The first description of the human ventricular system was made in the third century BC by the Greek anatomists Erasistratus (ca. 304 BC–ca. 250 BC) and Herophilus (ca. 335 BC–ca. 280 BC), considered the first anatomists in history (Fig. 1.1). They were founders of the famous School of Medicine of Alexandria and both were allowed to perform dissections and vivisection on humans [1]. Erasistratus considered atoms as the essential elements of the human body, and considered that the atoms were vitalized by external air (pneuma), which circulated through the nerves. He described the heart valves and the sigmoid colon, and also suspected that the heart was not the center of the emotions, but that it worked like a pump. He was one of the first to distinguish veins from arteries, and he also believed that the arteries contained air and carried the vital spirit (pneumazooticon) from the heart. This idea went against the prevailing belief at the time, that of body humors, suggested by Hippocrates. Additionally, Erasistratus is considered to be the first heart arrhythmologist, studying the rhythm of the heart. It is said that he was appointed royal physician after curing Antiochus I Soter, a Seleucid king, son of Seleucus I Nicator. By measuring the heart palpitations of Antiochus, Erasistratus observed the reactions of the ailing man. He noted that when Antiochus’ young and beautiful stepmother, Stratonice, visited him, he had palpitations. Erasistratus concluded that it was the love of Antiochus for her that afflicted him, and so they were allowed to marry [2] (Fig. 1.2).

Herophilus studied the brain in detail, recognizing this organ as the center of the nervous system and intelligence. He described seven pairs of cranial nerves. He also distinguished blood vessels and nerves, including distinguishing the motor nerves from the sensory nerves. Other objects of his study were the eyes, liver, pancreas, salivary glands, digestive system, and genitals. He was one of Hippocrates’ scholars and wrote a treatise on the Hippocratic method. Erasistratus and Herophilus both had a particular interest in brain anatomy and, from the first human dissections known in history, described in the brain four “small stomachs” or “cells”, and their communications with each other. At that time, it was believed that the function of these cavities was to convert the vital spirit (pneumazooticon), contained in the blood and coming from the heart, into animal spirit (pneumapsychikon), giving rise to thoughts and emotions [3]. It was Herophilus who described and defined the rearmost brain cavity (the fourth ventricle). This region was regarded as the command center of thoughts and emotions, and he compared its posterior wall to the reed pens that were used in Alexandria at the time, and thus emerged the name calamus scriptorius or calamus Herophili [4].

Claudius Galenus (ca. 129 – ca. 217), or simply Galen (Fig. 1.3), was one of the most important doctors of ancient times. Born in Pergamon, an ancient Greek city (now in Turkey), he traveled extensively throughout the Roman Empire, studying medicine. In 157, Galen returned to Pergamon, where he reached the position of physician for the High Priest’s gladiators, and he became one of the richest and most influential men in all of Asia. He spent 4 years in that position and provided very important observations about anatomy and surgery. He reported the wounds of the gladiators he treated as “windows into the body”. Needing to always keep gladiators healthy, as well as treat their injuries, he also highlighted the importance of diet, hygiene, preventive medicine, and exercise. He provided detailed knowledge about general and brain anatomy, which, unfortunately, came from dissections of monkeys or oxen, a fact which, curiously, was never mentioned in his works. Galen described the ventricles in considerable detail, as four cavities and their connections, two anterior, and two posterior (the third and fourth ventricles). He believed that the ventricles were responsible for storing the animal spirit (pneumapsychikon), which was regarded as the active ingredient for the brain and nerves. Although it was believed at the time that the ventricles, particularly the anterior ventricle, were the source of pneumapsychikon, Galen argued that the soul and the most important cognitive functions were located in the periventricular brain parenchyma. Such considerations are derived from his clinical observations at the gladiator’s school in Pergamon. He noted that when a traumatic injury affected the ventricles, death did not occur, even if sensitivity and strength were lost. Imagination, reason, and memory were regarded as the three constituents of the intellect, and it was thought that they could be affected separately. No illustrations of Galen’s anatomical observations exist, as he encouraged his students to seek knowledge by handling structures and not by making illustrations [5, 6].

The cerebroventricular doctrine of the time of Galen was followed by the development of the Cell Doctrine, a curious blending of classical Greek medical concepts with Christian ideologies. In the fourth century AD, the Byzantine physician Poseidon reconfigured the theories of Galen, probably being the first to report concepts of brain localization, stating that anterior brain injuries affect the imagination, medial brain injuries affect reason, and posterior regions, memory [4, 6]. At the same time, church officials, particularly Nemesius, Bishop of Emesa (ca. 390) and St. Augustine (354–430), sought to conceptualize the non-material nature of the soul. Little is known about Nemesius beyond the fact that he was a bishop, and that he innovatively attributed imagination to the connection between the cavity located in the frontal lobe and the five senses. The work attributed to him, De Natura Hominis, exerted a significant influence during the scholastic period, although many authors believe the work was written by St. Gregory of Nyssa. In fact, in many ways, the work has ideas that are similar to the thought of the great Nicene doctor. It is a book currently studied in Catholic theology, and is a remarkable work showing the concern of the Bishop of Emesa with the accuracy of the concepts. His way of accepting or rejecting the doctrine of the ancients reveals a person with great knowledge of secular authors. De Natura Hominis also contributes to the doctrine of the ventricular localization of mental functions. In fact, a doctrine was created, based on the Alexandrian and Galenic concepts, adapted to Catholic thought. An analogy was made with the Holy Trinity; hence, the division of the brain cavities into three cells. The Cell Doctrine remained in force throughout the Middle Ages. What are known today as the lateral ventricles were considered to be a single cavity, the first cell of which, in its anterior part, received external impulses and other impulses from the rest of the body, characterizing the reception of common sense (sensus communis). From this region, imagination (imaginativa) and abstractions (fantasia) were created, in the posterior part of the first cell. The second cell (now known as the third ventricle), or medial cell, was the site of the cognitive processes, such as reason (ratio), judgment (aestimativa), and thought (cogitativa). The function of the posterior cell (now known as the fourth ventricle) was changed from a galenic motor concept to the source of memory (memorativa) [6–8] (Fig. 1.4).

Albertus Magnus (ca. 1193–1280) (Fig. 1.5), also within Catholic thought, reinforced Cell Doctrine theory and believed that the brain functions were mediated by a system of ventricles or paired chambers. The front ventricles (sensus communis) were associated with the processing of the five senses. Images formed therein passed to the medial ventricles, the seat of reason (ratio) and thought (cogitativa), and the posterior ventricle, the seat of memory (memorativa) [9, 10]. These concepts remained as dogma from the Dark Ages to the Renaissance, when they began to be seriously questioned, as a result of more accurate anatomical descriptions. Interestingly, at the time there were only non-illustrated descriptions of the Cell Doctrine. The first known drawing of the brain illustrated a text from around 1250, from Salerno, by an unknown author (Fig. 1.6). The drawing is a full-body design with a representation of the thoracic and abdominal cavities, in addition to representations of the blood vessel systems [11, 12].

Still in the Dark Ages, it is worth highlighting Mondino de Luzzi (ca. 1270–1326). He was the first physician to officially receive authorization to perform dissections at the University of Bologna. His masterpiece, Anathomia Mundini, was completed in 1316. It was the first book in medical history devoted entirely to the structure and functioning of the human body, and was used for teaching anatomy for more than 200 years. Mondino personally carried out several dissections on human cadavers, but he also made use of a servant, called a barber, working under his orders (Fig. 1.7). With such work, many questions were raised about the works of Galen, the dogmas of the time. As a result, Mondino is considered the “restorer of anatomy.” The editions of Anathomia Mundini up to 1478 were only handwritten, but were printed from then on. This because of the invention of the printing press by Johannes Gutenberg (ca. 1398–1468) has ocurred in the 1430s, with the first incunable, the Gutenberg Bible, being ready around 1455 [9, 10]. In the Middle Ages, books had practically no illustrations, and so Anathomia Mundini did not have anatomical figures until the edition of 1521 [13–15] (Figs. 1.8, 1.9, and 1.10).

Guido da Vigevano (ca. 1280 – ca. 1349), great inventor, physician, and student of Mondino, also performed dissections on cadavers, and his manuscript, Anathomia, was published in 1345, showing an innovation at the time: the presence of anatomical illustrations [16, 17]. The work demonstrates, for the first time, in six plates, images of the head, brain, and spine. These images, although schematic and very rudimentary, were typical of medieval times, due to the lack of perspective in the drawings (Figs. 1.11 and 1.12). They can be considered as the first neuroanatomical drawings in history, and were the basis for the development of anatomical science in the Renaissance, during which time the ultimate conjunction between science and art took place, reaching its peak with the phenomenal Fabrica of Vesalius. [16–18].

Leonardo da Vinci (1452–1519) was the first person to combine the experience of an artist with a profound understanding of anatomy. From the newly introduced technique of the perspective derived from Filippo Brunelleschi (1377–1446), he outlined anatomical figures with extreme precision. Leonardo was a pupil of Andrea del Verrocchio (1435–1488), in Florence, the cradle of the Renaissance, where the perspective technique had been established. Although his work with brain illustrations did not have much influence on his contemporaries, Leonardo brilliantly united art and science, with masterly application of the perspective technique. Around 1487, Leonardo began to record his personal ideas and experiences with anatomy. In his nocturnal dissections, he found his way between the traditional scholasticism and the precise designs made from the direct visualization of anatomical parts. However, his first famous drawing of the brain was still based on the Cell Doctrine (Fig. 1.13). Only in the period between 1504 and 1510, during which Leonardo had his first experiences with ventricular wax injection, in animals such as oxen, or even in corpses, was it possible to view the ventricles as truly as possible (Fig. 1.14). Thus came about the first ventricular images in true perspective (Fig. 1.15) [19–22].

Despite this evolution in ventricular concepts shown by Leonardo at this time of transition in the Renaissance, there were still authors who blindly defended the Cell Doctrine (Figs.1.16, 1.17, and 1.18).

Other contemporary brain anatomists, such as Jacopo Berengario da Carpi (ca. 1460–1530) and Johannes Eichmann, also known as Johannes Dryander, or simply Dryander (1500–1560), succeeded Leonardo, and the work of these authors together provided a growing realism in graphic representation of the brain. The great precision of the illustrations was noted, arising from personal participation in dissections and due to the improvement in cadaverous fixation techniques [29]. Although the drawings of these two artists are not necessarily completely precise (the two artists are contradictory to some extent, since they still use some illustrations from the Cell Doctrine), such works solidified the decline, initiated by Leonardo, of the medieval concepts (Figs. 1.19, 1.20, and 1.21). In addition, these publications and illustrations laid the foundation for Vesalius to develop Fabrica. There is evidence that Dryander and Vesalius had contact with each other’s work. In the translation of Anathomia Mundini in 1542, done by Dryander, it is possible that he copied parts of the text of Vesalius of 1538, Tabulae Sex, angering Vesalius [30].

In 1543, the principal benchmark in anatomical history emerged: De humani corporis fabrica libri septem or De humani corporis fabrica, or simply Fabrica (Fig. 1.22), by the Belgian Andreas Vesalius (1514–1564), considered the “father of modern anatomy” [34]. He graduated in medicine from the University of Padua in Italy and in 1538 he published his first work: Tabulae Sex, a set of six anatomical drawings made by himself. Before Vesalius, very little had been discovered about anatomy and physiology since ancient times, when the findings were based on the dissection of animals. Vesalius, on the contrary, based his knowledge on human dissections of the bodies of executed criminals and victims of the plague. Vesalius was of humble origin, but after the publication of the Fabrica, he became very important. In 1546, he was appointed court physician of the Holy Roman Emperor Charles V and remained at his service until his abdication in 1556, thereafter serving Philip II, king of Spain. Fabrica is considered one of the most influential scientific books of all time, and stands out for its illustrations, some of the finest woodcuts ever made. Vesalius, with Fabrica, questioned a large part of the Galenic theories. To print the work, he spared no expense. He hired the best artists, including the German-born Italian painter Jan Stephan van Calcar (ca. 1499 –ca. 1546), a disciple of the Venetian painter Tiziano Vecelli (ca. 1488–1576), who made the prints in the first two parts of the work, as well as the great printer Johannes Oporinus (1507–1568), from Basel, to prepare the pictures to be printed. Vesalius ended up going to Basel to personally supervise the work. This work is a magnificent example of the best production of books in the Renaissance, with 17 full-page drawings, and several illustrations with text. Consisting of about 700 fine print pages, the book is divided into seven parts or “books” giving a complete overview of the human body. Book VII describes the brain and also presents fantastic ventricular images (Fig. 1.23) [35, 36]. Regarding this last part of his work, Vesalius said at the time:

“We have resected all the portions of the dural and the thin membranes which occurred in previous figures. Then we have removed in the sequence of dissection the right and left portions of the brain so that the cerebral ventricles now begin to come into view. First, we made a long incision along the right side of the corpus callosum where the sinus denoted by one of the M’s exists, which was led into the right cerebral ventricle. Next we removed the right part of the brain lying above the section where we cut the skull in a circular fashion with a saw. When we had finished the same on the left side, we placed here the left part of the brain so as to show, to some extent, the upper aspect of the left ventricle, while the corpus callosum still remained in the head”. [4]

After Da Vinci and Vesalius, various other authors focused their attention on smaller structures in the ventricular system, such as the union between the third and fourth ventricles, the cerebral aqueduct. Although initially described by Galen, it was better characterized during the Renaissance, particularly by Da Vinci, Berengario, and Vesalius, the most accurate, of course, being Vesalius [37]. In fact, one of the tutors of Vesalius, Jacques Dubois (1478–1555), also known as Jacobus Sylvius in Latin, was a famous French anatomist and fanatical follower of Galen, and had already carried out a detailed description of the aqueduct in his Isagoge, published in 1555. However, Vesalius, curiously, does not mention this description in his work. In 1663, a Dutch anatomist named Franz de le Boë (1614–1672) (Fig. 1.24) or, coincidentally, Franciscus Sylvius, in its Latinized form, also described the same structure in his Disputationes, published in 1663, and it is likely that the term ‘aqueduct of Sylvius’ is a reference to the latter, who also described the lateral fissure of the brain [38].

Despite the precise descriptions of the ventricular cavity made during the Renaissance, there was controversy over its true content. Vesalius, although having made detailed descriptions, still believed in the concept of antiquity that the ventricles were filled with air during inspiration, and that they contained the animal spirit (pneumapsychikon). This idea remained quite controversial at the time and divided different authors a great deal, and only after the discovery of cerebrospinal fluid (CSF) was such discussion put to an end. This discovery was made in 1764 by the Italian Domenico Felice Antonio Cotugno (1736–1822) (Fig. 1.25) who, besides giving a detailed description of the lumbosciatic pathway, also described the possible continuity between the ventricles and the subarachnoid space. This finding of continuity was later confirmed by the French neurologist and experimental physiologist François Jean Magendie (1783–1855) (Fig. 1.26), at the medial region of the fourth ventricle, now known as the foramen of Magendie or median aperture of the fourth ventricle. Magendie, among other contributions, introduced strychnine and opium in the practice of medicine, distinguished sensory and motor functions of the spinal nerves, and introduced the systematic use of laboratory animals in medical research [5, 39, 40].

The description of the interventricular foramen took place in 1783, and is credited to the Scottish physician Alexander Monro secundus (1733–1817) [5] (Fig. 1.27). Monro secundus provided detailed descriptions and illustrations of communication between the lateral ventricles and the third ventricle, now known as the foramen of Monro or the interventricular foramen, and also innovatively described anatomical changes related to hydrocephalus. Monro also helped to establish what is now known as the Monro-Kellie doctrine of intracranial hypertension [41, 42]. Following the descriptions of the ventricular details, the Czech anatomist Vincent Alexander Bochdalek (1801–1883) discovered the lateral recesses in 1849, but mistakenly thought they were blind extensions of the fourth ventricle, whereas they are actually communications with the subarachnoid space. This finding was made by the German anatomist Hubert von Luschka (1820–1875) (Fig. 1.28) in 1855, at the University of Tübingen. Such communications were known as lateral apertures of the fourth ventricle, or simply, foramen of Luschka [43]. von Luschka also confirmed the presence of the foramen of Magendie. His findings, though much questioned by his contemporaries, were later confirmed by many anatomists, including Key and Retzius in 1875 [44, 45].

Without a doubt, the main descriptions of the ventricles and CSF circulation terminate with the work of Axel Key (1832–1901) and Magnus Gustaf Retzius (1842–1919). In their work, which earned Retzius a seat in histology at the Karolinska Institute, they injected colored gelatin into corpses and showed that the gelatin flowed through the arachnoid granulations or villi, or Pacchionian granulations, to the superior sagittal sinus. The colored gelatin was also evident in the cervical lymph nodes [46]. This work presents beautiful images and shows extreme precision in the presentation of ventricular and subarachnoid space anatomy (Figs. 1.29 and 1.30).

Knowledge of the morphological aspects, anatomical in particular, of the ventricles is of paramount importance for the success of ventricular endoscopy. It is vitally important to have a thorough understanding of the lateral and third ventricles, the sites of most ventricular endoscopic procedures. During the embryonic period, the ventricular system appears in the fourth week, after neural tube closure, at which time the three primitive vesicles are formed: the prosencephalic, mesencephalic, and rhombencephalic, from rostral to caudal. In the fifth week of gestation, the prosencephalon gives rise to the telencephalon (brain hemispheres) and diencephalon. The mesencephalon remains unchanged, and the rhombencephalus gives rise to the metencephalon (pons and cerebellum) and medulla oblongata. Due to these changes, cavities are formed inside these vesicles, communicating with the lumen of the neural tube, and these vesicles are the beginnings of the future ventricles. The cavity of the telencephalon gives rise to the lateral ventricles. The third ventricle comes from the cavity of the diencephalon, and the fourth ventricle comes from the cavity of the rhombencephalon. The lumen of the mesencephalon connects the third and the fourth ventricles, becoming increasingly narrow, constituting the cerebral aqueduct of Sylvius. During this phase, ventricular expansion takes place from caudal to rostral, and is proportionally greater than the brain development [5, 47]. The exact position and spatial conformation of the ventricular system is genetically controlled. This information comes from studies on animals, mostly on chicken and zebrafish embryos. One of these gene controllers is the ventral neural indicator gene, Sonic Hedgehog (Shh), the products of which are secreted by the notochord. Early brain-notochord separation may result from loss of Shh expression, resulting in ventricular collapse of the surrounding tissue [5, 48]. Anatomically, the ventricular system is divided into four chambers that communicate with each other: the right and left lateral ventricles, and the third ventricle and fourth ventricle. The lateral ventricles are C-shaped cavities, situated deep in each cerebral hemisphere. Supposedly, this form is related to the embryonic expansion of the frontal, temporal, and occipital lobes, with the consequent downward and anterior displacement of the temporal lobe (Figs. 1.31 and 1.32).