Our blood-brain barrier stops bugs and toxins getting to our brain. Here’s how it works

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Our brain is an extremely complex and delicate organ. Our body fiercely protects it by holding onto things that help it and keeping harmful things out, such as bugs that can cause infection and toxins.

It does that though a protective layer called the blood-brain barrier. Here’s how it works, and what it means for drug design.

The Conversation, Rattiya Thongdumhyu/Shutterstock, Petr Ganaj/Pexels

First, let’s look at the circulatory system

Adults have roughly 30 trillion cells in their body. Every cell needs a variety of nutrients and oxygen, and they produce waste, which needs to be taken away.

Our circulatory system provides this service, delivering nutrients and removing waste.

A fenestrated capillary
Fenestrated capillaries let nutrients and waste pass through. Vectormine/Shutterstock

Where the circulatory system meets your cells, it branches down to tiny tubes called capillaries. These tiny tubes, about one-tenth the width of a human hair, are also made of cells.

But in most capillaries, there are some special features (known as fenestrations) that allow relatively free exchange of nutrients and waste between the blood and the cells of your tissues.

It’s kind of like pizza delivery

One way to think about the way the circulation works is like a pizza delivery person in a big city. On the really big roads (vessels) there are walls and you can’t walk up to the door of the house and pass someone the pizza.

But once you get down to the little suburban streets (capillaries), the design of the streets means you can stop, get off your scooter and walk up to the door to deliver the pizza (nutrients).

We often think of the brain as a spongy mass without much blood in it. In reality, the average brain has about 600 kilometres of blood vessels.

The difference between the capillaries in most of the brain and those elsewhere is that these capillaries are made of specialised cells that are very tightly joined together and limit the free exchange of anything dissolved in your blood. These are sometimes called continuous capillaries.

Continuous capillary
Continuous capillaries limit the free exchange of anything dissolved in your blood. Vectormine/Shutterstock

This is the blood brain barrier. It’s not so much a bag around your brain stopping things from getting in and out but more like walls on all the streets, even the very small ones.

The only way pizza can get in is through special slots and these are just the right shape for the pizza box.

The blood brain barrier is set up so there are specialised transporters (like pizza box slots) for all the required nutrients. So mostly, the only things that can get in are things that there are transporters for or things that look very similar (on a molecular scale).

The analogy does fall down a little bit because the pizza box slot applies to nutrients that dissolve in water. Things that are highly soluble in fat can often bypass the slots in the wall.

Why do we have a blood-brain barrier?

The blood brain barrier is thought to exist for a few reasons.

First, it protects the brain from toxins you might eat (think chemicals that plants make) and viruses that often can infect the rest of your body but usually don’t make it to your brain.

It also provides protection by tightly regulating the movement of nutrients and waste in and out, providing a more stable environment than in the rest of the body.

Lastly, it serves to regulate passage of immune cells, preventing unnecessary inflammation which could damage cells in the brain.

What it means for medicines

One consequence of this tight regulation across the blood brain barrier is that if you want a medicine that gets to the brain, you need to consider how it will get in.

There are a few approaches. Highly fat-soluble molecules can often pass into the brain, so you might design your drug so it is a bit greasy.

Person holds tablet and glass
The blood-brain barrier stops many medicines getting into the brain. Ron Lach/Pexels

Another option is to link your medicine to another molecule that is normally taken up into the brain so it can hitch a ride, or a “pro-drug”, which looks like a molecule that is normally transported.

Using it to our advantage

You can also take advantage of the blood brain barrier.

Opioids used for pain relief often cause constipation. They do this because their target (opioid receptors) are also present in the nervous system of the intestines, where they act to slow movement of the intestinal contents.

Imodium (Loperamide), which is used to treat diarrhoea, is actually an opioid, but it has been specifically designed so it can’t cross the blood brain barrier.

This design means it can act on opioid receptors in the gastrointestinal tract, slowing down the movement of contents, but does not act on brain opioid receptors.

In contrast to Imodium, Ozempic and Victoza (originally designed for type 2 diabetes, but now popular for weight-loss) both have a long fat attached, to improve the length of time they stay in the body.

A consequence of having this long fat attached is that they can cross the blood-brain barrier, where they act to suppress appetite. This is part of the reason they are so effective as weight-loss drugs.

So while the blood brain barrier is important for protecting the brain it presents both a challenge and an opportunity for development of new medicines.

Sebastian Furness, ARC Future Fellow, School of Biomedical Sciences, The University of Queensland

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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  • Tinnitus: Quieting The Unwanted Orchestra In Your Ears

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    Tinnitus—When a “minor” symptom becomes disruptive

    Tinnitus (typically: ringing in the ears) is often thought of less as a condition in and of itself, and more a symptom related to other hearing-related conditions. Paradoxically, it can be associated with hearing loss as well as with hyperacusis (hearing supersensitivity, which sounds like a superpower, but can be quite a problem too).

    More than just ringing

    Tinnitus can manifest not just as ringing, but also as whistling, hissing, pulsing, buzzing, hooting, and more.

    For those who don’t suffer from this, it can seem very trivial; for those who do… Sometimes it can seem trivial too!

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    What causes it?

    First let’s note, tinnitus can be acute or chronic. So, some of these things may just cause tinnitus for a while, whereas some may give you tinnitus for life. In some cases, it depends on how long the thing in question persisted for.

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    • Earplugs or noise-canceling headphones—while tinnitus is an internal sound, not external, it often has to do with some part(s) of your ears being unduly sensitive, so giving them less stimulus may ease the tinnitus that occurs in reaction to external noise.
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    • Hearing aids—counterintuitively, for some people whose tinnitus has developed in response to hearing loss, hearing aids can help bring things “back to normal” and eliminate tinnitus in the process.
    • Customized sound machines—if you have the resources to get fancy, science currently finds this to be best of all. They work like white noise, but are tailored to your specific tinnitus.

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    Some children show signs of perfectionism from early on. Young children might become frustrated and rip up their drawing if it’s not quite right. Older children might avoid or refuse to do homework because they’re afraid to make a mistake.

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    What is perfectionism?

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    2. perfectionistic concerns: worry about being able to meet high standards, and self-criticism about performance.

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    Parents who are perfectionistic themselves can also model this to their children.

    So, how can we walk the line between supporting our child’s interests and helping them to achieve their potential, without pressuring them and increasing the risk of negative outcomes?

    Give them space to grow

    A great metaphor is the gardener versus the carpenter described by psychology professor Alison Gopnik.

    Instead of trying to build and shape our children by controlling them and their environment (like a carpenter), parents can embrace the spirit of the gardener – providing lots of space for children to grow in their own direction, and nourishing them with love, respect and trust.

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    We can’t control who they become, so it’s better to sit back, enjoy the ride, and look forward to watching the person they grow into.

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    Set realistic goals

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    Talk aloud practices can help children to see that we “walk the walk”. For example, if you burn dinner you could reflect:

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    Manage stress and negative emotions

    Some children and adolescents have a natural tendency towards perfectionism. Rather than trying to control their behaviour, we can provide gentle, loving support.

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    There is also evidence that getting active outdoors in nature can promote children’s coping skills, emotion regulation and cognitive development.

    Elizabeth Westrupp, Associate Professor in Psychology, Deakin University; Gabriella King, Associate Research Fellow, Deakin University, and Jade Sheen, Associate Professor, School of Psychology, Deakin University

    This article is republished from The Conversation under a Creative Commons license. Read the original article.

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  • Unbroken – by Dr. MaryCatherine McDonald

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  • Escape From The Clutches Of Shame

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    We’ve written before about managing various emotions, including “negative” ones. We put that in “scare quotes” because they also all have positive aspects, that are just generally overshadowed by the fact that the emotions themselves are not pleasant. But for example…

    We evolved our emotions, including the “negative” ones, for our own benefit as a species:

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    The Off-Button For Your Brain

    While it’s generally considered good to process feelings instead of putting them aside, the fact is that sometimes we have to hold it together while we do something, such that we can later have an emotional breakdown at a convenient time and place, instead of the supermarket or bank or office or airport or while entertaining houseguests or… etc.

    Today, though, we’re not putting things aside, for the most part (though we will get to that too).

    We’ll be dealing with shame, which is closely linked to the guilt we mentioned in that list there.

    See also: Reconsidering the Differences Between Shame and Guilt

    Shame’s purpose

    Shame’s purpose is to help us (as a community) avoid anti-social behavior for which we might be shamed, and thus exiled from the in-group. It helps us all function better together, which is how we thrive as a species.

    Shame, therefore, is often assumed to be something we can (and possibly should) use to ensure that we (ourselves and/or others) “do the right thing”.

    But there’s a catch…

    Shame only works negatively

    You may be thinking “well duh, it’s a negative emotion”, but this isn’t about negativity in the subjective sense, but rather, positive vs negative motivation:

    • Positive motivation: motivation that encourages us to do a given thing
    • Negative motivation: motivation that encourages us to specifically not do a given thing

    Shame is only useful as a negative motivation, i.e., encouraging us to specifically not do a given thing.

    Examples:

    • You cannot (in any way that sticks, at least) shame somebody into doing more housework.
    • You can, however, shame somebody out of drinking and driving.

    This distinction matters a lot when it comes to how we are with our children, or with our employees (or those placed under us in a management structure), or with people who otherwise look to us as leaders.

    It also matters when it comes to how we are with ourselves.

    Here’s a paper about this, by the way, with assorted real-world examples:

    The negative side of motivation: the role of shame

    From those examples, we can see that attempts to shame someone (including oneself) into doing something positive will generally not only fail, they will actively backfire, and people (including oneself) will often perform worse than pre-shaming.

    Looking inwards: healthy vs unhealthy shame

    Alcoholics Anonymous and similar programs use a degree of pro-social shame to help members abstain from the the act being shamed.

    Rather than the unhelpful shame of exiling a person from a group for doing a shameful thing, however, they take an approach of laying out the shame for all to see, feeling the worst of it and moving past it, which many report as being quite freeing emotionally while still [negatively] motivational to not use the substance in question in the future (and similar for activity-based addictions/compulsions, such as gambling, for example).

    As such, if you are trying to avoid doing a thing, shame can be a useful motivator. So by all means, if it’s appropriate to your goals, tell your friends/family about how you are now quitting this or that (be it an addiction, or just something generally unhealthy that you’d like to strike off your regular consumption/activity list).

    You will still be tempted! But the knowledge of the shame you would feel as a result will help keep you from straying into that temptation.

    If you are trying to do a thing, however, (even something thought of in a negative frame, such as “lose weight”), then shame is not helpful and you will do best to set it aside.

    You can shame yourself out of drinking sodas (if that’s your plan), but you can’t shame yourself into eating healthy meals. And even if your plan is just shaming yourself out of eating unhealthy food… Without a clear active positive replacement to focus on instead, all you’ll do there is give yourself an eating disorder. You’ll eat nothing when people are looking, and then either a) also eat next to nothing in private or else b) binge in secret, and feel terrible about yourself, neither of which are any good for you whatsoever.

    Similarly, you can shame yourself out of bed, but you can’t shame yourself into the gym:

    Is there positive in the negative? Understanding the role of guilt and shame in physical activity self-regulation

    Let it go

    There are some cases, especially those where shame has a large crossover with guilt, that it serves no purpose whatsoever, and is best processed and then put aside.

    For example, if you did something that you are ashamed of many years ago, and/or feel guilty about something that you did many years ago, but this is not an ongoing thing for you (i.e., it was a one-off bad decision, or a bad habit that have now long since dropped), then feeling shame and/or guilt about that does not benefit you or anyone else.

    As to how to process it and put it aside, if your thing harmed someone else, you could see if there’s a way to try to make amends (even if without confessing ill, such as by acting anonymously to benefit the person/group you harmed).

    And then, forgive yourself. Regardless of whether you feel like you deserve it. Make the useful choice, that better benefits you, and by extension those around you.

    If you are religious, you may find that of help here too. We’re a health science publication not a theological one, but for example: Buddhism preaches compassion including for oneself. Judaism preaches atonement. Christianity, absolution. For Islam, mercy is one of the holiest ideals of the religion, along with forgiveness. So while religion isn’t everyone’s thing, for those for whom it is, it can be an asset in this regard.

    For a more worldly approach:

    To Err Is Human; To Forgive, Healthy (Here’s How To Do It) ← this goes for when the forgiveness in question is for yourself, too—and we do write about that there (and how)!

    Take care!

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