Table of Contents

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Table of Contents

Information Signaling and Processing in the Vascular System

Table of Contents

Abstract 

This report explores the notions of design and function of the vascular system as products of evolutionary processes in the framework of information storage and processing. The vascular system serves as a transportation system, delivering oxygen and sugars to other organs. The brain is the main site of information processing in animals and requires energy and glucose to function. Thus, the vascular system will be explored as a mechanism to deliver and remove biochemicals to and from the brain. Specific architectures and densities of the vascular system around the brain will be discussed. Natural redundancy will be considered as a design factor to ensure vascular resiliency. The blood-brain barrier will be detailed as a mechanism to precisely regulate the flow of ions and biomolecules between blood and the brain in order to maintain homeostasis in the brain parenchyma. Plant vasculature will be presented as a heterogeneous design whose roles in computation are achieved through bi-directional signaling, refined coordination between pathways, and through signal molecules and structural constituents of the tissue. A comparative analysis to the vasculature of animals will be presented in the context of evolution.

Vasculature Surrounding the Brain

Connecting Vascular Function with Information Processing

From the perspective of information processing, the vascular system is responsible for delivering biochemicals to the brain and disposing of waste produced from sugar metabolization (Özugur et al., 2020). The brain consumes disproportionately high quantities of oxygen and glucose compared to its mass, requiring a quarter of the body’s glucose and a fifth of its oxygen (Schmid et al., 2019). This is understandable, as the brain is responsible for countless operations including voluntary movement, language, sensory information processing, and thinking (Duvernoy et al., 1981). However, the brain lacks the infrastructure to store energy, and thus requires a constant external supply from the vasculature; it transports oxygen and glucose consistently and efficiently to maintain an organism’s ability to process information (Smith et al., 2019). As the brain metabolizes glucose to create usable energy, carbon dioxide is produced as a by-product. Fortunately, carbon dioxide is promptly removed from the brain by veins. Because of the brain’s reliance on glucose, oxygen, and carbon dioxide transfer, the vascular system plays a pivotal role in information processing and controlling the behavior of an organism.

Capillary Properties in the Cerebral Cortex

The cerebral cortex plays a significant role in information processing and needs high quantities of glucose and oxygen to function. As a result, it is interesting to consider its intricate network of blood vessels which allow it to function. Operation of the cortical vascular system is achieved through strictly organized and regulated architecture, which has evolved to ensure efficient and fast transportation of glucose and oxygen (Duvernoy et al., 1981). Oxygen and glucose diffusion to brain tissues occurs at the capillaries, and thus their architecture is highly important to information processing. Consequently, capillaries are the most abundant type of blood vessel in the cortical vasculature (Blinder et al., 2013). Their size varies greatly depending on the organism, but in humans their diameter has been reported as 6.23 ± 1.3μm (Cassot et al., 2009).

Capillary networks appear quite complex as seen in Fig. 1a. However, they are strictly organized into homogenous, redundant, and meshed units. Networks are composed of tessellated elementary cubic lattice units as shown in Fig. 1b – d. The mesh width is dependent on the diffusion constant of a specific brain tissue, as to ensure no oxygen-needing tissue is further from the capillary than the diffusion length (Moan, 1990).

Fig. 1 (a) A section of a mouse’s vasculature in the cerebral cortex. Three 240 μm3 sections are outlined in purple. (b) A smaller cross section. (c)The vessels in the same cross section straightened. (d)The capillaries in the cerebral network are composed of elementary components in simple, cubic lattices. The cubic lattice has a characteristic length, Lc. [Adapted from Smith et al., 2019]

Differing metabolic demands motivated different evolutionary design of the vascular system among brain regions (Cavaglia et al., 2001). Regions of the brain that require more energy have higher capillary mesh densities. Cavaglia et al. (2001) studied the difference in capillary density in grey and white matter in the brain, concluding that the density is much higher in grey matter. Density differences are explained by the primary cell types and their metabolic demands. Grey matter is composed of synapses and principal cells, such as glial cells and neuropil, which require high quantities of energy to function. On the contrary, white matter is mainly axons, which do not demand as much energy. Numerous regions of the brain stained and imaged using UV fluorescence in Fig. 2a – d to provide evidence of the differing densities. The region-specific densities of the capillary networks illustrate how the architecture of the vascular system was naturally designed to ensure optimal function.

Fig. 2 Imaging of a rat brain, showing that different sections of the brain have differing capillary densities, depending on their metabolic demands. [Adapted from Cavaglia et al., 2001] (a) The frontal cortex. The capillary network is extremely dense. (b) A section of the brain transitioning between grey and white matter. The intense difference in capillary density between regions is evident. (c) The vascular system in the substantia nigra pars compacta and reticulata (SNc and SNr, respectively). (d) Imaging of the supramammillari nuclei (SMn) and medial mamillari (Mmn).

Natural Redundancy

The vasculature in the brain has evolved to be redundant, protecting organisms from brain death if the primary system malfunctions. As previously mentioned, the meshed capillary networks are redundant to ensure persistent blood flow. Further, cortical arteries have redundant connections branching between them, ensuring a localized blockage does not stop the system from delivering blood to the brain (Gross, 2006). Imaging of a section of a rat’s brain is shown in Fig. 3, which illustrates its interconnected arteriole network (Gross, 2006). Redundant architecture in capillaries and arterioles ensures the brain vasculature can quickly re-establish blood flow if problems arise.     

Fig. 3 Imaging of the redundant branching of arterioles in the rat parietal cortex. [Adapted from Gross, 2006] The connecting branches ensure the arterioles can still transport blood if localized blockages form.

More notably, there is an entire network of arteries at the base of the brain, called the circle of Willis, which creates a redundant pathway for blood to be distributed to the brain (Kalsoum et al., 2014). It was named after Sir Thomas Willis, a man whose right carotid artery, which is normally the primary vessel transporting blood to the brain, was completely blocked (Gross, 2006). Surprisingly, the blocked carotid artery was not responsible for his death. The researchers concluded that there must be a redundant network providing blood to the brain, leading to the discovery of the circle of Willis. It has since been determined that the circle of Willis is present in many mammals and birds, including dogs, rabbits, goat, sheep, and monkeys (Kapoor et al., 2003).

The circle of Willis loops around the brainstem and connects with the anterior, middle, and posterior cerebral arteries, as seen in Fig. 4 as ACA, MCA, and PCA, respectively (Kalsoum et al., 2014). They are connected via posterior communicating arteries (PComA). The circle is designed such that damaged to it is insignificant; blood flows collaterally in either direction around the circle, and thus its function is maintained.

Fig. 4 The structure of the circle of Willis is designed to be resistant to damages, ensuring blood flow to the brain is persistent. [Adapted from Kalsoum et al., 2014] Some key features are its symmetry, closed looping nature, and thin posterior communicating arteries.

Since the brain controls information processing and the ability of an organism to survive, its vasculature is designed to protect against problems that commonly arise, such as localized blockages. The circle of Willis is an evolutionary phenomenon tasked with ensuring the brain receives glucose and oxygen in the case that the primary vasculature fails. Its presence demonstrates the development of architecture to ensure the function of the vascular system proceeds despite complications. Vascular resiliency is of particular importance for vessels around the brain as the brain requires constant oxygen and glucose to process information and keep an organism alive.

The Blood Brain Barrier

As established in previous sections of this report, proper function of blood vessels and capillaries is critical to ensure adequate delivery of oxygen and nutrients to the brain. The brain, however, has specific requirements in terms of the substances it can allow in its extracellular fluid in order to prevent deregulation of neurological functions (Keaney and Campbell, 2015). For this, a unique and particular structure exists within the blood vessels of the central nervous system to allow a better regulation of substance, and cell flow between the brain and the blood. This structure is called the hematoencephalic barrier, or blood-brain barrier (Daneman and Prat, 2015).

The blood-brain barrier (BBB) possesses unique properties, it tightly controls the influx and efflux of substances in the brain interstitial fluid. The barrier not only prevents certain toxins, drugs, and biomolecules from entering the brain while ensuring the delivery of nutrients and oxygen, but also participates in the removal of toxins produced in the interstitial fluid (Obermeier et al., 2016).  This allows for the maintenance of the ideal conditions for neurological functions aforementioned, essential for the communication of information throughout the body.

Endothelial Cells and Transport Mechanisms

The specific type of endothelial cells that compose the blood vessels in the BBB are responsible for most of the shielding properties of it, although the BBB is a structure that also associates other types of cells (Keaney and Campbell, 2015). Endothelial cells of the BBB have a continuous intercellular tight junction, unlike elsewhere in the body. So, the space between cells is greatly reduced. This greatly limits the paracellular diffusion of substances, solutes, and ions, creating a polarized barrier between the lumen and the abluminal compartment. These endothelial cells also have no fenestrae, or pore-like structures, in their cell membrane, which further limits the permeability of the capillary as shown in Fig. 5 (Daneman and Prat, 2015).

Fig. 5 Two of the main types of capillaries. [Adapted from Kanasty et al., 2012] The blood-brain barrier is composed of continuous, non-fenestrated capillaries, with tight junctions. This structure limits the permeability of the capillary.

Finally, endothelial cells in the central nervous system capillaries are subject to extremely low rates of transcellular transport, or transcytosis. So, the transport of substances through vesicles is greatly restricted, although it can happen if a receptor specific to a compound is present within the lumen as displayed in Fig. 6d (Daneman and Prat, 2015; Obermeier et al., 2016).

Because of this, other regulated transport mechanisms are essential to permit the exchange of compounds through the endothelium. These transport mechanisms are aided by the polarized compartments created by the low rates of paracellular and transcellular transport, and control almost all exchanges. Two main types of transport channels exist in the endothelial cells composing the BBB: efflux transporters and nutrient transporters as shown in Fig. 6 (Daneman and Prat, 2015). Efflux pumps are mostly located in the luminal surface of endothelial cells, and transport substrates from the brain to the blood against the concentration gradient (Fig. 6c). They also prevent small lipophilic molecules that could easily diffuse out of the brain interstitial fluid from escaping it. This type of transporter is ATP-dependent, which is why cerebral endothelial cells have a greater number of mitochondria relative to other endothelial cells (Daneman and Prat, 2015; Obermeier et al., 2016). Nutrient transporters, which are receptor-mediated, ensure the delivery of substances in the opposite way, from the blood to the brain, and goes with the concentration gradient (Fig. 6d). A wide range of these transporters exists, to allow only specific compounds to enter the central nervous system, including glucose and amino acids (Abbott et al., 2006; Daneman and Prat, 2015; Obermeier et al., 2016).

Fig. 6 The principal pathways for the transportation of molecules through the BBB. [Adapted from Abbott et al., 2006] (a) Normally, the tight junctions severely restrict penetration of water-soluble compounds, including polar drugs. (b) The restricted ability for passive diffusion is displayed. (c) The receptor-mediated nutrient transport mechanism is shown, along with the be ATP-dependent efflux pathway. (d) A receptor-specific transcytosis pathway is illustrated. (e) Transcytosis is shown, although this pathway has an extremely low rate.

These channels thus allow for a more controlled diffusion of specific species of substrates instead of a passive, uncontrolled, diffusion, that may impede on cerebral function.

Other Cells of the Blood-Brain Barrier

The other types of cells, and structures that participate in maintaining and regulating homeostasis in the brain parenchyma are pericytes and astrocytes, seen in Fig. 7. Pericytes cover over sixty percent of the abluminal surface of endothelial cells and are named as such as they wrap around the vessel (Vazquez-Villaseñor et al., 2020; Obermeier et al., 2016) (Fig. 7b – d). These cells are responsible for controlling the diameter of the capillary as they contain contractile proteins, like actin, and adjust blood flow in accordance with the level of neural activity (Daneman and Prat, 2015). They also participate in the reduction of transcytosis, or vesicle-mediated transport through endothelial cells, and increase efflux transport system activity (Obermeier et al., 2016).

Fig. 7 The components of the blood-brain barrier are illustrated. [Adapted from Daneman and Prat, 2015] (a) Vascular cast of the spinal cord, to show the high density of the microvasculature in the central nervous system. (b) Electron micrograph (EM) of a cross section of a CNS vessel depicting a relationship among endothelial cells (ECs), pericytes (PCs), and astrocytes.(c) Magnified EM of ECs depicting a relationship among ECs (with tight junctions [TJ]), PCs, basement membranes (BMs), and astrocyte endfeet (AE). (d) A schematic representation of the cell types within the neurovascular unit. (e) An immunofluorescence micrograph, displaying pericytes (orange) and endothelial cells (green). (f) Micrograph illustrating the relationship between astrocytes (red) and capillaries (unstained); as astrocytes enclose the capillaries entirely, their outline can be visualized by observing the end-feed of astrocytes.

Astrocytes are the most abundant types of cells in the brain and their end-feet cover the entirety of the brain microvasculature (Vazquez-Villaseñor et al., 2020) (Fig. 7f). These cells provide a cellular link between the cells of blood vessels and neurons, they are thus responsible for relaying the signals that influence and control blood flow in response to neural activity (Daneman and Prat, 2015). Besides this, one of the major roles of astrocytes is the protection of neurons by maintaining stable concentrations of neurotransmitters, ions and water in the brain interstitial fluid. They also contribute to the maintenance of the integrity and structure of the BBB, as they increase the tightness of the barrier (Keaney and Campbell, 2015). 

It is critical to note, however, that not all parts of the brain contain a microvasculature that forms a blood-brain barrier. Some brain functions require a less restricted access to the bloodstream and thus a BBB would be detrimental to these functions. This includes the pineal gland and the pituitary gland, whose vessel has a much higher passive permeability, thus rendering diffusion a less restricted process. These regions of the brain participate in hormonal control, this function would be hindered in the presence of a barrier impeding on passive diffusion (Daneman and Prat, 2015).

Plant Vasculature

Heterogenous Design and Comparative Analysis to Animals

In addition to its roles in resource translocation and the provision of mechanical support, the vascular system of plants serves as a long-distance communication pathway that enables their responses to biotic and abiotic stressors in their environment. The vascular system can be analyzed as a heterogeneous design in order to introduce a framework for maximizing the suitability of a tissue’s architecture to its role in information processing (Duran-Nebreda and Bassel, 2019). The design is considered heterogeneous because it shortens the network involved in information transfer, creating a centralized pathway for its flow. This presents a trade-off; the rate of transfer is increased at the expense of the system’s capacity to respond to “random noise” defined as the arbitrary or intended failure of its constituents (Duran-Nebreda and Bassel, 2019). As a result, the cellular arrangement of plants displays a distributed design, characterized by isotropy and lattice-like structures that conversely exhibit slower speeds of transfer but a higher robustness to noise (Duran-Nebreda and Bassel, 2019). In conjunction with redundancies in architecture, components of distributed design at the cellular level ensure that the long-range information processing undertaken by the vascular system does not compromise the organism’s overall resilience to the random failure of parts.

To some degree, the linking of translocation pathways through bi-directional signaling replicates the connections established by the animal circulatory and nervous systems throughout the body (Notaguchi and Okamoto, 2015). In the absence of the intricate cellular wirings and ion channel set that animals possess to convey long-distance electrical signals, plants have adopted an architecture to adapt to the electrical communication necessary for survival in their environments (Canales et al., 2018). Stimuli detected in various locations throughout the plant relay information to the xylem and phloem, followed by the signal’s integration and relay to effector tissue (Canales et al., 2018). An interconnected cellular structure equips it with the plasticity necessary for computation without a central integrator that animals possess in the form of a brain (Canales et al., 2018).  Levels of vascular organization that will be further analyzed in the context of signal transmission are presented in Fig. 8.

Fig. 8 Levels of vascular organization. [Adapted from Berleth et al., 2000] (a) Cell alignment in a pro-vascular strand of a leaf primordium. (b) Variable network of vascular strands in an Arabidopsis leaf. (c) Internal array of vascular bundles in an Arabidopsis stem.

Classes of Signals

The signals plants employ to adapt to imposed stresses can be categorized in three groups according to their transmission rates and distances as well as the stimuli that initiate them: hydraulic, chemical, and electrical (Huber and Bauerle, 2016). Hydraulic signal transmission uses water as a medium for exchange to govern the rates of cell expansion, which vary according to the turgor pressure changes that begin in xylem vessel conduits and transmit to adjacent cells as a result of low axial pressure (Huber and Bauerle, 2016). Due to the slow rate of transport of the xylem, chemical signals are primarily involved instead in short-distance, cell-to-cell communication (Hlavácková and Naus, 2007). The electrical signals in plants can be further divided into three classes: action potentials (APs), slow wave potentials (SWPs), and wound potentials (WPs). The transmission of APs is primarily along the phloem and is initiated in response to innocuous stimuli, including acid rain and responses to the cold (Huber and Bauerle, 2016). A rapid depolarization of the membrane potential is proceeded by a rapid repolarization phase, and average rates of propagation vary from 1 cm/s to 2 cm/s with uniform amplitudes and velocities (Huber and Bauerle, 2016).

SWPs travel along the xylem following mechanical injury or burns with a preliminary rapid depolarization and subsequent repolarization phase (Huber and Bauerle, 2016). In contrast to APs, the amplitude and rate of transmission vary with the signal’s distance from the location of initiation and are elicited in response to hydraulic pressure changes, rather than being self-perpetuating (Huber and Bauerle, 2016). The dependence on the hydraulic signal reduces the intensity of the signal as water is transported in a radial direction from the xylem into epidermal cells (Huber and Bauerle, 2016). In comparison to APs, the signals’ varying intensities, pressure, and shape enable the processing of more information about the degree of the injury and the position of its source (Huber and Bauerle, 2016). WPs, in response to wounding, proceed turgor pressure changes and exhibit similarities to SWPs in their ionic processes but are transmitted over shorter distances of 1.0 – 40.0 mm from the wound site (Huber and Bauerle, 2016).

Electrical signals represent an area of research for carnivorous plants, since they serve as adaptations that they require to procure their prey, and by extension, nitrogen supply. To illustrate, Dionaea, commonly known as the Venus flytrap, relies on electrical signals propagated through leaf traps for the subsequent release of elastic energy involved in its closing (Fromm et al., 2013). They also serve as evolutionary adaptations for Mimosa, where movement generated in the leaflets reduces their appeal to predators, and heat-induced signals result in systemic decreases in net carbon dioxide intake (Fromm et al., 2013).

Coordinated Systems

Engineered systems rely on the coordinated storage, transportation, and processing of information for computation (Duran-Nebreda and Bassel, 2019). As a biological system, the vascular system of plants can be viewed under the same lens. An experiment conducted on the exposure of tobacco plants to local burning concluded that electrical, hydraulic, and chemical signals act in conjunction, rather than in isolation, to address wound response. Following the burn, a hydraulic surge conveyed in basipetal and acropetal directions through the xylem exported chemicals released at the local burn site (Hlavácková and Naus, 2007). As a result, ion fluxes in surrounding cells alter, and electrical activity is generated (Hlavácková and Naus, 2007).

 “Root-to-shoot-to-root” represents a union of the xylem and phloem pathways in conveying signals from one portion of the roots to another (Notaguchi and Okamoto, 2015). Unidirectional signal flow is achieved by the upward flow of xylem sap from the roots following transpiration and the transport of phloem sap from mature leaves to sink organs, representing isolated xylem and phloem pathways (Notaguchi and Okamoto, 2015). Conversely, bi-directional signaling, as illustrated in Fig. 9, through the integrated communication between vascular tissues, serves as a mechanism for refined signaling (Notaguchi and Okamoto, 2015). In response to soil conditions, signaling molecules released in the root system move along the xylem, disperse to mature leaves, translocate to the phloem, and are detected by receptors on the vascular tissue where they are transformed to a secondary signal (Notaguchi and Okamoto, 2015). Following this, the secondary messengers are conveyed along phloem sap to another portion of the root (Notaguchi and Okamoto, 2015).

Fig. 9 Model of long-distance signal transmission in the xylem and phloem of plants. [Adapted from Notaguchi and Okamoto, 2015] (a) Molecules involved in signal transmission in the xylem (blue) and phloem (red). (b) and (c) Convergence of vascular pathways in communication, where signals are transmitted from the xylem to the phloem in vein (b) and stem (c). Abbreviations: Xy: xylem; Ph: phloem; CC: companion cell; SE: sieve element; PD: plasmodesmata.

Hormone Signaling

Hormonal Signaling and Vascular Structural Constituents

Mobile molecules such as hormones and structural constituents of the xylem and phloem are involved in both bi-directional and unidirectional signaling. The sieve tube elements and companion cells of the phloem, displayed in Fig. 10, provide pathways of low resistance for conducting and transmitting signals along the plasma membrane (Fromm et al., 2013). This can be attributed to the nature of their symplastic connections and the presence of a saline luminal fluid (Fromm et al., 2013). The continual permeable nature of sieve elements contributes to a high capacitance conduit that permits steady signal transmission (Canales et al., 2017). The apoplastic space and plasmodesmata enable the transmission of soluble signals and regulates signals involved in calcium ion response (Canales et al., 2017).  As well, mobile phytohormones, proteins, and transcripts serve as the bases for systemic signaling, where they are transported as signal agents (Notaguchi and Okamoto, 2015). These physical properties provide a body of evidence for the correlation between electrical signals and calcium ion influx in the phloem of Populus trichocarpa, known as Black cottonwood, where the latter is a pre-requisite for the generation of the former, along with the resulting chemical responses (Fromm et al., 2013). Long-range signaling factors present in the xylem include phytohormones involved in root-to-shoot coordination, mobile proteins, and secreted oligopeptides that mediate communication between organs (Notaguchi and Okamoto, 2015).

Fig. 10 Schematic of sieve tube elements and their constituents. [Adapted from Angyalossy et al., 2020] (5) Sieve tubes and local companion cells at 50μm. (6) Elements with inclined sieve plates in lateral and tangential sections at 50μm. (7) Collapsed sieve-tube elements, alternating with non-collapsed parenchyma cells 100μm.

Comparing Plant and Animal Signaling

As previously discussed, plants rely mostly on hormonal signaling and the transmission of electrical impulses from cell to cell to relay information across their body whereas animals benefit from a combination of both hormonal and neural signaling. The reason for this difference in signaling pathways is very simple: plants do not have a brain and therefore cannot transmit signals through a nervous system. Because of their sedentary lifestyle, plants never required a brain to function properly since they are not subject to as much stimuli as animals are. Indeed, the “brain is very expensive organ, and there’s absolutely no advantage to the plant to have a highly developed nervous system” (Taiz et al., 2019). Thus, even though plants cannot think or react to stimulus as fast as animals can, they are still very well adapted to their environment to ensure no energy is expended unnecessarily. On the other hand, the development of a brain was crucial for animals since their active lifestyle demanded a fast signal transmission that hormonal signaling could not accomplish.

Interestingly enough, the fact that both plants and animals employ hormonal signaling shows that it is a very ancient signaling pathway that was used by organisms before evolution separated plants and animals about 1.5 billion years ago. The nervous system is thought to have evolved much later in animals, about 500 million years ago, with the “initiation of predator–prey interactions for the purpose of obtaining food” (Taiz et al., 2019). Now, how do animals manage the use of two distinct signaling pathways, and why would they need both? These questions are addressed in the following three sections.

The Combination of Neural and Hormonal Signaling Pathways in Animals

How do animals respond to stress? Let us take the example of one of the many squirrels living on the McGill campus to demonstrate how they respond to stimuli. In the context where a person passes near the squirrel and startles it, first, the senses will send electrical signals to the brain, which will relay those signals to the muscles, allowing the squirrel to move away from the danger. At the same time, a nerve impulse is sent to the adrenal medulla (Fig. 11) where the production of epinephrine, also known as adrenaline, is triggered (“Adrenal Glands” | Johns Hopkins Medicine, n.d.). Those hormones are released in the arteries, and they provoke physiological alterations that will enable to animal to better react to this situation of danger (Ulrich-Lai and Herman, 2009). Adrenaline increases the heart rate, augments blood pressure and dilates the bronchioles (Fig. 11), all of which have one objective: furnish more oxygen more rapidly to the organs and muscles so that the animal can flee the danger. All these changes are known as the “flight or fight” response, a phenomenon described in the early 1900s as the reaction of an animal to perceived danger (Cannon, 1929). The autonomous nervous system (ANS) is responsible for this first reaction to a stressor, and it happens so quickly that the animal does not even have the time to think about it; it is a reflex (“Understanding the stress response” | Harvard Health Publishing | Harvard Medical School, 2020).

Fig. 11 The release of catecholamines in the blood vessels after a stress, and their effects on the various organs of the body. [Adapted from “What are Catecholamines (Total)” | Health Matters, 2018] Catecholamines are composed of three hormones, one of which is adrenaline.

Shortly after the “flight or fight” response, the hormonal signaling pathway working together with the circulatory system comes into play with the activation of the hypothalamo-pituitary-adrenocortical (HPA axis), a cascade of releasing factors that eventually leads to the production of cortisol (Fig. 12). Indeed, as part of the stress-response, the hypothalamus will release the corticotropin-releasing factor (CRF) in the blood vessels, which make its way to the pituitary gland where ACTH is released. Then, ACTH reaches the adrenal cortex where glucocorticoids are secreted (Smith and Vale, 2006). Glucocorticoid, also known as cortisol, is a hormone essential to the stress-response of an animal since it keeps the body on high alert, but also acts as an anti-inflammatory (Hannibal and Bishop, 2014). Studies have shown that the cortisol levels start rising about fifteen minutes after the initial stress and they remain high for a few hours (Hannibal and Bishop, 2014). Thus, if the squirrel bruises its leg trying to run away from danger, it might not feel anything until a few hours after the danger has passed. This is a phenomenon that people can relate to, especially for those who perform in a contact sport where the adrenaline and cortisol levels are high during the practice of the sport, and so bruises are felt only a few hours after the end of the activity.

Fig. 12 Functioning of the HPA axis in animals, starting at the hypothalamus and ending with the production of cortisol in the adrenal cortex. [Adapted from Alschuler, 2016]

The adrenal cortex, which is responsible for the release of cortisol, is a section of the adrenal gland located just above the kidneys. A cross-section of the adrenal gland shows that it is divided in two parts (Fig. 13): the exterior is the adrenal cortex, and the interior is the adrenal medulla which we saw earlier is responsible for the release of adrenaline in the blood vessels. Adrenaline and cortisol are crucial to the stress-response of animals, and the circulatory system has the important role of bringing those hormones where they need to be.

Fig. 13 Cross-section of the adrenal gland where the adrenal cortex is the exterior labeled C, and the adrenal medulla is the interior labelled M. [Adapted from Hough, 2012] The white circular region in the middle in a blood vessel.

Effect of Food on Stress-Response in Animals

After consuming a large meal, feelings of lethargy are common. This is caused by many reasons, one of which is the affluence of melatonin in the blood vessels, a hormone that relaxes the body (Meng et al., 2017). However, what truly deserves our attention is that, after the consumption of food, various nutrients, sugars and hormones contained in food circulate in the bloodstream at the same time. Thus, suppose an animal is enjoying a meal and suddenly finds itself in a position of danger that requires a rapid reaction. It is very possible that the stress-response will not be adequate because there is a “traffic jam” in the blood vessels. Of course, the nervous system is not affected since the electric signals do not go through the blood vessels, so the animal will most likely be able to move away from danger. However, the adrenaline that normally rushes in the blood vessels and causes several physiologic changes in the body such as increased heart rate and increased oxygen intake might be delayed since it needs to travel in the nutrient-saturated blood vessels (Ulrich-Lai and Herman, 2009). The release of cortisol and other hormones that are normally released as part of the stress-response would probably be delayed as well. Therefore, the immediate reaction of the animal might not be impacted by the intake of food, but the hormones that help the animal escape from a chase will likely be delayed which could lead to the animal being caught by its prey since the body would not be adapted for the situation. This is a component of the stress-response in animals that needs much more research since studies on this subject are scarce.

Hormonal Signaling Versus Neural Signaling: Is One Better than the Other?

Each signaling pathway has evolved to serve distinct functions, and they both accomplish their functions in refined ways, so they cannot be compared as such. Plants have a sedentary lifestyle, so a slower signaling pathway such as hormonal signaling satisfies their needs and does not require too much energy whereas animals have an active lifestyle, so they require a combination of hormonal signaling and a brain that can allow fast reactions even if it takes a lot of energy.

However, one can wonder for the sake of parsimony why animals use hormonal signaling since they already have a faster way of transmitting information in neural signaling. A hypothesis could be that neural signaling is very sensitive to every stimulus perceived by the senses, and thus makes for an unstable way of signaling. On the other hand, hormonal signaling is only used for some specific signals, which makes it a much more stable and reliable signal pathway. Another reason for this combination of signaling pathways might not please engineers, but the fact is that the combination of both systems just works well and there is no need to change this. In his book “Quirks of Human Anatomy”, Lewis I. Held, Jr demonstrates how there are some components of the human body that cannot be explained logically, they simply work well. Indeed, he explains that “human embryos make many structures we do not need, and we destroy others after we’ve gone to the trouble of making them” (Held, 2009).

Conclusion

The operation of the brain, and thus information processing of an organism, requires extraordinary quantities of oxygen and glucose. The vascular system’s function is to transport these biomolecules to the brain and remove waste. Capillaries are of particular interest as they are the location of oxygen transfer from the vascular system to brain tissues. Capillary networks are formed by elementary units meshed with heterogenous densities to meet the metabolic demands of particular regions in the brain. Once again, this illustrates how the form of the vascular system follows its function. Redundancy is an important evolutionary development that ensures resiliency of the vasculature. Particularly, the circle of Willis is a redundant network that ensures blood flow if the primary system fails. The architecture of the vascular system around and in the brain ensures persistent and high supplies of blood flow, ensuring the transport of oxygen, glucose, and carbon dioxide. Ultimately, transportation of blood by the vasculature allows the brain to process information.

The body’s vasculature has different properties that depend on the requirements of the organ or the tissue they vascularize. The precise homeostasis that is required in the brain interstitial fluid, to preserve neurological function, is maintained by the blood-brain barrier. It is yet another illustration of the intertwined relationship that form and function have in nature. To ensure the stability of this environment, endothelial cells in the central nervous system have tight intercellular junctions that prevent passive diffusion and possess specific transport mechanisms to allow for the delivery of required nutrients into the brain parenchyma. Pericytes and astrocytes participate in the maintenance of the structural integrity of the blood brain barrier and enhance the efficiency of the transport mechanisms. Unfortunately, due to its effectiveness, the blood-brain barrier poses a problem for drug delivery within the brain. Compounds are not able to effectively enter the brain interstitial fluid to execute their function. For this, workarounds — such as creating compounds that can bypass nutrients transporters, or that induce vesicle-mediated transportation — still need to be researched.

The role of the vasculature system in plants extends beyond resource translocation and mechanical support to serve as a long-distance signal transmission pathway defined by hormonal signaling and bi-directional flow. Plants rely on three categories of signals that vary according to transmission rate and distance, and designs that display both heterogeneity and distribution ensure that the vasculature can transfer information at an optimal rate without compromising the resilience to the random failure of parts. Plants developed this signaling pathway since they do not possess a brain whereas animals developed a combination of hormonal and neural signaling to support their active lifestyle. The evidence of hormonal signaling in both plants and animals suggests that it is a very ancient signaling pathway that existed before plants and animals parted ways. Applying engineering perspectives allows for a profound understanding of the role of the vascular system on information processing, computation, and signaling perspectives. Analyzing the vascular structures related to transportation to the brain, signaling, and information processing highlights the important engineering design factor of natural redundancy. Most notably, the architecture of the vascular system is designed such that it meets the respective function as analyzed in both plants and animals.

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