Effects of trepanation on brain pulsations
Trepanation has profound impact on brain pulsations. The question as to whether the brain pulsates when the skull is completely closed and fully ossified, as it is known to do in open skulls, is one of the fundamental problems in the study of cerebral blood circulation. This question is of prime importance, and on its answer will depend the entire approach to all similar problems. It will be clear from our further exposition that all investigators advancing their specific theories on cerebral circulation were first required to take a stand precisely on this problem. The disputed question as to whether or not the brain pulsates within the closed cavity of the fully ossified skull was broached already 300 years ago in the literature, and was until recently still a controversial problem.
Cerebral pulsations in conditions of impaired continuity of the skull are so obvious that they may be detected by any observer. The first views on the causes of cerebral pulsations may be found in the works of Galen (1131-201 A.D.) whose observations were based on in vivo observations in animals. He suggested that brain pulsations were directly related to the respiratory rhythm, and were due to seepage of air into the cerebral ventricles through the cribriform plate. He also considered brain pulsations to be possible because of the existence of a vacuum between the cerebrum and the dura. Oribasius, who compiled Hellenic and Roman medical studies, also mentions, some two centuries after Galen, the pulsations of the brain observed by him in newborn and adult human and animal subjects with incompletely closed skulls. Oribasius ascribed the pulsatory movements of the brain to respiratory movements and to the rhythm of cardiac contractions. An entirely different view on the pulsations of the brain was subsequently expressed by Fallopius (1562). This scientist did not observe any pulsations of the brain in his studies.
Later, Vesalius (1600) wrote on the movements of the brain in newborn babies and adults who had sustained cranial injuries and on animals whose skulls were opened in vivisection studies. The brain movements were ascribed to the pulsations of the arterial branches of the dura. Vesalius equated the movements of the brain to those of the dura. There were many adherents to Vesalius' point of view, as well as many opponents. Vesalius' followers, among whom were Pacchioni and Baglivi, further developed his teachings and studies on the dura mater, which they considered as a type of muscle or even as the heart of the brain, responsible for its pulsatory movements. His opponents, on the other hand, refuted his claim of the participation of the dura mater in the pulsatory movements observed. Schlichten (1750) thus thought that these brain movements were due to its swelling following the increased blood content following each pulse wave. Some, like Galen, considered brain pulsations in the closed skull to be possible, by assuming the existence of a hypothetical vacuum between the cerebral surface and the dura mater.
The observed sucking in of air through a small trephine opening in the skull during inspiration and its expulsion during expiration was, according to Schlichten, confirmatory of his point of view. As an indirect proof of the existence of this vacuum Schlichten gave the constant presence of extravasates in the cranial cavity of dogs killed by a blow on the skull. At the same time there was another explanation for these brain pulsations. Senak (1749) ascribed them to changes in the caliber of the large arteries at the base of the brain. He maintained that the arteries dilating in systole increased the mass of the brain, while their constriction in diastole was manifested by a relaxation of the brain. It should also be noted that Ravina (1811) in his experiments noted the presence of brain pulsations through a cylinder fixed to the skull. Ravina filled this cylinder with water, and gauged the movements of the brain by observing a float which he put on the surface of the water column. Ravina thus concluded that brain pulsations did exist in mammals.
After the discovery of the cerebrospinal fluid in which the brain substance bathes, however, the problem of the existence or absence of brain pulsations was approached in an entirely different light (Contugno, 1864; Magendie, 1825). It then became clear that the space between the surface of the brain and the dura mater which formerly was thought to be filled with compressible air, was actually filled by the incompressible cerebrospinal fluid. The views on the causes for rhythmic alteration of the brain volume also changed. Magendie (1834) assumed that pulsations of the brain were possible because of the transfers of the fluid discovered by him. This mechanism was in his view also related to inspiratory and expiratory movements. In inspiration, a venous stasis of the extremely distensible spinal venous plexuses occurs, which leads to the expression of cerebrospinal fluid into the cranial cavity. The intracranial volume of cerebrospinal fluid increased in this way also swells the brain. In expirium, however, the process was seen to follow a reverse course, i.e., the cerebrospinal fluid flows out from the cranial cavity into the spinal canal, and the brain relaxes. A review of the work of different investigators published during the past century shows that some of them were able to solve the problem as to whether brain pulsations exist in the closed skull cavity, as long ago assumed by Galen and Schlichten. Such a process was possible only when one assumed the existence in the brain of a space filled with air, allowing for alterations of the cerebral volume.
When the cerebrospinal fluid was discovered, it was recognized that the cranial cavity was completely filled and the point of view that cerebral pulsations in the hermetically closed skull were not possible also appeared in the literature. This, for instance Muller (1839) and Bourguignon (1839) were of the opinion that cerebral pulsations did not exist. An attempt to support this view experimentally was made by Pelehtan. Into the skull of a dog he inserted a glass tube on the tip of which there was a stopcock. The hermetically inserted tube was filled with water. On opening the tap, communication was allowed between the cranial cavity and the atmospheric air. In these conditions any movements of the water column observed in the tube would indicate the presence of brain pulsations. The movements of the water column, however, immediately stopped on closing the tap; in other words, they disappeared on reinstating the hermetic conditions existing within the skull cavity. Bourguignon obtained similar data in his experiments carried out in 1839. He constructed a special instrument called the "encephalokinoscope". This consisted in a tube screwed hermetically into the skull. The tube was filled with a tap and an angled lever which moved on a horizontal axis. The short horizontal arm of the lever was filled with a membrane which was placed on the dura mater.
The long vertical arm of the lever served as an indicator of movements taking place on the dura which it amplified many fold. As earlier investigators, Bourguignon also observed movements of the membrane in conditions of open skulls. When the connection of the skull cavity with the atmospheric air was interrupted by closing the tap, these movements stopped. The absence of pulsatory brain movements in the closed skull was even more forcibly demonstrated by Donders in 1851. Donders inserted collodium plastic windows into trephine openings of rabbit skulls, and through these was able to observe at length the exposed cerebral surface. He failed to observe any movements even under X45 magnification of the cerebral surface under these conditions. Brain pulsations were not detected even in forced inspiration and expiration, or in Valsalva's procedure. Ehrmann failed to observe any brain pulsations in the completely closed skull into which he inserted a copper cylinder closed on the side adjacent to the brain by a magnifying lense. These findings were corroborated in the studies of a whole series of researchers (Kussmaul and Tenner, 1857; Akerman, 1859; Leyden, 1866, and others). It may therefore be concluded as an established fact that no pulsatory movements of the brain exist in the completely closed skull cavity. It would be appropriate perhaps to cite Leyden, who wrote in this regard in 1866: "At the present time almost all physiologists are convinced that the brain does not pulsate in the close skull" (p. 114, cited from Althan). This point of view was finally best expressed in the so-called Monroe-Kelly theory; the widely accepted theory bearing the name of these authors is based on the premise that no cerebral pulsations exist in the closed skull. On the other hand, these authors advanced their theory of the constancy of blood volume contained in the brain which in our mind is an entirely indefensible position. According to the Monroe-Kelly theory, the fact that the cerebral substance is incompressible would indicate the invariably equal blood content of the cerebral vessels, regardless of changing physiological or pathological states of the cerebral substance at a given moment. Indeed, this assumption on the consistency of cerebral blood volume is the weak point of the theory, and was subjected to criticism by several investigators (Burov, 1846; Donders, Kussmaul and Tenner; Akerman and others).
The inconsistency of this postulate of the Monroe-Kelly theory that the blood volume contained in the brain was constant, became immediately obvious in experimental work. Thus Donders, in observing the vessels of the pial membrane through a "window" inserted into the skull, noted that the vessels dilated if the breath was held in inspirium. Kussmaul and Tenner observed an extreme degree of cerebral ischemia in animals killed by exsanguination. On the other hand, congestion and hyperemia of the cerebral vessels was observed in animals who died from strangulation. Akerman also observed a marked vasodilatation of the pial vessels when the respiratory passages of the experimental animal were occluded, and a reversal of the pial vessels to their initial size after allowing renewed free access of air. There series of experiments provided data which clearly indicated that the cerebral blood volume altered drastically together with changes in caliber of the blood vessels in the closed skull, and showed the absence of cerebral pulsations. It was then necessary to clarify why alterations in cerebral blood volume did not cause alterations in the volume of the brain itself. A definite answer to this question was not provided at the time. The possible answers are as numerous as the investigators who were ready to supply them. Akerman, for instance, thought the changes in the pial arterial vessels to be insignificant, so that no pulsations could result in the brain as a whole. Donders and Berlin, on the other hand, concluded that the absence of cerebral pulsations was due to the fact that the increased intracerebral blood volume was counter-balanced by cerebrospinal fluid compression. Decreased cerebral blood volume on the other hand, would cause an increased transudation of fluid, and an alteration in the blood cerebrospinal fluid ratio, thus compensating for the increased blood volume. The hypotheses of these authors assumed the very rapid absorption of cerebrospinal fluid during systole, and its no less rapid transudation in diastole. Akerman and Althan, however, took issue in 1871 with Donders' highly speculative conclusions and stated that logically the reverse process would be expected. According to Akerman and Althan, it is more correct to assume that during systole blood plasma passes through the capillary wall, while interstitial fluid is reabsorbed within the vessel during diastole. A somewhat different explanation was advanced by I. Navalikhin in 1874. This author claimed that alterations in cerebral blood volume were not manifested by brain pulsations in cases of pressure increase inside the skull. This was also proved inconclusive by Grasheim, who showed in 1887 that the compressibility of the cerebral substance was even lower than that of boiling water. According to this author, the force necessary to compress the brain is so enormous that it could not possibly be attained in the physical conditions existing within the cranial cavity. It may thus be said in conclusion that the absence of cerebral pulsations in the hermetically closed skull, is, at present, a firmly established fact. Pial arteries were also noted to alter their diameter in response to blood volume changes. It is not yet clear how the brain maintains its constant volume in spite of a rather wide range of changes in blood volume within the fully closed cranial cavity. The so-called theory of Monroe-Kelly-Burov is based on the premise that since three incompressible components are contained in the cranial cavity (nervous tissue, cerebrospinal fluid and blood) the ratio between blood and cerebrospinal fluid must constantly alter in order to maintain a physiologically balanced state. Unfortunately, however, the mechanism of this regulation of volume has not yet been found. It would be incorrect to maintain that all investigators of the 19th century who studied cerebral circulation supported the view confirming the absence of cerebral pulsations in the hermetically closed skull in adult blood circulation, subscribed to the opinion expressed by authors who believed that cerebral pulsations did exist in the closed skull cavity.
Many authors, such as Althan, strongly maintained their convictions, although this was unsupported by experimental data, and drew conclusions only from deductive, logical thinking or as a result of criticism of experiments carried out by other authors who, by the way, may have maintained an entirely different point of view. On the other hand, in 1881 Mosso drew the entirely unjustified conclusion based on many observations and factual material obtained in various experiments and on individuals with skull defects, that cerebral pulsations must also be present in the intact skull. It should finally be mentioned that a similar point of view was also maintained by the Russian scientist Nagel (1889). Although he did not completely reject the experimental data indicating the absence of cerebral pulsations in the closed skull, Nagel nevertheless settled for a compromise solution. He considered cerebral pulsations to be absent only in those parts of the brain which were tightly adherent to the dura mater, and thus to the skull. In this author's view, however, pulsatory movements were possible in these parts of the brain which were not in close contact with the dura mater. In other words, while some parts of the brain were completely immobilized following their contact with a resistant surface, other parts of the brain on which no pressure was exerted could change their volume at the expense of the space filled by the cerebrospinal fluid which communicated freely with the spinal cavity. Adherents to the theory supporting the existence of brain pulsations in the closed skull have thus settled for a compromise solution in order to account for contradictory experimental evidence. In fact, although it proved impossible to demonstrate the existence of brain pulsations in hermetically closed skulls, certain followers of this obsolete theory would nevertheless attempt to prove the existence of pulsations in that part of the brain which is not intimately adherent to the dura mater, especially in the occipital region. Leyden (1866) already expressed his opinion, widely accepted by most of the physiologists and physicians of his time, that no brain pulsations existed in hermetically closed skulls, but in the 20th century only a minority of investigators adhere to this viewpoint. This change in concept could undoubtedly be ascribed to the development of neurosurgery from the beginning of the 20th century.
The more extensive application of brain surgery aided in direct observations of the exposed cerebral surface which became possible for a larger number of investigators. It was seen that on exposing the brain, the most striking feature was the appearance of pulsatory movements of the brain corresponding to the cardiac beat, and a tide-like movement of brain swelling and receding, corresponding to respiratory movements. In fact, an absence of brain pulsations in the opened skull is serious indication for the neurosurgeon of the presence of some pathological process, whether it be a brain tumor, and abscess, or a sign of acutely increased intracranial pressure. These brain pulsations were assumed to exist in closed skulls as a matter of course. No further experimental confirmation of this was regarded as necessary. Understandably this general belief predominates in the literature on the subject. As already mentioned, those investigators in the 19th century who attempted to ascertain whether brain pulsations existed in the closed skull, obtained negative results. With different experimental techniques in the 20th century, this has changed. Present theories of cerebral blood circulation hold the basic premise that brain pulsations exist even when the skull is completely closed. This has, however, neither been fully demonstrated nor experimentally confirmed. Thus, for instance, Sepp's theory expounded in his monograph in 1927 is based on three main fundamental factors. The first postulates a special structure for the cerebral capillaries, which he believed, contained an elastic layer. This, however, would exclude any possibility for the lumen of the cerebral capillaries to alter. It would thus refute the factual data obtained in the mid-19th century, which indicated that in different physiological and pathological conditions the cerebral vessels constrict or dilate. Sepp's theory was found to be inconsistent in this respect in later studies of histologists and physiologists, who demonstrated the absence of any elastic membrane of the cerebral capillaries and who again demonstrated their ability to change their lumen within a wide range (see the works of Snesarev, Anokhin, Klosovskii, Forbes, Cobb and others). The second premise in Sepp's theory was the acceptance of the existence of brain pulsations in the closed skull. In this regard also Sepp failed to see the necessity of corroborating his assumption by experimental studies, or to subject it to critical analysis in the light of experiments confirming a viewpoint opposite to his own, carried out a long time before he formulated his theory. He insisted on this point in spite of the fact that for almost half a century before his time the absence of brain pulsations in the closed skull was irrefutably demonstrated in experimental work of other investigators. As a third fundamental premise of his theory Sepp postulated that the cerebrospinal fluid participated in the nourishment of cerebral tissues. He claimed that cerebrospinal fluid flowed in special vascular plexuses towards the subarachnoid space, from where it supplied the brain tissue under the pressure of the pulse wave. He assumed that cerebrospinal fluid entered the cerebral substance through precapillaries, and was reabsorbed by the postcapillary venules in the blood vascular bed. Sepp thought that only a gas exchange occurred at the level of the cerebral capillaries. This third premise in Sepp's theory is of course completely inconsistent in the light of present knowledge. As to his first postulate, it is well known that cerebrospinal fluid nourishes the cerebral tissues only at a certain stage of phyletic and ontogenetic development. In the adult, however, the cerebrospinal fluid does not play an appreciable role in the nourishment of cerebral tissues, whose activity is insured by the supply of nutrients through the blood (Klosovskii, 1947). As to his second premise, it is difficult to imagine that such a complex process as the infiltration of cerebrospinal fluid into the cerebral substance would be effected merely by mechanical factors, such as the propulsion of cerebrospinal fluid into the brain by the pulse waves. This can be realized only if brain pulsations in the close skull are possible, an assumption which Sepp in no way corroborated.
The functional division of the cerebral blood bed into precapillaries destined for cerebrospinal fluid circulation and capillaries exclusively reserved for gas exchange is of course unacceptable with our present knowledge. Sepp's claim of the presence of elastic membranes in the cerebral capillaries was also without foundation. Obviously Sepp's concept on the pulsations of the brain in the closed skull were the product of pure speculation, and served only to support his theory. In spite of this fact we see that this view is also held by Pfeifer (1928-1930). The latter attempted, on the basis of anatomical data on the angioarchitectonic structure of the brain to create an entire trend of teaching on cerebral blood circulation. He thus divided the cerebral blood circulation into three parts. The first of these, "the derivative part" in Pfeifer's terminology, deals with blood supply to the different brain regions. The "nutritive division" of the cerebral blood circulation consisted in that part of it engaged in the transfer of gases and in the transudation and resorption of fluids. The third part deals with the regulation of cerebral blood circulation, and was given special attention by Pfeifer. This last part of the cerebral blood circulation regulates fluctuations in blood pressure, and governs the blood flow rate in the cerebral vessels. It has special arrangements linking the derivative and nutritive divisions of cerebral blood circulation. Such special linking structures Pfeifer named the so-called "Saugarterien, Druckvenen" and "Drosselsthcke". While Pfeifer thus tended to accept the existence of cerebral pulsations which were synchronous with the pulse wave and respiration, he also, on the other hand, postulated the existence of a whole series of special arrangements safeguarding an uninterrupted blood flow to the brain. Pfeifer (1928-1930), like Sepp, postulated the presence of elastic membranes in the cerebral capillaries, and regarded the cerebral capillary network as a rigid system of porous tubes. In a special chapter in his monograph, published in 1928, which deals with the possible changes which capillaries may undergo during brain pulsations, Pfeifer draws an analogy in maintaining that the capillaries behave in a way similar to that of the carotid arteries in backward expansion of the head or when it inclines forward. In other words, during brain pulsations the capillaries distend or contract only in a linear, longitudinal direction. Together with the hypothesis of this author, who considered the existence of brain pulsations in the closed skull as an established fact, there were also other theories similar to those expounded by Nagel in his time. Hhrthle maintained in 1927 that since the capsule enclosing the brain is non-expandable, the cranial cavity contains a number of foci capable of absorbing the increased expansion of the brain in raised intracranial pressure due to an increased blood content in the cranial cavity. The suboccipital membrane, venous lacunae of the dura, and venous plexuses in the spinal canal were considered as such pressure- absorbing foci. The cavity enclosing the central nervous system may increase in capacity when the brain is congested with blood at the expense of blood expelled from the venous plexuses of the spinal canal and by distending the suboccipital membrane. On the other hand, the brain was never seen to pulsate when observed through hermetically sealed "windows". The well-known works of Forbes and Cobb, who in their laboratories investigated the reactions of pial arteries to different factors, are interesting in this respect. Variations in the experimental setup enabled us to conclude that the pial vessel diameter altered within a wide range, in spite of the absence of any detectable brain pulsations. In this connection we would again like to mention the experiments made by Clark, who observed the pial vessels of rabbits through plastic windows hermetically screwed into their skulls. These authors made their observations during a period of a few months, and did not observe any noticeable brain pulsations. We also used this method of hermetically inserted skull "plastic windows" in our work in studying the different aspects of cerebral blood circulation. We were repeatedly convinced in the course of our work that the hermetically closed skull was a determining prerequisite for the absence of brain pulsations. We also noted that whenever continuity of the skull was impaired, brain pulsations appeared which were coincidental with respiratory movements and cardiac rhythm. This relationship was observed in anesthetized animals, and in experiments when no narcotics were used. The cerebral movements were seen to cease immediately when the trephine opening was closed by a window, or, as in our experiments, when the microscope lens sealed the skull opening, and a hermetic closure of the skull cavity was obtained by additional application of bone wax to occlude the narrow gap remaining between the microscope tubus and the margin of the bone defect. It is well known to any researcher working with the window technique that the brain is never in contact with the window or microscope lens, and that there always remains a space filled with cerebrospinal fluid. In other words, the lack of brain pulsations in these cases does not result from the pressure exerted by the window or the microscope lens on the cerebral surface, i.e., it does not disappear following mechanical pressure. The cerebral surface can be tightly pressed against the "window" only when a sudden cerebral edema or brain swelling occurs. These may occur in disturbed venous blood outflow from the cranial cavity following compression of the arteries supplying the brain, or as a result of impaired cardiac activity. Disorders in fluid balance of the nerve tissues may also develop when veins or sinuses are injured during the preparations of "windows", or in injuries to the brain substance itself. If necessary precautions are taken to avoid any impairment of normal blood circulation to the brain, then cerebral edema and brain swelling will never develop. As already mentioned, a space exists between the "window" and the cerebral substance, filled with cerebrospinal fluid. In experimentally induced brain collapse the cerebral surface is seen to retract at distance of about 3 mm from the inner table of the skull. The brain then lies freely within the cranial cavity. However, even in these conditions no pulsations are seen on the brain surface. As already pointed out, we did not limit ourselves to the preparation of only one skull window, but in most of our experiments we inserted two such windows in two separate brain regions, for more extensive observation of the pia. Since during these procedures the outflow of a large quantity of cerebrospinal fluid could not be avoided, it was necessary as a counterbalance to inject an equal amount of saline into the skull opening. It was thus ascertained that the cerebral surface was not in direct contact with the window surface. The brain thus lay freely within the fluid-filled subarachnoid space, and its surface was separated from the skull and the surface of the windows by a layer of saline. In these conditions, too, no brain pulsations were noted. The objections of those authors (such as Alov, 1949), who claimed that the absence of brain pulsations in the experimental "window" setup were due to direct, mechanical pressure on the cerebral surface, are not valid. Such a possibility of error is very unlikely at the present level of technical perfection with which these experiments are usually carried out. It may be considered as firmly established that the brain does not pulsate in the hermetically sealed skull. If, however, the experimental technique is not scrupulously adhered to, one can see that it suffices to leave an even slight open slit between the bone and the window in order to note the brain pulsations which are so well known to occur when the skull cavity communicates with the air outside. Since the "window" technique limits the possibilities for observation only to a small brain area, we resolved to perfect a technical procedure for substituting the entire calvarium of the skull with a transparent roof. An indispensible condition for this experimental procedure was to reestablish a hermetical closure of the newly-formed cavity. In this way we hoped not only to extend the field of observation, but also to be able to throw some new light on the 300-year old dispute raging over the controversial problem on the behavior of the brain in the hermetically closed skull. From the many materials used in plastic skull repair we chose the allo-plastic substance as the most suitable for our purposes. An important advantage of this plastic material is that it does not irritate the skin, towards which it behaves as an indifferent material provoking minimal reactions of the surrounding tissues. Among the plastic substances investigated in our experiments, the most suitable proved to be the clearly transparent plastic polymethylmetacrylate compound. In our experiments we most often used ready-made plates of this plastic substance, known industrially under the name of organic glass or plexiglas, which we subsequently modeled into suitable forms for our "transparent skulls". In contrast to the materials used in plastic surgical repairs, such as tantalum, ticonium, stainless steel, vitalium or the plastic substance AKR-7, plexiglas is clearly transparent and was obviously excellent for our experiments. Plexiglas can be easily polished, and when heated it is malleable and can easily be modeled into the desired form, and then left to solidify by cooling. Plexiglas was the most suitable substance for the construction of an artificial skull which was exactly adapted to the size and the form of the bony calvarium removed, in order to create the necessary conditions for our experiments in a hermetically sealed skull cavity.* In addition to the advantages enumerated, plexiglas also has the advantage of being resistant to acid or basic corrosion, of being permeable to ultraviolet and roentgen rays, and of being resistant to bacterial activity. Furthermore, organic glass does not dissolve like cartilage or bone. The only inconvenience in the use of plastic glass consists in the reaction which develops in the dura mater and pia-arachnoid membranes in contact with it. Our observations have, however, shown that even this tissue reaction to the "transparent" skull is slighter than the tissue reaction to other materials, such as the plastic substances AKR-7 used for covering bone defects in neurosurgical practice (Leibzon and others). On the other hand, the absence of undesirable results in skull defect covers of metal or plastic substances in use in neurosurgery allowed us to hope for similar favorable results in substitution of the skull roof with a plastic cover. Similar attempts to prepare experimental animals with "transparent skulls" were carried out by Pudenz and Shelden (1944, 1946). Their experiments were carried out on primates, for the purpose of noting the changes taking place in the brain following head injury. Their first report appeared in 1944, and dealt with the technical aspect of the procedure necessary in replacing extensive skull defects with a plastic substance. These authors made two large trephine openings in both sides of the skull. A large bony ridge which covered the sagittal sinus and the bridging veins completely was left in the midline. According to Shelden, these primates with large plastic "windows" survived the procedure for over two months. It is to be regretted, however, that no information was given on the behavior of these monkeys during the period when they were fitted with such "plastic transparent skulls". Furthermore, no information was supplied on the condition of the brain under the plastic windows, nor was any information given on the state of the brain tissues on post-mortem examination, if such was carried out. Their work was illustrated mostly with drawings, and contained only one photograph representing the general view of the "plastic skull". No photographs were given in their report which was published two years later, with the exception of photographs of brain sections, and the main points in the author's work are illustrated only by drawings. The lack of any photographic documentation of the condition of the animals following surgery, and the failure of the authors to supply clinical descriptions of the condition and behavior of their experimental animals, deprives us of the possibility to draw conclusions on the value of their surgical technique in further physiological experimentation. The purpose of Pudenz and Shelden's experiments was to follow the directional displacement of the brain within the closed skull cavity, and the gross disturbances of cerebral tissues after skull injuries. In the report on our method we set for ourselves a much wider scope of perspectives of an entirely different character. For us the animal with a transparent skull was a rewarding subject for observation of the blood circulation in the arteries and veins of the pial network in conditions as close to normal as possible. The transparent skull enabled us to follow the blood circulation in the pial vessels during rest and in emotional excitation of the experimental animal. In using this method we followed objectively the character of the reaction of the pial vessels in different experimentally induced conditions of the brain. By replacing the bony calvarium with a transparent plexiglas roof we could follow directly the reactions of pial vessels to different drugs and various substances introduced into the blood stream or into the subarachnoid space. One of our main purposes was also to follow the development of the animal brain under the transparent skull during the first months of life (transparent roofs were fixed into the skulls of 1.5-2-month old puppies). It should be pointed out, however, that only a part of all these research projects in connection with these experimental procedures was carried out until now. It was clear from the very outset that on the solution of the nature of behavior of the brain in the closed skull depended a whole series of problems connected with cerebral blood circulation. We shall now give further details of our experiments intended to ascertain the presence or absence of brain pulsations in closed skulls. Replacement of the bony skull with a plastic roof is carried out after removing the calvarium, including that part of skull lying over the sagittal sinus. Our task was greatly facilitated by developments in surgical approach through the corpus callosum to the lateral and third cerebral ventricles (Klosovskii, 1948). Our experimental method for substituting the calvarium with transparent roofs was worked out in collaboration with V. M. Balashov. Cats and two-month old puppies with well developed, rounded skull vaults were used in our experiments. The surgical procedure for replacing the calvarium with plexiglas may be subdivided into two main parts. In the first stage of the operation the calvarium was removed from the anesthetized animal and a plaster of Paris mold of the dura-covered brain was taken. For this purpose the temporal muscle was carefully separated with the periosteum from its insertion points on the frontal, temporal and occipital bones of the skull, without injuring it. Both hemispheres were then exposed by removing the parietal bones together with the upper parts of the temporal squama and the posterior part of the frontal bones, as shown in Figure 163. At this stage of the surgical procedure the blood vessels should be carefully coagulated with the diathermy needle and bleeding from the bones stopped with bone wax. A cellophane sheet is placed on the dural surface after removing the bone, as indicated above, in order to separate the dura from the temporal muscles and to avoid any possible lesions. The skin is then carefully sutured. In order to avoid cooling of the exposed brain, it is always advisable to make generous use of thick cotton pads in dressing the head wound. The head dressing is then fixed in a thin plaster of Paris cast. This elaborate head dressing proved to be indispensible not only for avoiding any possible cooling of the brain, which may result in pial vasoconstriction, and to avoid any possible injury or pressure to the brain, but also to prevent any attempt of the animal to remove its head dress. After 5 to 7 days the second stage of the operation-fixing of the plastic cover on the skull is undertaken. During the period between the first and the second stages of the operation a plexiglas roof is carefully modeled according to the plaster of Paris cast model of the brain surface. The usual technique used in dental work was employed for that end. Particular attention should be given to polish the cover thoroughly, since the clarity of observation of the pial vessels depends to a high degree on its carefully polished surface. At the second stage of the operation the dura mater covering both cerebral hemispheres is turned down. In so doing, a longitudinal band of the dura about 3 mm wide is left in its place on the sagittal plane along the entire length of the sagittal sinus. Following this procedure, the transparent roof is firmly fixed with dental cement to the basal part of the skull which remains after the craniectomy. The layer of dental cement also serves to fill up any possible irregularities on the surface of the bone in contact with the rim of the plastic dome, thus ensuring the hermetic sealing of the skull cavity. Further stability of the "transparent skull" is ensured with 4 silver screws tightly screwed in the bony rim. Two holes are usually bored into the uppermost convexity of the "transparent roof", which are then hermetically closed by two chrome-plated or silver screws. The arrows on (Figure 164, a,b) indicate these screws. These openings were made into the transparent roof of the skull with a special purpose. Through them it was possible to rinse the cerebral surface, and to introduce different drugs or pharmacological substances into the cranial cavity. The skin at the rim of the transparent skull is then carefully excised. The skin wound is treated with antiseptic solutions according to accepted principles of general surgery, and with applications of a sulfidine emulsion. Prophylactic injections of penicillin were also given. Then the head of the cat or dog with the "transparent skull" was dressed after covering the transparent roof of the brain with a black paper, in order to preserve it from the effects of strong light and ultraviolet rays. The animals felt well already a few hours after the operation: they ran around, they drank milk and accepted fluid food. On the day following the operation they were indistinguishable (except, of course, for their head dressings) from the control animals running around the laboratory. The general good condition and emotional stability of the post-operative dog shown in Figure 165 (1,2,3,4) are clearly seen. We have at present in our laboratory several cats and dogs which live perfectly well with their "transparent skulls" for a period of 2 to 2.5 months after the operation. Thus, in fixing a "transparent skull" tightly cemented with dental cement and screws to the basal part of the skull we reconstructed a hermetically closed cavity. The brain was kept in physical conditions as close to natural as possible. In all cases a space between the plastic "transparent skull" and the surface of the brain remained, which in some cases was a mere slit, while in others it measured 3-5 mm in depth. This space was filled during operation with saline, which was later replaced by cerebrospinal fluid, all possible remaining air in the cavity being subsequently gradually absorbed. In this experimental procedure brain pulsations became immediately noticeable when the hermetically closed cavity of the "transparent skull" was opened by removing one of the two screws sealing the holes at the convexity of the plexiglas roof (Figure 166). The amplitude of pulsations was seen to depend on the depth of respiratory excursions, and on the force of cardiac contractions. The brain was noted to heave and slump coincidentally with the cardiac and respiratory rhythm. The sagittal sinus and the bridging veins were congested with blood at each expansion of the brain and emptied when it receded. It may therefore be deduced that expansion of the brain due to swelling with each pulsation is due to arterial blood filling at each pulse wave in systole and to impeded venous outflow due to interrupted flow of venous blood during systole in the atria of the heart. During diastole, on the other hand, the brain relaxes following renewed venous outflow to the heart, while there is no arterial blood inflow to the brain during diastole. It should be noted, furthermore, that the pulsations are clearly observed only in the superficial cerebral veins. Distinct arterial pulsations can be seen only in strong cardiac contractions, or in deep respiration. As is known, pulsations of the pial arteries over the cerebral hemispheres and in the posterior fossa are often clearly visible during surgical procedures on the human brain. Characteristically, however, the arteries of the posterior cranial fossa do not actually pulsate but have a wriggling, snake-like movement, changing their tortuous course. This change of contour at each pulse beat is clearly visible in the posterior inferior cerebellar artery, which, after leaving the vertebral artery, courses in meandering loops for a length of 2.5 cm in the subarachnoid space. Here, therefore, the brain pulsations seen on opening the skull even slightly, occur with longitudinal rather than caliber changes of the arteries. Movements of the brain due to its pulsation in the open skull undoubtedly influence the intracerebral vessels and capillaries. However, only indirect information can be collected on the changes taking place in the intracerebral capillaries with brain pulsations. We could establish in our studies on different experimentally induced conditions of the cerebral tissues, that in a large number of our specimens the capillaries were very tortuous. Tortuosity of the capillaries is also observed in different types of cerebral ischemia. The capillary network of the brain exposed by trephination in dogs killed by strangulation is a good illustration in this regard. Thus it is clearly visible in Figure 167, a that a capillary wall has lost its normal tonus, and the capillaries have shrunk and become tortuous. Capillaries in ischemic regions following arterial occlusion as well as in total brain ischemia due to ligation of the carotid and vertebral arteries present a similar picture (Figure 167,b). A similar capillary tortuosity, (as shown in Figure 167, c) is also observed in edema of the nervous tissues, i.e., in brain swelling or edema in hydrocephalus, or in all cases when blood flow within the capillaries is impeded by swelling of the surrounding tissues. It becomes evident from a comparison of the capillaries in these pathological conditions with those in the brain of normal dogs (Figure 167,d) that in pathological conditions the capillaries may become tortuous and contract in length. It might be assumed, therefore, that the same changes take place in the capillaries during increase in brain volume in systole, and in its decrease in diastole in the open skull. This process seems to us to be more probable than the one proposed by Pfeifer, who maintained that the capillaries elongated during swelling of the brain in systole at the expense of their walls which became thinner, and not as a result of unwinding and straightening of their spiral tortuosity, as we thought. On the other hand, Pfeifer thought that in diastole and during the resulting relaxation of the brain the capillaries were forshortened, and their stretched walls became thicker. We, however, thought that capillary contraction seen in brain pulsations in the open skull is due to their increasing spiral-like tortuosity occurring together with a change in diameter. Brain pulsations were never observed in animals with hermetically closed "transparent skulls" (Figure 168). This was true not only when the animals were at rest, but also when they were emotionally excited. Confirmation of our statement was obtained not only on direct observation through the transparent vault of the skull, but also in studies with the capillaroscope. Obviously, therefore, the absence of brain pulsations in the completely closed skull is a fact proved beyond any possible doubt. We went a step further, in order to obviate any possible future objections similar to those voiced by Nagel. For this purpose we carried out a specially designed experiment. As is known, Nagel raised the objection that although brain pulsations may be absent in the closed skull in the immediate vicinity of the rigid bone of the skull, they nevertheless do occur at the level of the soft cerebral membranes. The cranial contents - the cerebral tissues, the blood and the cerebrospinal fluid - are incompressible. However, cerebral tissues can swell, and the cerebrospinal fluid may be transferred from one place to another. Hence, in increased blood pressure at an average of 30 mm, as happens in systole, an increased intracranial pressure and a shift of cerebrospinal fluid may be expected to occur. In such a case the cerebrospinal fluid must be transferred from the cranial subarachnoid space to that of the spinal canal. The membranes enclosing the subarachnoid space within the spinal canal, yield in some areas to increased pressure. An increased inflow of venous blood from the spinal venous plexuses compensates for the increased pressure of the spinal subarachnoid space. On the other hand, such a transfer of cerebrospinal fluid from the cranial cavity into the spinal subarachnoid space would take place only if the intracranial pressure measurably fluctuated in each systole and diastole of the cardiac muscle. Our work with Kosmarskaya (1949) on the physiological features of cerebral blood flow in closed and open skulls showed that there was a distinctive difference in amplitude of the pulse wave in the vessels of the body and the arteries of the circle of Willis. Figure 169 shows the tracings of the pulse wave amplitudes recorded from the femoral arteries and from the cranial part of the common carotid artery of the dog. The latter reflects the amplitudes of the pulse waves within the arteries of the circle of Willis. The remarkable difference in pulse wave amplitudes recorded from the arteries of the limbs and the circle of Willis is an indication of the considerable changes exerted on the blood flow before it is allowed to reach the intracerebral vessels. A whole series of defense mechanisms dampen the pulse wave amplitude in order to ensure the continuous, even flow of blood to the intracerebral vessels. A similar relationship was also observed in recording the blood pressure on canulating the carotid artery against the blood stream, as compared with measurements in the same artery when the canula was directed cranially along the blood stream. Figure 170 illustrates this experimental setup in demonstrating the sharp dampening effect on the pulse wave in the vessels of the circle of Willis in comparison with its amplitude, as measured in the vessels at the base of the heart. We considered the dampening effect on the pulse wave in the circle of Willis to result first of all from the shock-absorbing effect of the arterial siphons formed by the carotid and vertebral arteries at their entry into the cranial cavity. The same purpose is served by the proximal convolutions of all larger arterial trunks to the brain which further dampen the pulse wave of cerebral blood flow. A second important arrangement for the transformation of the pulsatile blood flow into an even, continuous flow is the netlike distribution of the pial arteries. Because of these special anatomical arrangements, the amplitude range between systolic and diastolic blood pressure does not exceed 10mm in the vessels of the circle of Willis. On the other hand, this amplitude considerably increases if the hermetic sealing of the skull is impaired. In consideration with these data, we built a specially designed model of the cranial cavity. For this purpose a glass was filled with water, in which an air bubble was entrapped. The glass bulb was then connected to a mercury manometer of the Riva-Rocci type, (as shown in Figure 171,a). Any desired pressure could be obtained by inflating the balloon of the manometer. With this model it was possible to demonstrate that any pressure change of 20 mm in any direction resulted in the noticeable compression or expansion of the air bubble in the bulb (Figure 171,b). Pressure changes not exceeding 10 mm, however, gave hardly noticeable volume changes of the air bubble. In view of these results we enclosed in our "transparent skull" an air bubble which was noted to pulsate distinctly when one of the openings of the plexiglas roof was unscrewed. When the opening was sealed, the pulsations stopped immediately. It was necessary in these experiments to observe the air bubble with a capillaroscope. Thus, any pulsation of the brain or of any part of it would have been shown in changes in volume of the air bubble. It may thus be concluded that in the closed cranial cavity there are no recordable pressure changes during systole and diastole in the air bubble. It follows, therefore, that the already insignificant pulse wave of blood flowing in the intracerebral vessels is effectively opposed by the tonic state of the vessel walls. In such a case, however, it can no more be considered that blood flows in a continuous stream in the cerebral vessels, but rather that its progress is pulsative, with slight accelerations at each systolic contraction. This is an assumption consistent with the findings of those authors who noted a clearly pulsatile blood outflow from the sectioned jugular veins in animals whose skulls were hermetically sealed (Mosso). It should be pointed out, however, that in our investigations of the pial vessels through the capillaroscope in hermetically closed skulls we never observed this pulsatile progression of blood flow. On the contrary, in normal conditions as well as in prolonged blood depletion and after it, whenever it was possible to follow the progressions of erythrocytes it was seen that blood always flows in the vessels in an uninterrupted stream. Indeed tonic reactions of the blood vessels are triggered only when in raised blood pressure their walls are under stress exceeding a certain level. However, as long as the tonus of the vessel walls is higher than the pressure exerted on them, the blood stream in the vessels and capillaries accelerates without any concomitant changes in the vessel lumens. When blood pressure reaches a certain level at which the vessel wall can no more resist pressure forces exerted on it, the cerebral vessel dilates. Together with vasodilatation there is an increase in the cerebral blood volume. The volume of cerebrospinal fluid diminishes, and the subarachnoid space becomes narrower. Since in these circumstances there is also a manifold rise in cerebral venous blood pressure there is no possibility of compensatory cerebrospinal fluid transfer, and the question remains to be clarified as to where cerebrospinal fluid is reabsorbed. It may be assumed that cerebrospinal fluid flows out from the cranial cavity through the sheaths of the cranial and spinal nerves. However, our experiments in animals whose bony calvarium was replaced with a transparent plexiglas roof enabled us to refute categorically all claims of some authors that excess cerebrospinal fluid was reabsorbed by the dura mater. Indeed, if such were the case, then in all animals deprived of a large surface of their dura we should have observed under the transparent, plexiglas roof a noticeable accumulation of cerebrospinal fluid in the subarachnoid space. This accumulation of cerebrospinal fluid would also be expected to increase in time. In other words, we should have observed an external hydrocephalus and increased intracranial pressure in our animals. This, however, was not observed in any of the experimental animals. Intracranial pressure did not increase, and cerebrospinal fluid did not accumulate in measurable amounts. In view of this, we are led to the conclusion that the cerebral dural membrane does not participate in the resorption of cerebrospinal fluid.
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