Traumatic Brain Injury

More and more people, especially men, seem to be suffering from Traumatic Brain Injury (TBI). So many write in to say how the NFL has affected them greatly. Road accidents and sporting accidents seem to be the main reason.

A great concern is the costs for long term care. Which are as high as 40 to 50 billion US dollars each year. Every 15 seconds in the USA someone suffers from a traumatic brain injury TBI. More than one and half million people each year suffer, more than 50,000 die. It causes more deaths in men under 35 than all other diseases combined. 80,000 are permanently disabled.

Over the years many substances have been tested, all have failed apart from progesterone treatment. In 2006 the first successful trial was published using progesterone via IV. Over the course of three years, 100 TBI patients were studied. Some were given standard treatment to control bleeding and fevers, together with surgery for head-injury. Others were also given intravenous progesterone, at triple the highest natural levels at the end of pregnancy. Women can produce over 400ng/ml progesterone during the third trimester. This would equate to 1200mg/day progesterone via IV transfusion. This study showed that 71% of the TBI victims were men.

Sadly there is a tremendous amount of confusion regarding progesterone. One popular misguided bit of information is that progesterone is considered a female hormone! It is not a sex hormone, it is not an exclusively female hormone. It plays no part in the secondary sexual characteristics which develop at puberty. This is governed by estrogen and testosterone.

It is secreted primarily by the ovaries in females and the testes in men. Smaller amounts are produced by the adrenal glands, the brain and glial cells. There are no great quantitative differences in production between men and women outside the luteal phase. It is the precursor to the sex hormones testosterone and estrogen, and to cortisol and aldosterone.

Progesterone regulates gene expression, has a positive fundamental effect on cell differentiation and growth, with anti-oxidative and autoimmune anti-inflammatory mechanisms. It positively affects the nervous system by stimulating neurotrophic factors, quenching oxidative hyperactivity and regulating autoimmune responses.

It reduces programmed cell death and the synthesis of inflammatory factors that can kill neurons hours to days after traumatic brain injury. It's an anti-inflammatory and has been shown to reduce the response of natural killer cells as well as other inflammatory cytokines and proteins.

Injections of progesterone given after traumatic brain injury have been shown to improve cognitive, sensory and motor recovery, enhancing both short and long term recovery. Topically applied progesterone is rapidly absorbed transdermally and its patterns of distribution and metabolism are comparable to those reported for intravascular progesterone.

It readily crosses the blood brain barrier reducing oedema to barely measurable levels in traumatic brain injury. It reduces lipid peroxidation and the generation of isoprostanes, which contribute to post-injury ischaemic conditions. Isoprostanes are potent inflammatory compounds and are accurate markers of lipid peroxidation in animal and human models of oxidative stress. It also metabolites decrease pro-apoptotic and increase anti-apoptotic enzymes in TBI. Progesterone also reduces the expression of pro-inflammatory genes and their protein products, and reduces the area of necrotic cell death, plus improving behavioural outcomes in TBI.

Progesterone protects neurons on the far side of the injury which would normally die. It also produces significant sparing of cognitive, sensory and spatial learning performance after TBI. The progesterone metabolite allopregnanolone reduces the brain's response to stress, by potentiating the action of GABA, plus progesterone regulates the secretion of catecholamines during stress.

No adverse side effects have been found in the studies on traumatic brain injury. Unlike estrogen, which can exacerbate brain injury, progesterone can be given to both males and females without affecting gender and sexual functions.

Progesterone promotes regeneration and myelination of axons, and has a neuroprotective and antioxidant effect in the injured nervous system. It has multiple effects on glial cells, it influences growth, differentiation and increases the expression of myelin-specific proteins in oligodendrocytes, and potentiates the formation of new myelin sheaths by Schwann cells in vivo.

The potential for progesterone in various disorders is enormous. Strokes, which affects more than 700,000 Americans each year, with over 150,000 dying, paediatric and geriatric TBI, reducing oedema in cardiac and vascular surgery, MS (multiple sclerosis), spinal cord injuries, motor neuron disease, diabetic neuropathy, peripheral neuropathy, protection against cell excitotoxicity, preventing the deterioration of myelin which occurs in the peripheral nerves during ageing and more.

Sadly and incorrectly, progesterone is often mistaken for synthetic progestins used in contraceptives. Medroxyprogesterone acetate (MPA), better known as Provera, is possibly the most common progestin, also available as an injection or depot, as it's usually referred to. The progesterone molecule is greatly changed in MPA, and it does not have the same metabolic effect. Although it does reduce oedema in TBI, it cannot assist in behavioural recovery. An important aspect of progesterone are it's metabolites, particularly allopregnanolone. This is a potent anti-inflammatory, antioxidant and analgesic.

In 1913, Nobel laureate Santiago Ramon y Cajal wrote, "In the adult brain, nervous pathways are fixed and immutable. Everything may die, nothing may be regenerated." Donald Stein's work of over 40 years has proven him wrong, the brain has an immense capacity to regenerate, given the nutrients it needs.

For example, Vitamin D3 is also neuroprotective. It reduces neuronal loss when used alone in traumatic brain injury studies. But further studies have shown that adding D3 to the progesterone protocol, increased the benefits of progesterone. Vitamin D3 deficiency increases levels of inflammatory cytokines and proteins, which increase substantially when injured. Given the fact that the majority of the world's population is D3 deficient, it's understandable that adding this vital antioxidant would be of added benefit.

Nutrients and Amino Acids which have proven helpful are:

N-Acetyl Cysteine (NAC) has been shown to be neuroprotective in traumatic brain injury. A potent antioxidant, it reduces inflammatory cytokines and proteins, reducing oedema, blood brain barrier permeability, and cell death.

Taurine concentrations drop sharply with severe trauma. Taurine is unique among amino acids as it's not bound in tissue, but serves as an osmolyte with antioxidant properties. One of the most calming of the amino acids, it helps to reduce the stress response.

Glutamine also drops sharply with trauma, it's the preferred fuel for the gut, liver, and immune cells and serves as a precursor for antioxidants. Increasing both taurine and glutamine reduces morbidity.

Arginine is another potent anti-inflammatory, levels drop during accidental or surgical trauma. It aids in wound healing and speeds recovery time after surgery. Assists in glucose metabolism, insulin production and growth hormone. It also detoxes the liver and boosts the immune system.

Glycine repairs skin and connective tissue, energy reserves drop during trauma, having enough glycine increases energy. It's a calming amino acid, thereby lessening the stress response to the trauma.

Tyrosine is essential for any stressful situation, acute, uncontrollable stress depletes tyrosine and thereby dopamine and noradrenaline, leading to depression and a rise in corticosterone, tyrosine reverses this. It's part of the enkephalin peptide involved in regulating and reducing pain.

The B vitamins drop sharply when stressed. B6 in particular is needed to metabolise all the amino acids. B5 is the anti stress vitamin.

Emory University doctors are studying the use of progesterone in treating traumatic brain injuries, like the one suffered by Marc Baskett.

Here Dr. Kellerman also of Emory describes a progesterone treatment for those who have just suffered a traumatic brain injury. View the video.