísimos arquitectos jóvenes, tanto en Japón como fuera de él, y su trabajo se estudia y analiza en las escuelas de arquitectura de medio mundo. La tesis doctoral, estudia el parque de SANAA desde las diversas formas en las que éste se presenta, parques por continuidad, o parques por acumulación, como una excusa para el estudio de los diferentes mecanismos arquitectónicos en los que se basa su modo de proyectar. Dichos mecanismos forman parte ya de una forma de proyectar contemporánea y su estudio permite la comprensión de algunos de los fenómenos arquitectónicos más interesantes que se están produciendo en la arquitectura de nuestro tiempo. La revelación de estos mecanismos supone el sacar a la luz gran parte de los procesos y desarrollos de proyecto, que por la lacónica manera de dibujar de SANAA, quedan ocultos la mayoría de las veces y, tan solo es percibido en una visita lenta y pausada por el edificio. El documento aquí presentado se convierte entonces, en una investigación, en la que el doctorando, como un detective, rastrea los proyectos de SANAA buscando aquellos mecanismos que permiten discernir el verdadero significado de conceptos como laberinto, jerarquía, orden, atmósfera o experiencia a lo largo de los principales proyectos de espacio horizontal de Sejima y Nishizawa. La tesis intenta por tanto dar forma a las principales referencias que constituyen el universo imaginario del estudio japonés y que, ya son parte de la cultura arquitectónica contemporánea. ABSTRACT In recent times, the Japanese Studio SANAA has produced a number of works that have taken it to the front sight of international architecture. This has led Kazuyo Sejima and Ryue Nishizawa to receiving the 2010 Pritzer award for an uninterrupted career. SANAA has built a series of buildings that have greatly influenced global architecture. Moreover, it is contributing to the work of many young architects, both in Japan and outside Japan. Its work is studied and assessed by architecture schools all over the world. This Doctoral thesis analyses the SANAA Park from all the perspectives it shows, parks by continuity or parks by accumulation, as an excuse to study different architectural mechanisms in which its way of projecting is based. Such mechanisms already are part of a contemporaneous way of projecting. In addition, its analysis allows for the further understanding of some of the most interesting architectural phenomena that are being produced nowadays. The release of these mechanisms entails shedding a light to most of the proceedings and courses of the project that, because of the SANAA’s laconic way of designing, remain hidden most of the times and are often noticed through a slow and thorough look at the building. This document becomes then a work of research, where the Doctorate, as a detective, tracks SANAA’s projects, searching for those mechanisms that allow for truly defining the meaning of concepts such as maze, hierarchy, order, atmosphere and experience throughout Sejima’s and Nishizawa’s main horizontal space projects. Therefore, this thesis aims at shaping key references that constitute the imaginary universe of the Japanese study and that already are part of the contemporaneous architectural culture.