How Do Nerve Cells Send Signals? — A Burning Fuse, a Gap Crossed by Ferry

Until We Call Its Name

Someone is waving from across the street. The eyes see that face, recognize that it is an old friend, and the mouth calls out the name. It is a shorter time than taking a single breath. In that span, countless signals went back and forth between the eyes, inside the head, and to the mouth.

The news says many things about these signals. There are claims that a certain substance creates joy, or that if a certain substance is lacking, the mind sinks. To read such words properly, one must first know how signals are generated and how they are carried.

This article follows the path that a single signal takes. It looks in turn at what kind of cells the brain and nerves are made of, how a signal races inside a single cell, how it crosses the gap between cells, and how that connection changes depending on use.

860 billion, and just as many neighbors

For half a century, it was widely accepted as established fact that the human brain has 100 billion nerve cells, and that the cells beside them outnumber them tenfold (PMID 27187682). Nerve cells are the basic cells of the brain and nervous system that receive electrical signals and pass them on to the next cell. They are also called neurons, following their English name.

In a study that counted an adult man's brain using a new counting method, there were an average of about 86 billion nerve cells, and non-nerve cells were similarly numbered at about 85 billion (PMID 19226510). When counted again using this method, the surrounding cells were not more numerous than the nerve cells, and old microscope data had also pointed to roughly a 1-to-1 ratio from the beginning (PMID 27187682). The saying that "90% of brain cells are surrounding cells" was also settled as incorrect (PMID 24807023). Nearly the same number of nerve cells and other cells live together in the brain.

Glial cells are non-nerve cells of the brain and nervous system that sit beside nerve cells, protect the environment in which nerve cells work, and even meddle in their signals. The "glia" comes from glue, a name given because they were thought to fill the spaces between nerve cells like glue (PMID 26084688). Looking at the whole brain, glial cells are similar in number to nerve cells, but their proportion varies greatly from place to place in the brain (PMID 26084688). Although glial cells were long regarded as mere bystanders that only provided support from the sidelines, they are now understood to lend a hand in almost every process of how the brain is built and works (PMID 30309945). The work of glial cells is broadly bundled into two categories: maintaining the balance of things like water, ions, and fuel, and defending the nervous system from intruders like microbes (PMID 31583582).

There are several branches of glial cells. Astrocytes are glial cells that branch out in a star shape to surround nerve cells and blood vessels. Astrocytes are the most numerous glial cells in the brain (PMID 39358030). Microglia are immune cells that stay within the brain and watch for damage and invasion. Microglia also meddle in pruning away parts of neural connections, and depending on the situation, they either protect or harm nerve cells (PMID 42243476). The third branch makes a sheath that speeds up signals, which we will meet again later in this article.

The brain is an organ where nerve cells and, when looking at the brain as a whole, a similar number of glial cells work together.

Inside a Single Cell, It Runs on Electricity

Neurons are shaped like a round body with two kinds of branches extending outward. Dendrites are short branches that spread out in multiple ways from the neuron's body, designed to receive signals sent by other cells. An axon is a single, long branch that stretches out from the neuron's body, designed to send signals onward to the next cell. This direction—dendrites receiving and axons sending—is the basic sequence of neural signals.

Signals from many different places arrive at a single neuron all at once. Neurons gather these signals and convert them into a single output, and this job usually takes place right where the axon begins (PMID 39480263). This very first section is the place that makes the final call on whether the incoming signals are plentiful enough to pass along to the next step (PMID 39480263). In this spot, small channels through which sodium moves are packed more densely than on the cell body, so the threshold for triggering a signal is low (PMID 34440880).

Action potentials are brief electrical signals in which the electrical state of a neuron's membrane momentarily flips and then returns, traveling all the way along the axon. Cells that produce these signals, such as neurons, muscle cells, and heart muscle cells, are densely packed with sodium channels that open depending on voltage, and these channels are required for action potentials to occur (PMID 39901031). These same channels are also targets for drugs, so medications that selectively target specific sodium channels are being developed for epilepsy, heart disease, and pain (PMID 39901031).

The way an action potential travels along the axon resembles a burning fuse rather than an electric current flowing inside a wire. When one spot on the membrane flips, that force immediately flips the spot right next to it, and the signal advances as it regenerates spot by spot. Because of this, even when the signal travels a long way, it does not weaken and reaches the end at the exact same size. There is also a difference from a fuse. A fuse is finished once it burns through, but the axon's membrane immediately returns to its original state and can generate signals again.

Inside a single neuron, signals travel as electricity. If the signals coming in at the start of the axon are judged to be sufficient, an action potential is triggered, and that signal travels all the way to the end of the axon, regenerating at each spot along the way.

Fire That Jumps from Node to Node

Many axons are wrapped in multiple layers of insulation. Oligodendrocytes are glial cells that wrap axons with insulation in the brain. Myelin is a sheath made by glial cells wrapping their membranes multiple times around an axon, which prevents electricity from leaking and speeds up signals. In the brain, oligodendrocytes make myelin, and in nerves extending to the limbs, a different type of glial cell does (PMID 35908945).

Myelin does not cover the axon without gaps. There are short exposed nodes between the wrapped segments, and sodium channels are clustered at these nodes (PMID 35908945). The signal leaps over the wrapped segments, jumping from node to node, and this leaping transmission greatly increases the speed of the signal (PMID 25288117, PMID 31760642). If you compare it to a fuse, it is a fuse with a casing put on in spots so that the fire catches again only at the exposed nodes.

Signals must arrive on time. To refine movement and combine various sensations into one, arrival at the exact time is necessary, and myelin not only maximizes speed but also serves as a means to evenly match the arrival times between neurons (PMID 23820043). However, how that regulation takes place is not yet well understood (PMID 23820043).

The glial cells that make myelin do not just provide insulation. For myelinated axons to remain intact for a long time, metabolic substances and growth factors supplied by glial cells are necessary (PMID 25288117). Therefore, when myelin disappears, axons cannot work properly, which can reduce nerve function and lead to disease (PMID 38377028), and there are diseases where myelin breaks down, such as multiple sclerosis (PMID 31066630).

Myelin makes signals fast by letting them jump from node to node, and it nourishes the axon beneath it.

The Gap Is Usually Crossed with Chemicals

The electrical signal that reaches the end of the axon usually cannot pass directly to the next cell. This is because there is a narrow gap between the two cells. A synapse is the junction where one nerve cell passes a signal to the next nerve cell. At these synapses, electrical signals are converted into chemical signals.

When an action potential reaches the end of the axon, calcium enters that end. Calcium causes small vesicles to fuse with the cell membrane, and the neurotransmitters contained in the vesicles spill out into the gap. This process takes less than 1/1,000 of a second (PMID 24183019). A neurotransmitter is a chemical substance that nerve cells release to transmit signals to other cells, and it usually crosses the synapse to the cell on the other side. The receiving cell may be another nerve cell or another cell throughout the body (PMID 18064409). The emptied vesicle is retrieved and refilled, which allows the synapse to send signals rapidly over and over (PMID 15217342).

The cell on the other side of the gap receives the neurotransmitter with a receptor. A receptor is a protein located on a cell that recognizes and catches only specific substances. When a neurotransmitter binds to the receptor of the receiving cell, that cell reacts (PMID 38151329). The signal crossing the synapse in this way travels only within the junction, and usually finishes in about 1/1,000 of a second (PMID 38789677).

A fire traveling along a fuse cannot cross water. So, at the water's edge, a ferryboat is launched, and when the boat reaches the landing on the other side, it either adds strength so that the fuse on the opposite side catches fire, or holds it back so that the fire does not catch. Whether the fire actually catches is determined by summing up all the boats that reached the various landings. The neurotransmitter is the ferryboat, and the receptor is the landing on the other side. The analogy holds even to the point that each landing is designated to receive specific boats. The actual gap is invisibly narrow, and the substance spreads and crosses that narrow gap, unlike a boat that is rowed with oars.

A third cell is also attached to this junction. Astrocytes are considered part of the synapse, receiving signals sent by nerve cells and then sending them back to regulate their activity (PMID 36799296).

Inside a single nerve cell, the signal travels as electricity, and the gap between cells is usually crossed with a chemical substance called a neurotransmitter.

Signals That Push, Signals That Hold

There are two main neurotransmitters in the brain (PMID 40066661). Glutamate is a neurotransmitter that pushes the receiving cell toward firing an action potential. GABA is a neurotransmitter that holds the receiving cell back from firing action potentials as easily. The main substance in charge of excitation in the brain is glutamate, and GABA, the main substance in charge of inhibition, counters its action. The balance between these two is essential for the brain to work normally (PMID 19275596).

Pushing signals and holding signals flow into a single neuron together, and the neuron gathers these signals and turns them into a single output (PMID 39480263). If the sum is sufficient at the spot where the axon begins, an action potential occurs; if it falls short, it does not occur (PMID 39480263). The output of a single neuron depends on how the pushing side and the holding side are mixed.

The released substances do not simply remain in the gap. Astrocytes collect glutamate and GABA from the synapse, convert them into other substances, and return them to neurons, which then use them as raw materials to make glutamate and GABA again (PMID 40066661). Glial cells also release these same substances on their own. Stimulated glial cells release substances like glutamate and GABA to regulate surrounding synaptic signals (PMID 26084688).

Discrepancies in this balance are also studied in connection with disease. One review summarizing research on mouse brain development lists the imbalance between excitation and inhibition and changes in glial cell numbers as signature features of disorders like schizophrenia, bipolar disorder, and autism (PMID 29413892). This review is an article dealing with the process of how the brain grows, not an article uncovering why these diseases occur.

Whether a neuron will fire a signal is determined by the sum of the pushing signals and the holding signals, and the brain operates upon that balance.

What Dopamine and Serotonin Do

We often hear phrases like "dopamine is exploding" or "serotonin creates happiness." Dopamine is a neurotransmitter produced by nerve cells deep within the brain and sent to wide areas, and it is involved in movement, learning, and motivation. Serotonin is a neurotransmitter produced by nerve cells deep in the lower part of the brain and sent to various parts of the brain, and it is involved in multiple states such as sleep, mood, and appetite.

These two substances do work different from glutamate or GABA. Substances like dopamine and serotonin take charge of the modulating side of things in the brain and are involved across many neural circuits (PMID 19275596). Their way of working is also different. Unlike transmission within a single synapse that finishes in a 1,000th of a second, dopamine and serotonin mainly work by spreading into the surrounding area outside the synapse without relying on synaptic contact, and this method is less precise (PMID 38789677). Because these substances work broadly across many circuits, the picture of pairing one dopamine to one pleasure and one serotonin to one happiness cannot capture this breadth. There are still many parts we do not yet know about the exact mechanisms by which these spreading signals reach, how far they go, and how long they last (PMID 38789677).

Neurotransmitters are essential for various tasks such as learning and memory, sleep cycles, body movement, and hormone regulation (PMID 19275596). Dopamine also steps in when the strength of a connection changes. One review summarizing studies that peeked into brain circuits experimentally notes that dopamine signals are needed during the late-consolidation stage of synaptic strengthening (PMID 28093558).

Knowing how these substances are spread and received helps us understand how therapeutic drugs and abused drugs alter these signals (PMID 38789677).

Dopamine and serotonin are neurotransmitters that broadly modulate the activity of nerve cells across multiple circuits, and the picture of pairing one substance with one emotion fails to capture that breadth.

Connections That Change When Used

The first time we walk an unfamiliar path, we fumble along with a map, but after going a few times, the route comes to mind on its own. When explaining where these changes remain in the brain, the place most often looked at is the connections between cells. Synaptic plasticity is the property by which the strength with which signals cross a synapse becomes stronger or weaker depending on how that synapse was used.

There are at least six ways synapses change their strength, with long-lasting strengthening and long-lasting weakening being the most representative (PMID 28093558). Long-lasting strengthening has been the most studied model for explaining how memories are left at the cellular level (PMID 30523578). However, one review notes that how changes in connection strength translate into learning and memory is not yet solved (PMID 38151329).

The speed of connections can also change. Myelin was once thought of as a fixed cover once made, but it has become known that it is replaced with new myelin throughout life and that existing myelin is refined again according to neural activity and experience (PMID 38773349). In humans, myelin formation continues long after adulthood, and evidence that myelin can vary according to experience and neural activity has emerged from fish, rodents, monkeys, and humans, and it is expected that when the detailed structure of myelin changes, the speed of signals will also change (PMID 26282119).

Glial cells also join in this change. The activity of astrocytes has been linked to changes in synaptic strength and learning. In experiments intentionally suppressing or reducing brain cells, suppressing astrocytes caused memory problems, reducing microglia altered learning and memory, and the effect differed depending on the developmental stage (PMID 39358030). The abstract of this review does not reveal the animals tested, so whether the same applies to the human brain cannot be said from this result alone. This review notes that the exchanges between neurons and glial cells are a field with many questions yet to be solved (PMID 39358030).

Connections between neurons change in strength according to use, myelin is newly replaced and refined throughout life, and these changes are thought to alter signal speeds.

The Gateway to the Brain

The medicine you swallow enters your blood and circulates throughout your body. Yet most substances carried in the blood cannot pass directly into the brain (PMID 15207256). The blood-brain barrier is a border formed by tightly joined cells making up the walls of tiny blood vessels in the brain, blocking substances in the blood from carelessly crossing over into the brain.

At the core of the barrier are tight junctions packing the space between vascular wall cells. Other cells and the endfeet of astrocytes wrap around the vascular wall, and while astrocytes are important for building and maintaining these junctions, it is thought that astrocytes themselves do not act as the barrier (PMID 15207256). The barrier does not merely block things. Controlling the transport of substances entering and leaving the brain is also part of the barrier's job (PMID 24309662).

There is a reason it blocks things to this extent. Nerve signals inside the brain require a very evenly regulated environment to travel back and forth properly (PMID 19664713). The blood-brain barrier protects the brain from harmful substances in the blood, supplies the brain with nutrients, and pumps harmful substances back out from the brain into the blood (PMID 18040800).

This same barrier also blocks medicines. Because the barrier does not easily let substances in, it is difficult to deliver medicines to the brain (PMID 18040800), and this makes developing drugs for brain diseases extremely difficult (PMID 40127880). Methods to alter the shape of drugs so they can pass through the barrier, alongside new techniques using focused ultrasound to temporarily open the barrier, are being researched (PMID 31790711).

When the barrier breaks down, inflammation and damage to nerve cells can follow in the brain (PMID 24309662), and the breakdown of the barrier or altered transport plays an important role in many brain diseases, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis (PMID 18040800).

The blood-brain barrier protects the environment where nerve signals travel, and for that same reason, it keeps many medicines from easily reaching the brain.

Until We Call a Name, Again

We return to the first scene. While you recognize a face across the street, if you picture what happens in a single nerve cell inside your head, it looks like this.

Signals sent by multiple cells arrive together at the dendrites. The push signals carried by glutamate and the hold signals carried by GABA are mixed together (PMID 19275596). The place where the axon begins sorts that sum, and if it is sufficient, an action potential occurs (PMID 39480263). If the axon of this cell is wrapped in myelin, the action potential runs, leaping from node to node (PMID 35908945). When it reaches the end of the axon, calcium enters, and in less than 1,000ths of a second, neurotransmitters pour into the gap (PMID 24183019). The receptors of the cell on the other side receive them so that that cell reacts (PMID 38151329), and the substances remaining in the gap are cleared away by astrocytes, converted into other substances, and returned to the nerve cell (PMID 40066661). All of these things happen within an environment steadily guarded by the blood-brain barrier (PMID 19664713).

The work of running along a fuse and crossing the gap by ferry overlaps countless times while you call a name once. That the strength of a connection can change depending on its use is what cellular-level research has shown (PMID 28093558), and how that change becomes the memory of a "known face" is still an unsolved question (PMID 38151329).

Where to Look Further

How changes in the strength of connection become learning and memory, and by what mechanism widely spreading signals like dopamine and serotonin work, are still open questions.

Where these signals gather and work in the brain is continued in "The Map of the Brain — Neighborhoods with Their Own Jobs, a City Joined by Roads". The long paths connecting the brain and body are covered by "The Spinal Cord and Peripheral Nerves — A Trunk Line, and a Loop That Turns Back Halfway", and a disease where nerve cells slowly damage and shrink is covered by "What Is Dementia? — Snow That Settles Without a Sound, a Branch Beginning to Bend".

The work of rewiring connections after the brain is injured is continued in "Neuroplasticity — A Brain That Builds New Roads Beside the Broken Ones". Hormones, another type of signal that travels far via the blood, are covered by "How Hormones Work — Letters Only the Addressee Reads, Replies That Say Stop". Parkinson's disease, headaches and migraines, epilepsy, and numbness and peripheral neuropathy are topics to be covered ahead in this series.

Source Papers

• "The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting." (2016) — PMID 27187682 — For half a century, it was believed there were 100 billion neurons and 1 trillion glial cells (a 10:1 ratio), but new counting methods showed a glia-to-neuron ratio of less than 1:1 and fewer than 100 billion glial cells, while histological data also consistently supported a 1:1 ratio and 40 billion to 130 billion.
• "Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain." (2009) — PMID 19226510 — Adult male brains average 86.1 billion ± 8.1 billion neurons and 84.6 billion ± 9.8 billion non-neuronal cells (using the isotropic fractionator method).
• "The glia/neuron ratio: how it varies uniformly across brain structures and species and what that means for brain physiology and evolution." (2014) — PMID 24807023 — The conventional notion that "glial cells make up 90% of human brain cells" is incorrect.
• "Neuroglial Transmission." (2015) — PMID 26084688 — Glial cells, once called the "glue" filling the spaces between neurons, participate in signals by releasing glutamate, GABA, ATP, and lactate upon stimulation to modulate synaptic signals and diffuse over longer distances.
• "Glia as architects of central nervous system formation and function." (2018) — PMID 30309945 — Glial cells account for about half of the cells in the central nervous system, and while long considered static bystanders, they coordinate nearly every aspect of its formation and function.
• "The Concept of Neuroglia." (2019) — PMID 31583582 — The functions of glial cells are grouped into homeostasis maintenance (water, ions, neurotransmitters, metabolites, and fuel) and defense (against microorganisms and others).
• "Neuron-Glial Interactions: Implications for Plasticity, Behavior, and Cognition." (2024) — PMID 39358030 — Astrocytes are the most abundant glial cells in the central nervous system, hippocampal astrocyte inhibition causes memory deficits, astrocyte activity is linked to synaptic strength changes and learning, microglial reduction affects learning and memory (in a developmental stage-dependent manner), and neuron-glial interactions require further study.
• "Microglia and neuroinflammation: function, heterogeneity, and crosstalk." (2026) — PMID 42243476 — Microglia are resident innate immune cells of the central nervous system, handling immune surveillance, injury response, and synaptic pruning, and acting as neuroprotective or toxic depending on the context.
• "Axon initial segment structure and function in health and disease." (2025) — PMID 39480263 — Neurons integrate synaptic inputs and convert them into action potentials, which usually happens at the axon initial segment, acting as the final arbiter determining whether inputs are sufficient to trigger an action potential.
• "Pathophysiological Roles of Abnormal Axon Initial Segments in Neurodevelopmental Disorders." (2021) — PMID 34440880 — The axon initial segment has a higher density of sodium channels than the cell body, lowering the action potential initiation threshold.
• "Voltage-gated sodium channels in excitable cells as drug targets." (2025) — PMID 39901031 — Nerve, muscle, and cardiac cells generate action potentials due to a high density of voltage-gated sodium channels, and subtype-selective drugs are being developed for epilepsy, heart disease, and pain.
• "[Introduction to Myelin Research]." (2022) — PMID 35908945 — Myelin is a multi-layered membrane formed by oligodendrocytes in the central nervous system and Schwann cells in the periphery, enabling fast propagation via saltatory conduction, with sodium channels clustered at the nodes.
• "Myelination of the nervous system: mechanisms and functions." (2014) — PMID 25288117 — Myelination enables fast saltatory conduction, and the long-term integrity of myelinated axons relies on metabolites and trophic factors supplied by glial cells.
• "Oligodendrocyte Physiology Modulating Axonal Excitability and Nerve Conduction." (2019) — PMID 31760642 — Myelin made by oligodendrocytes dramatically increases conduction speed, and white matter plasticity is involved in learning and memory.
• "Regulation of conduction time along axons." (2014) — PMID 23820043 — Motor control, sensory integration, and cognition require precise regulation of conduction speed, and myelination not only maximizes speed but also serves as a means to systematically regulate conduction times between regions, though the mechanisms remain largely unknown.
• "Physical Exercise Counteracts Aging-Associated White Matter Demyelination Causing Cognitive Decline." (2024) — PMID 38377028 — Demyelination can cause axonal dysfunction, leading to neurological damage and disease (this article cites only this sentence).
• "Myelin in the Central Nervous System: Structure, Function, and Pathology." (2019) — PMID 31066630 — In addition to saltatory conduction, myelin has functions such as metabolic support, and it is disrupted in various diseases like multiple sclerosis.
• "Neurotransmitter release: the last millisecond in the life of a synaptic vesicle." (2013) — PMID 24183019 — Calcium entering nerve terminals during an action potential triggers vesicle fusion and neurotransmitter release in less than a millisecond.
• "Neurotransmitter release." (2008) — PMID 18064409 — Neurotransmitters transmit signals between neurons and between neurons and peripheral target cells, and synaptic transmission is fast and local, whereas neuromodulators regulate the state of entire regions.
• "The synaptic vesicle cycle." (2004) — PMID 15217342 — For fast and repeated release, synaptic vesicles undergo a cycle of fusion, retrieval, and recycling.
• "Phospholipase Modulation of Synaptic Membrane Landscape: Driving Force Behind Memory Formation?" (2024) — PMID 38151329 — Postsynaptic responses occur after neurotransmitters bind to specialized receptors, and how connected brains learn and remember through synaptic plasticity remains an open question.
• "Mechanisms of neuromodulatory volume transmission." (2024) — PMID 38789677 — While synaptic transmission is confined to contact sites and occurs within about a millisecond, volume transmission—the primary mode for monoamines and neuropeptides—does not rely on synaptic contacts, is less precise, and its mechanisms and spatiotemporal scope are not well understood, which is needed to understand the action of therapeutic and abused drugs.
• "Interactions of glial cells with neuronal synapses, from astrocytes to microglia and oligodendrocyte lineage cells." (2023) — PMID 36799296 — The "tripartite synapse" concept: astrocytes, as part of the synapse, receive neural signals and then modulate neural activity through feedback.
• "The Glutamate/GABA-Glutamine Cycle: Insights, Updates, and Advances." (2025) — PMID 40066661 — Glutamate and GABA are major neurotransmitters; astrocytes take them up at synapses, convert them into glutamine, and pass them to neurons, which use them as raw materials for resynthesis.
• "Neuro-transmitters in the central nervous system & their implication in learning and memory processes." (2009) — PMID 19275596 — Neurotransmitters are essential for learning, memory, sleep cycles, movement, and hormone regulation, with glutamate being the primary excitatory and GABA the primary inhibitory neurotransmitter, and their balance is essential for normal brain function, while acetylcholine, serotonin, and catecholamines (such as dopamine) have modulatory functions spanning multiple circuits.
• "Mechanisms of Cortical Differentiation." (2018) — PMID 29413892 — A review of mouse neocortex development research showing that an imbalance in excitation and inhibition or changes in glial cell numbers are hallmark features of disorders like schizophrenia, bipolar disorder, and autism.
• "Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling." (2017) — PMID 28093558 — Synapses exhibit at least six types of plasticity with different mechanisms (long-term potentiation, long-term depression, short-term potentiation, scaling, etc.), and late long-term potentiation requires dopamine signaling.
• "Molecular Mechanisms of Early and Late LTP." (2019) — PMID 30523578 — Long-term potentiation (LTP) is the most heavily studied cellular model of memory.
• "Dynamics of mature myelin." (2024) — PMID 38773349 — Although myelin was long considered a stable structure, entire membranes are replaced throughout life, and even mature myelin is structurally refined in response to neural activity, behavioral experience, and injury.
• "Myelin plasticity in the central nervous system." (2016) — PMID 26282119 — In humans, myelination continues into adulthood, and evidence from zebrafish, rodents, non-human primates, and humans suggests that myelination can be sensitive to experience, with myelin microstructure changes expected to affect conduction velocity.
• "The blood-brain barrier: an overview: structure, regulation, and clinical implications." (2004) — PMID 15207256 — The blood-brain barrier is a diffusion barrier preventing most compounds from entering the brain from the blood, with tight junctions between vascular endothelial cells playing a key role, while astrocyte endfeet are important for inducing and maintaining tight junctions although they are not thought to constitute the barrier function themselves.
• "Structure and function of the blood-brain barrier." (2010) — PMID 19664713 — Neural signals within the central nervous system require a highly controlled microenvironment, maintained by the physical barrier of tight junctions and the transport barrier of membrane transporters, and new drug development must consider the characteristics of this barrier.
• "Blood-brain barrier: structural components and function under physiologic and pathologic conditions." (2006) — PMID 18040800 — The blood-brain barrier protects the brain from toxic substances in the blood, supplies nutrients, and returns harmful substances to the blood, while its limited permeability makes therapeutic delivery difficult, and barrier breakdown and transport alterations are important in the pathogenesis of various diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis.
• "Recent advances in blood-brain barrier-on-a-chip models." (2025) — PMID 40127880 — The healthy barrier blocks the passage of most biomolecules, making drug development extremely difficult.
• "The blood-brain barrier: Physiology and strategies for drug delivery." (2020) — PMID 31790711 — Drug formulation changes and invasive or non-invasive bypass strategies, including new techniques using focused ultrasound to safely and reversibly open the barrier.
• "Development, maintenance and disruption of the blood-brain barrier." (2013) — PMID 24309662 — When the barrier breaks down, neuroinflammation and neurodegeneration can occur.