March 5, 2018History of Medicine
Emanuel Swedenborg, born on 29 January 1688 and died 29 March 1772, was a Swedish scientist, philosopher, theologian, revelator, mystic and founder of Swedenborgianism. Swedenborg had a prolific career as an inventor and scientist. During the 1730s, Swedenborg undertook many studies of anatomy and physiology. He had the first known anticipation of the neuron concept. It was not until a century later that science recognized the full significance of the nerve cell. He also had prescient ideas about the cerebral cortex, the hierarchical organization of the nervous system, the localization of the cerebrospinal fluid, the functions of the pituitary gland, the perivascular spaces, the foramen of Magendie, the idea of somatotopic organization, and the association of frontal brain regions with the intellect. In some cases, his conclusions have been experimentally verified in modern times.
In the 1730s, Swedenborg became increasingly interested in spiritual matters and was determined to find a theory to explain how matter relates to spirit. Swedenborg's desire to understand the order and the purpose of creation first led him to investigate the structure of matter and the process of creation itself. In the Principia, he outlined his philosophical method, which incorporated experience, geometry (the means by which the inner order of the world can be known) and the power of reason. He also outlined his cosmology, which included the first presentation of his nebular hypothesis. There is evidence that Swedenborg may have preceded Kant by as much as 20 years in the development of that hypothesis. Although the first known observations of the CSF (cerebrospinal fluid) date back to Hippocrates (460-375 BCE) and later Galen (130-200 CE), its discovery is credited to Emanuel Swedenborg (1688-1772 CE), who, being a devoutly religious man, identified the CSF during his search for the seat of the soul. The 16 centuries of anatomists that came after Hippocrates and Galen may have missed identifying the CSF due to the time period's prevailing autopsy technique, which included severing the head and draining the blood before dissecting the brain. Although Swedenborg's work (in translation) was not published until 1887, due in part to his lack of medical credentials, he may have also made the first connection between the CSF and the lymphatic system. His description of the CSF was of a spirituous lymph.
In the peripheral organs, the lymphatic system performs important immune functions, and runs parallel to the blood circulatory system to provide a secondary circulation that transports excess interstitial fluid, proteins and metabolic waste products from the systemic tissues back into the blood. The efficient removal of soluble proteins from the interstitial fluid is critical to the regulation of both colloidal osmotic pressure and homeostatic regulation of the body's fluid volume. The importance of lymphatic flow is especially evident when the lymphatic system becomes obstructed. In lymphatic associated diseases such as elephantiasis (where parasites occupying the lymphatic vessels block the flow of lymph), the impact of such an obstruction can be dramatic. The resulting chronic edema is due to the breakdown of lymphatic clearance and the accumulation of interstitial solutes. In 2015, about 300 years after Emanuel Swedenborg, the presence of a meningeal lymphatic system was first identified. For over a century the prevailing hypothesis was that the flow of cerebrospinal fluid (CSF), which surrounds but does not come in direct contact with the parenchyma of the CNS, could replace peripheral lymphatic functions and play an important role in the clearance of extracellular solutes.
The majority of the CSF is formed in the choroid plexus and flows through the brain along a distinct pathway: moving through the cerebral ventricular system, into the subarachnoid space surrounding the brain, then draining into the systemic blood column via arachnoid granulations of the dural sinuses or to peripheral lymphatics along cranial nerve sheathes. Many researchers have suggested that the CSF compartment constitutes a sink for interstitial solute and fluid clearance from the brain parenchyma. However, the distances between the interstitial fluid and the CSF in the ventricles and subarachnoid space are too great for the efficient removal of interstitial macromolecules and wastes by simple diffusion alone. Helen Cserr at Brown University calculated that mean diffusion times for large molecules such as albumin would exceed 100 hrs to traverse 1 cm of brain tissue, a rate that is not compatible with the intense metabolic demands of brain tissue. A clearance system based on simple diffusion would additionally lack the sensitivity to respond rapidly to deviations from homeostatic conditions. Key determinants of diffusion through the brain interstitial spaces are the dimensions and composition of the extracellular compartment. In a series of elegantly designed experiments in the 1980s and 1990s, C. Nicholson and colleagues from New York University explored the microenvironment of the extracellular space using ion-selective micropipettes and ionophoretic point sources. Using these techniques Nicholson showed that solute and water movement through the brain parenchyma slows as the extracellular volume fraction decreases and becomes more tortuous.
As an alternative explanation to diffusion, Cserr and colleagues proposed that convective bulk flow of interstitial fluid from the brain parenchyma to the CSF was responsible for efficient waste clearance. Experiments conducted at the University of Maryland in the 1980s by Patricia Grady and colleagues postulated the existence of solute exchange between the interstitial fluid of the brain parenchyma and the CSF via paravascular spaces. In 1985, Grady and colleagues suggested that cerebrospinal fluid and interstitial fluid exchange along specific anatomical pathways within the brain, with CSF moving into the brain along the outside of blood vessels. Grady's group suggested that these ?paravascular channels' were functionally analogous to peripheral lymph vessels, facilitating the clearance of interstitial wastes from the brain. Other labs at the time, however, did not observe such widespread paravascular CSF-ISF exchange. The continuity between the brain interstitial fluid and the CSF was confirmed by H. Cserr and colleagues from Brown University and Kings College London. The same group postulated that interstitial solutes in the brain parenchyma exchange with CSF via a bulk flow mechanism, rather than diffusion. However other work from this same lab indicated that the exchange of CSF with interstitial fluid was inconsistent and minor, contradicting the findings of Grady and colleagues.