Brain Health and Function

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

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Circulation to the brain and the blood brain barrier

We have evolved an elaborate system of restricting and regulating what is allowed into the brain. Since the brain is the seat of control of the rest of the body, this tissue needs greater protection, and the fluids that circulate to the brain cells and tissues are separated into the cerebrospinal fluid and the blood, with a smart barrier set up between these two in most of the brain. This is called the brain-blood barrier, and generally restricts larger molecules, such as bacteria and proteins, from freely entering the cerebrospinal fluid, or extracellular fluid. This is accomplished by the creation of tight cellular junctions in the vascular membrane, or epithelium. Some areas of the brain do not have a blood brain barrier, though, such as the pineal gland, which freely secretes the important hormone melatonin into the circulation to regulate cellular processes throughout the body, and the pituitary gland, whose posterior portion secretes the hormones oxytocin and ADH into the blood. Areas of the brain bordering the central ventricles, or reservoirs of cerebrospinal fluid, are also free of the brain-blood barrier, and these tissues are important seats of regulation of fluid, metabolites and neurohormones, as well as areas that detect toxins in the blood and initiate responses.

Knowledge of the blood brain barrier (BBB) allows nutrient and herbal experts to create effective medicines that are more sure to reach certain areas of the brain. In the unregulated field of herbal and nutrient medicine, though, the consumer and the physician needs to rely upon the integrity of the professional company that supplies these products to insure effectiveness. Products on the shelf, especially cheaper products, and those that rely on heavy advertising to sell, are often not what they claim to be, or base their products on unreliable science, using the cheapest materials instead of the most effective. There is no penalty in the U.S. when companies claim that their nutrient and herbal medicines will cross the blood brain barrier and actually affect the brain the way they are advertised, and instead do not work as advertised. The fact that many of these products are now produced by the pharmaceutical industry, which loses money when nutrient and herbal products effectively compete with their more expensive synthetic drugs, leads many Complementary Medicine physicians and patients to view many of the commercial products with skepticism.

Important nutrients that are able to cross the blood-brain barrier include L-Glutamine, 5HTP, Acetyl L-Carnitine, Phosphotidyl serine, DHA omega-3 essential fatty acid (docosahexaenoic acid), CoQ10, 7-keto DHEA (dehydroepiandosterone), and DMAE (dimethylaminoethanol). Important and often used herbs for brain health and function that contain active chemical metabolites that may easily cross the blood-brain barrier include Gingko biloba, Vinpocetine, Huperzine A, and Bacopa monniera, but many herbal active metabolites may cross the brain-blood barrier. These all will be described later in this article. When devising strategies to promote brain function and health, though, these are the important nutrient and herbal medicines to consider.

On the other side of the blood brain barrier is the cerebrospinal fluid. The cerebrospinal fluid (CSF) is a store of essential nutrients in the brain, brainstem and spinal cord. The main functions of CSF are to protect the brain from trauma, supply nutrients to CNS tissues and cells, and remove waste products of cerebral metabolism to the veinous system. CSF is composed of electrolytes (mostly sodium, but also potassium, magnesium, calcium), much glucose, urea and uric acid, creatinine, and a small amount of protein and protein peptides. The protein concentration of CSF is dramatically lower than that of blood plasma, because of the blood brain barrier, and the concentration of immune cells is also very low, unless there is a CSF infection (e.g. meningitis). Lymphocytes normally account for 60-100% of these immune cells in CSF, and these white blood cells consist of the small T cells and B cells more often than the large NK cells (natural killer). Other types of lymphocytes include T helper cells (Th1 and Th2), which are often involved in chronic inflammatory diseases. Analysis of the CSF for abnormal content is now becoming a more important diagnostic tool, especially in diagnosing early Alzheimer's and cognitive dysfunction. The level of amyloid beta protein peptide (A-beta) may be an important marker for the development of Alzheimer's plaque in the brain.

When the integrity of the blood brain barrier is affected, neurological problems may occur. The integrity of the blood brain barrier may be altered by methamphetamines and cocaine, other pharmaceutical drugs, inflammatory cytokines, and environmental toxins. This barrier may also be affected by cardiovascular problems, and disruption of the blood brain barrier is also seen with diabetes and Metabolic Syndrome. The permeability of the brain-blood barrier may be altered by these factors in various ways, allowing a variety of toxins, pathogens, and large molecules to cross. Loss of blood-brain barrier integrity has been recognized as a major cause of profound brain alterations. Studies have shown that regular exercise and various antioxidants reverse this loss of blood-brain barrier integrity induced by methamphetamines, and we can surmise that most problems with the blood brain barrier will be helped by an improved lifestyle and diet. This is a starting point for brain health and functionality. A large number of factors may affect the brain-blood barrier integrity, though, and studies have shown that increased permeability of this barrier is a characteristic of neurodegenerative diseases such as Alzheimer's and Parkinson's, and lies at the heart of mild cognitive dysfunction, as well as a host of problems in the brain. Complementary Medicine offers a variety of treatment protocols to help improve or correct problems with this important regulatory barrier.

A key aspect of study of the blood brain barrier and cognitive dysfunction is the regulation of transport of neurotoxic metabolites such as beta-amyloid peptide, a fatty protein fragment that accumulates in the brain and slowly deteriorates brain function. P-glycoprotein (Pgp), or permeability glycoprotein, is a membrane transporter expressed in the blood brain barrier, the intestinal epithelium, liver cells, and kidney cells. P-glycoprotein has been found to regulate the amount of beta-amyloid protein, or so-called "sticky protein", that is allowed through the blood brain barrier, which leads to various neurodegenerative pathologies, such as Alzheimer's disease. Pgp, also called ABCB1, is a membrane transporter for an array of substances, though, including peptides, lipids, and many pharmaceuticals, including digoxin, immunosuppressive agents, glucocorticoids (such as prednisone and desmethasone), and steroids, as well as xenobiotics (organic toxins), and some naturally derived drugs, such as colchicine, quinidine, and tacrolimus. New drugs designed to inhibit Pgp may thus be problematic. A better tactic is being researched, normalizing the homeostatic mechanisms of Pgp and other membrane transport proteins to properly regulate transport across the blood brain barrier of beta-amyloid peptides. Current Alzheimer research has focused on the role of advanced glycation endproducts (AGEs) and the receptors for these glycoproteins (RAGEs), as a means to affect the blood brain barrier to prevent the building blocks of cognitive dysfunction and Alzheimer's disease.

Although the many possible mechanisms of neurodegeneration have made this area of medicine confusing, not only for the patient, but for the physician and researcher as well, promising research has identified a host of pathological problems that may lead to cerebrovascular dysfunction involving the blood brain barrier, and contribute to the cognitive decline and dementia in these diseases. These problems may precede the beta-amyloid accumulation of neurotoxin in Alzheimer's disease. Besides P-glycoprotein, two membrane receptors are found to regulate amyloid-beta peptide transport across the blood brain barrier. These are the low density lipoprotein receptor related protein 1 (LRP1), and the receptor for advanced glycation endproducts (RAGE). The P-glycoprotein (Pgp) and LRP1 membrane transporters regulate the efflux, or clearing, of amyloid beta peptide, while the RAGEs regulate the influx. The neurovascular hypothesis of the origins of neurodegeneration implicates excess expression of RAGE due to excess circulating AGEs, deregulated LRP1, aberrant angiogenesis, and arterial inflammation, as the main factors in this blood brain barrier dysfunction. A set of therapeutic protocols is suggested to reduce neuroinflammation, enhance amyloid-beta clearance and neurovascular repair, and improve blood flow in the brain (see the research link cited below in additional information from the University of Rochester in New York).

LRP1 is a protein receptor in the blood brain barrier cell membrane involved in endocytosis and transfer of the various molecules described above. LRP1 interacts with Apolipoprotein E (apoE4) to import cholesterol into the brain. Dysfunction of this process is also thought to be a factor in neurodegenerative cognitive dysfunction by decreasing cholesterol in the brain and damaging neural function by inhibiting myelin sheaths and support cells responsible for neurotransmission, as well as inhibiting neural growth. LRP1 also interacts with inflammatory kinases (MAPK), calcitonin receptors (regulation of calcium), and thrombospondin 1 (affecting angiogenesis and platelet aggregation). Apolipoprotein E is also now heavily studied for its relation to the pathogenesis of Alzheimer's disease, cognitive dysfunction, atherosclerosis, and immunoregulation. Chronic inflammation may play a part in dysfunctions related to Apolipoprotein E (APOE). APOE is also produced by the support cells in the brain, and neurons express APOE receptors. Restoration of a healthy homeostasis of lipids, inflammation, angiogenesis, clotting factors, calcium, and cholesterol may all play a part in normalizing LRP1 homeostasis to improve clearing of amyloid beta peptide from the brain. A holistic treatment protocol is warranted, rather than a specific allopathic chemical.

To affect these healthy protocols, nutrient and herbal formulas to block the production and accumulation of advanced glycation endproducts (AGEs) and to inhibit angiogenesis (e.g. IP6), may be combined with herbal formulas to reduce chronic neurovascular inflammation (e.g. from TNF-alpha), and improve cerebrovascular circulation and oxidant clearance. Of course, improved diet and exercise routines, and acupuncture, may be combined with this strategy to improve neurovascular health, the blood brain barrier, and prevent the slow progression of neurodegenerative disease and cognitive dysfunction. More specific research has identified a host of herbal and nutrient chemicals that contribute to this healthy treatment protocol as well. For instance, in 2000, researchers at the famed University Hospital Zurich, in Switzerland, showed that Hypericum perforatum (St. John's Wort) increased P-glycoprotein expression, perhaps facilitating the transport of other beneficial chemicals in herbs and nutrient medicines to the brain. Piperine, or Kava, was shown to enhance bioavailability of certain chemicals, such as phenytoin via the P-glycoprotein modulation. Certain natural flavonols, such as quercetin, kaempferol, and galangin are found to be potent stimulators of PgP-mediated efflux. While these studies explored the mechanisms by which high doses of the herbs could alter the efflux of certain medications in the intestinal membrane, these same studies show that these commonly used herbs may facilitate the transport metabolism at the blood brain barrier. Resveratrol, an active chemical in the herb Polygonum cuspidatum, or Hu zhang, is shown to modulate the blood brain barrier to protect the brain from toxicity (PMID: 25448605). While such research is not simple to apply directly, it does add to the potential to utilize herbal and nutrient medicine in more complex protocols by knowledgeable physicians.

Circulation in the Brain past the Blood Brain Barrier and White Matter Disease

Circulation in the brain is more tightly regulated than in the rest of the body. Both the blood circulation and the cerebrospinal fluid circulation are important, and as stated, these are separated in most areas of the brain by a tight blood-brain barrier that restricts free flow of larger molecules and charged ions. Blood flow to the brain is more vital than to other parts of the body. When blood flow is interrupted, restricted, or excessive, dysfunction occurs, and the ill effects may range from poor cognitive function, dizziness, and headache, to the paralysis and loss of speech seen in strokes. Fortunately, there are elaborate systems to preserve a constant flow and pressure in the blood vessels of the brain. When blood pressure rises, the blood vessels automatically contract with stretch, and through all normal ranges of arterial blood pressure, which greatly exceed those we deem as indicative of chronic hypertension, blood flow will remain constant. Very high, or malignant, blood pressure, though, may result in damage to the arterial linings and to the blood-brain barrier. Patients subjected to very high periods of blood pressure need to treat this arterial lining, or epithelium, to effect better repair. Patients with chronic hypertension, while not damaging the brain arterial lining and blood-brain barrier, do create a situation over time of adaptation, and it is shown that with these patients that what we consider a normal blood pressure, as well as periods of low blood pressure, may result in tissue ischemia in the brain, or poor oxygenation. Often, the patient that had a moderate hyptertension for years, and now takes a number of hypertension drugs, may have a low to normal blood pressure, and be subject to periods of tissue ischemia, with lowered oxygen supply to areas of the brain now causing poor function. Maintenance of the blood vessels is thus very important, as well as maintaining health and function of the brain tissues and cells, even when taking these blood pressure medications.

A number of chemicals in circulation may affect the blood vessels and circulation in the brain as well. Carbon dioxide, acidity (low pH), nitric oxide, and adenosine are the chief compounds that may stimulate dilation of the blood vessels. These chemicals may be beneficial, released from brain cells and tissues in areas of the brain with increased activity and need for more oxygen and nutrients in the blood, or may be harmful, released into circulation due to inflammatory mechanisms, poor control of acidity in the body, poor function of the mitochondria, or excess oxidative stress. When these conditions become chronic, the normal regulatory responses to these chemicals may be altered, adversely affecting the ability of the body to respond to increased need for oxygen and nutrients. Using drugs to inhibit mechanisms of inflammatory mediators, stomach acid production, etc., may decrease pesky symptoms, but will not address the underlying problems that add to poor brain function and health. Acidity and chronic inflammation are two key areas that need to be addressed. Chronic acidity in the body cannot be fully measured, only local acidity in the blood, urine and saliva, and the body's chief reaction to acidity is buffering with increased circulating carbon dioxide (pCO2) and/or calcium. Calcification of tissues may then occur, also inhibiting the circulatory capability in the body with hardened arteries. These issues become very important to brain health and function, especially in aging, and in patients with chronic problems with inflammation, poor gastric function, hormonal deficiencies, and oxidative stress.

One of the most widely studied herbs in the world is Gingko biloba, and consequently it is now the most widely prescribed and best selling herbal medication in Europe. Of the more than 40 active ingredients in this herb, the flavonoids and terpenoids are believed to exert most of the studied medicinal effects. Both flavonoids and terpenoids have potent antioxidant properties, but the flavonoids are thought to be more neuroprotective and beneficial to arterial health, while the terpenoids are thought to improve blood flow by reducing the platelet aggregation and dilating the blood vessels. Gingko biloba extracts, especially a standardized tincture extract, have been proven to exert benefits to memory and cognitive dysfunction in Alzeimer's patients, and slow the progression of cognitive dysfunction that precedes dementia. Numerous studies cite the benefits in early stages of neurodegenerative cognitive dysfunction, but like most medications, show little benefit in later stages of dementia. Gingko biloba has also been proven to aid other vascular circulatory disorders, such as intermittent claudication and macular degeneration. Other neurodegenerative disorders, such as glaucoma, have also found proven benefit from Gingko extract. Using a professional quality standardized extract as a base in formulas of tinctured herbal extract is recommended to treat circulation and oxidative stress in the brain.

Gingko biloba by itself is not the answer to correcting problems related to circulation and oxidant stress in the brain, though, and an array of professionally prescribed herbs and nutrient medicines should be considered in the overall protocol. Acupuncture stimulation acts synergistically with these herbal and nutrient protocols to complete the restorative treatment. Some of these more well studied herbs and nutrient medicines will be explained later in this article and in Additional Inforamtion. These herbs and nutrient medicines may be combined in a package of care that includes short courses of acupuncture, nutrient medicine, advice with diet and lifestyle, and even deep tissue physiotherapies, which provide proven benefits to immune and hormonal balance, and decrease of inflammatory stress.

White Matter Disease (WMD), or small vessel atherosclerotic disease of the brain, is now found to be very prevalent in the population due to the introduction of advanced imaging technologies. In 2014, experts around the world, such as the British Psychological Society, acknowledged that WMD is responsible for up to a fifth of all strokes worldwide and a major contributing factor in up to 45 percent of all dementias, such as Alzheimer's diseases and parkinsonism, as well as a large number of undiagnosed slowly progressive syndromes of cognitive impairment. The problem involves small vessel hardening and progressive decrease in vital blood nutrients to white matter in the brain, which is mainly the myelinated fibers and support glia to the neurons. Vascular cognitive impairment is the primary manifestation, usually undiagnosed, as it progresses slowly and insidiously, but an array of health problems may be caused or worsened by WMD, depending on the area of the brain affected. Obviously, such a problem demands a more holistic integrated treatment regimen, and there is currently no effective protocol in standard medicine. Low-grade and chronic inflammatory conditions are linked to White Matter Disease, and inflamed white matter is implicated in Multiple Sclerosis, cerebral palsy, and a host of other diseases that are still poorly understood. Simply taking high blood pressure and statin drugs to decrease risk of WMD progression is obviously not addressing the big picture.