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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  • Staying Sane In A Hyper-Connected World

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  • Accidental falls in the older adult population: What academic research shows

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    Accidental falls are among the leading causes of injury and death among adults 65 years and older worldwide. As the aging population grows, researchers expect to see an increase in the number of fall injuries and related health spending.

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    Falls in older adults

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    In addition, “sometimes people restrict their movement and activities after a fall, which they think is protective, but leads to further functional declines and increases in fall risk,” she adds.

    Factors that can cause a fall include:

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    • Loss of strength, balance, and mobility with age, which can lessen one’s ability to prevent a fall when slipping or tripping.
    • Fear of falling, which usually indicates decreased balance.
    • Conditions such as diabetes, heart disease, or problems with nerves or feet that can affect balance.
    • Conditions like incontinence that cause rushed movement to the bathroom.
    • Cognitive impairment or certain types of dementia.
    • Unsafe footwear such as backless shoes or high heels.
    • Medications or medication interactions that can cause dizziness or confusion.
    • Safety hazards in the home or outdoors, such as poor lighting, steps and slippery surfaces.

    Related Research

    Nonfatal and Fatal Falls Among Adults Aged ≥65 Years — United States, 2020–2021
    Ramakrishna Kakara, Gwen Bergen, Elizabeth Burns and Mark Stevens. Morbidity and Mortality Weekly Report, September 2023.

    Summary: Researchers analyzed data from the 2020 Behavioral Risk Factor Surveillance System — a landline and mobile phone survey conducted each year in all 50 U.S. states and the District of Columbia — and data from the 2021 National Vital Statistics System to identify patterns of injury and death due to falls in the U.S. by sex and state for adults 65 years and older. Among the findings:

    • The percentage of women who reported falling was 28.9%, compared with 26.1% of men.
    • Death rates from falls were higher among white and American Indian or Alaska Native older adults than among older adults from other racial and ethnic groups.
    • In 2020, the percentage of older adults who reported falling during the past year ranged from 19.9% in Illinois to 38.0% in Alaska. The national estimate for 18 states was 27.6%.
    • In 2021, the unintentional fall-related death rate among older adults ranged from 30.7 per 100,000 older adults in Alabama to 176.5 in Wisconsin. The national estimate for 26 states was 78.

    “Although common, falls among older adults are preventable,” the authors write. “Health care providers can talk with patients about their fall risk and how falls can be prevented.”

    Trends in Nonfatal Falls and Fall-Related Injuries Among Adults Aged ≥65 Years — United States, 2012-2018
    Briana Moreland, Ramakrishna Kakara and Ankita Henry. Morbidity and Mortality Weekly Report, July 2020.

    Summary: Researchers compared data from the 2018 Behavioral Risk Factor Surveillance System. Among the findings:

    • The percentage of older adults reporting a fall increased from 2012 to 2016, then slightly decreased from 2016 to 2018.
    • Even with this decrease in 2018, older adults reported 35.6 million falls. Among those falls, 8.4 million resulted in an injury that limited regular activities for at least one day or resulted in a medical visit.

    “Despite no significant changes in the rate of fall-related injuries from 2012 to 2018, the number of fall-related injuries and health care costs can be expected to increase as the proportion of older adults in the United States grows,” the authors write.

    Understanding Modifiable and Unmodifiable Older Adult Fall Risk Factors to Create Effective Prevention Strategies
    Gwen Bergen, et al. American Journal of Lifestyle Medicine, October 2019.

    Summary: Researchers used data from the 2016 U.S. Behavioral Risk Factor Surveillance System to better understand the association between falls and fall injuries in older adults and factors such as health, state and demographic characteristics. Among the findings:

    • Depression had the strongest association with falls and fall injuries. About 40% of older adults who reported depression also reported at least one fall; 15% reported at least one fall injury.
    • Falls and depression have several factors in common, including cognitive impairment, slow walking speed, poor balance, slow reaction time, weakness, low energy and low levels of activity.
    • Other factors associated with an increased risk of falling include diabetes, vision problems and arthritis.

    “The multiple characteristics associated with falls suggest that a comprehensive approach to reducing fall risk, which includes screening and assessing older adult patients to determine their unique, modifiable risk factors and then prescribing tailored care plans that include evidence-based interventions, is needed,” the authors write.

    Health care use and cost

    In addition to being the leading cause of injury, falls are the leading cause of hospitalization in older adults. Each year, about 3 million older adults visit the emergency department due to falls. More than 1 million get hospitalized.

    In 2021, falls led to more than 38,000 deaths in adults 65 and older, according to the CDC.

    The annual financial medical toll of falls among adults 65 years and older is expected to be more than $101 billion by 2030, according to the National Council on Aging, an organization advocating for older Americans.

    Related research

    Healthcare Spending for Non-Fatal Falls Among Older Adults, USA
    Yara K. Haddad, et al. Injury Prevention, July 2024.

    Summary: In 2015, health care spending related to falls among older adults was roughly $50 billion. This study aims to update the estimate, using the 2017, 2019 and 2021 Medicare Current Beneficiary Survey, the most comprehensive and complete survey available on the Medicare population. Among the findings:

    • In 2020, health care spending for non-fatal falls among older adults was $80 billion.
    • Medicare paid $53.3 billion of the $80 billion, followed by $23.2 billion paid by private insurance or patients and $3.5 billion by Medicaid.

    “The burden of falls on healthcare systems and healthcare spending will continue to rise if the risk of falls among the aging population is not properly addressed,” the authors write. “Many older adult falls can be prevented by addressing modifiable fall risk factors, including health and functional characteristics.”

    Cost of Emergency Department and Inpatient Visits for Fall Injuries in Older Adults Lisa Reider, et al. Injury, February 2024.

    Summary: The researchers analyzed data from the 2016-2018 National Inpatient Sample and National Emergency Department Sample, which are large, publicly available patient databases in the U.S. that include all insurance payers such as Medicare and private insurance. Among the findings:

    • During 2016-2018, more than 920,000 older adults were admitted to the hospital and 2.3 million visited the emergency department due to falls. The combined annual cost was $19.2 billion.
    • More than half of hospital admissions were due to bone fractures. About 14% of these admissions were due to multiple fractures and cost $2.5 billion.

    “The $20 billion in annual acute treatment costs attributed to fall injury indicate an urgent need to implement evidence-based fall prevention interventions and underscores the importance of newly launched [emergency department]-based fall prevention efforts and investments in geriatric emergency departments,” the authors write.

    Hip Fracture-Related Emergency Department Visits, Hospitalizations and Deaths by Mechanism of Injury Among Adults Aged 65 and Older, United States 2019
    Briana L. Moreland, Jaswinder K. Legha, Karen E. Thomas and Elizabeth R. Burns. Journal of Aging and Health, June 2024.

    Summary: The researchers calculated hip fracture-related U.S. emergency department visits, hospitalizations and deaths among older adults, using data from the Healthcare Cost and Utilization Project and the National Vital Statistics System. Among the findings:

    • In 2019, there were 318,797 emergency department visits, 290,130 hospitalizations and 7,731 deaths related to hip fractures among older adults.
    • Nearly 88% of emergency department visits and hospitalizations and 83% of deaths related to hip fractures were caused by falls.
    • These rates were highest among those living in rural areas and among adults 85 and older. More specifically, among adults 85 and older, the rate of hip fracture-related emergency department visits was nine times higher than among adults between 65 and 74 years old.

    “Falls are common among older adults, but many are preventable,” the authors write. “Primary care providers can prevent falls among their older patients by screening for fall risk annually or after a fall, assessing modifiable risk factors such as strength and balance issues, and offering evidence-based interventions to reduce older adults’ risk of falls.”

    Fall prevention

    Several factors, including exercising, managing medication, checking vision and making homes safer can help prevent falls among older adults.

    “Exercise is one of the best interventions we know of to prevent falls,” Vincenzo says. But “walking in and of itself will not help people to prevent falls and may even increase their risk of falling if they are at high risk of falls.”

    The National Council on Aging also has a list of evidence-based fall prevention programs, including activities and exercises that are shown to be effective.

    The National Institute on Aging has a room-by-room guide on preventing falls at home. Some examples include installing grab bars near toilets and on the inside and outside of the tub and shower, sitting down while preparing food to prevent fatigue, and keeping electrical cords near walls and away from walking paths.

    There are also national and international initiatives to help prevent falls.

    Stopping Elderly Accidents, Deaths and Injuries, or STEADI, is an initiative by the CDC’s Injury Center to help health care providers who treat older adults. It helps providers screen patients for fall risk, assess their fall risk factors and reduce their risk by using strategies that research has shown to be effective. STEADI’s guidelines are in line with the American and British Geriatric Societies’ Clinical Practice Guidelines for fall prevention.

    “We’re making some iterations right now to STEADI that will come out in the next couple of years based on the World Falls Guidelines, as well as based on clinical providers’ feedback on how to make [STEADI] more feasible,” Vincenzo says.

    The World Falls Guidelines is an international initiative to prevent falls in older adults. The guidelines are the result of the work of 14 international experts who came together in 2019 to consider whether new guidelines on fall prevention were needed. The task force then brought together 96 experts from 39 countries across five continents to create the guidelines.

    The CDC’s STEADI initiative has a screening questionnaire for consumers to check their risk of falls, as does the National Council on Aging.

    On the policy side, U.S. Rep. Carol Miller, R-W.V., and Melanie Stansbury, D-N.M., introduced the Stopping Addiction and Falls for the Elderly (SAFE) Act in March 2024. The bill would allow occupational and physical therapists to assess fall risks in older adults as part of the Medicare Annual Wellness Benefit. The bill was sent to the House Subcommittee on Health in the same month.

    Meanwhile, older adults’ attitudes toward falls and fall prevention are also pivotal. For many, coming to terms with being at risk of falls and making changes such as using a cane, installing railings at home or changing medications isn’t easy for all older adults, studies show.

    “Fall is a four-letter F-word in a way to older adults,” says Vincenzo, who started her career as a physical therapist. “It makes them feel ‘old.’ So, it’s a challenge on multiple fronts: U.S. health care infrastructure, clinical and community resources and facilitating health behavior change.”

    Related research

    Environmental Interventions for Preventing Falls in Older People Living in the Community
    Lindy Clemson, et al. Cochrane Database of Systematic Reviews, March 2023.

    Summary: This review includes 22 studies from 10 countries involving a total of 8,463 older adults who live in the community, which includes their own home, a retirement facility or an assisted living facility, but not a hospital or nursing home. Among the findings:

    • Removing fall hazards at home reduced the number of falls by 38% among older adults at a high risk of having a fall, including those who have had a fall in the past year, have been hospitalized or need support with daily activities. Examples of fall hazards at home include a stairway without railings, a slippery pathway or poor lighting.
    • It’s unclear whether checking prescriptions for eyeglasses, wearing special footwear or installing bed alarm systems reduces the rate of falls.
    • It’s also not clear whether educating older adults about fall risks reduces their fall risk.

    The Influence of Older Adults’ Beliefs and Attitudes on Adopting Fall Prevention Behaviors
    Judy A. Stevens, David A. Sleet and Laurence Z. Rubenstein. American Journal of Lifestyle Medicine. January 2017.

    Summary: Persuading older adults to adopt interventions that reduce their fall risk is challenging. Their attitudes and beliefs about falls play a large role in how well they accept and adopt fall prevention strategies, the authors write. Among the common attitudes and beliefs:

    • Many older adults believe that falls “just happen,” are a normal result of aging or are simply due to bad luck.
    • Many don’t acknowledge or recognize their fall risk.
    • For many, falls are considered to be relevant only for frail or very old people.
    • Many believe that their home environment or daily activities can be a risk for fall, but do not consider biological factors such as dizziness or muscle weakness.
    • For many, fall prevention simply consists of “being careful” or holding on to things when moving about the house.

    “To reduce falls, health care practitioners have to help patients understand and acknowledge their fall risk while emphasizing the positive benefits of fall prevention,” the authors write. “They should offer patients individualized fall prevention interventions as well as provide ongoing support to help patients adopt and maintain fall prevention strategies and behaviors to reduce their fall risk. Implementing prevention programs such as CDC’s STEADI can help providers discuss the importance of falls and fall prevention with their older patients.”

    Reframing Fall Prevention and Risk Management as a Chronic Condition Through the Lens of the Expanded Chronic Care Model: Will Integrating Clinical Care and Public Health Improve Outcomes?
    Jennifer L. Vincenzo, Gwen Bergen, Colleen M. Casey and Elizabeth Eckstrom. The Gerontologist, June 2024.

    Summary: The authors recommend approaching fall prevention from the lens of chronic disease management programs because falls and fall risk are chronic issues for many older adults.

    “Policymakers, health systems, and community partners can consider aligning fall risk management with the [Expanded Chronic Care Model], as has been done for diabetes,” the authors write. “This can help translate high-quality research on the effectiveness of fall prevention interventions into daily practice for older adults to alter the trajectory of older adult falls and fall-related injuries.”

    Disparities

    Older adults face several barriers to reducing their fall risk. Accessing health care services and paying for services such as physical therapy is not feasible for everyone. Some may lack transportation resources to go to and from medical appointments. Social isolation can increase the risk of death from falls. In addition, physicians may not have the time to fit in a fall risk screening while treating older patients for other health concerns.

    Moreover, implementing fall risk screening, assessment and intervention in the current U.S. health care structure remains a challenge, Vincenzo says.

    Related research

    Mortality Due to Falls by County, Age Group, Race, and Ethnicity in the USA, 2000-19: A Systematic Analysis of Health Disparities
    Parkes Kendrick, et al. The Lancet Public Health, August 2024.

    Summary: Researchers analyzed death registration data from the U.S. National Vital Statistics System and population data from the U.S. National Center for Health Statistics to estimate annual fall-related mortality. The data spanned from 2000 to 2019 and includes all age groups. Among the findings:

    • The disparities between racial and ethnic populations varied widely by age group. Deaths from falls among younger adults were highest for the American Indian/Alaska Native population, while among older adults it was highest for the white population.
    • For older adults, deaths from falls were particularly high in the white population within clusters of counties across states including Florida, Minnesota and Wisconsin.
    • One factor that could contribute to higher death rates among white older adults is social isolation, the authors write. “Studies suggest that older Black and Latino adults are more likely to have close social support compared with older white adults, while AIAN and Asian individuals might be more likely to live in multigenerational households,” they write.

    “Among older adults, current prevention techniques might need to be restructured to reduce frailty by implementing early prevention and emphasizing particularly successful interventions. Improving social isolation and evaluating the effectiveness of prevention programs among minoritized populations are also key,” the authors write.

    Demographic Comparisons of Self-Reported Fall Risk Factors Among Older Adults Attending Outpatient Rehabilitation
    Mariana Wingood, et al. Clinical Interventions in Aging, February 2024.

    Summary: Researchers analyzed the electronic health record data of 108,751 older adults attending outpatient rehabilitation within a large U.S. health care system across seven states, between 2018 and 2022. Among the findings:

    • More than 44% of the older adults were at risk of falls; nearly 35% had a history of falls.
    • The most common risk factors for falls were diminished strength, gait and balance.
    • Compared to white older adults, Native American/Alaska Natives had the highest prevalence of fall history (43.8%) and Hispanics had the highest prevalence of falls with injury (56.1%).

    “Findings indicate that rehabilitation providers should perform screenings for these impairments, including incontinence and medication among females, loss of feeling in the feet among males, and all Stay Independent Questionnaire-related fall risk factors among Native American/Alaska Natives, Hispanics, and Blacks,” the authors write.

    Resources and articles

    This article first appeared on The Journalist’s Resource and is republished here under a Creative Commons license.

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