Over 100 years ago, the founder of osteopathic medicine, Dr. Andrew Taylor Still, MD, had a remarkable insight about disease and the body's ability to get rid of its trash. He observed that when the body's trash removal system -  the lymphatics - was working unimpeded, "we have no substance detained long enough to produce fermentation, disease, sickness, or death." That insight, once dismissed and ignored by medicine, is now being proved correct as researchers have rediscovered the power of the lymphatic system to amplify the body's healing powers.

Nowhere is this "revolution" in the understanding of the key role of the trash removal system more pronounced than in the study of neurological impairments of the brain.  We now know that the brain's lymphatic system - known as the "glymphatic system" -  is critical to the brain's health. One prominent researcher has even stated that "essentially, all neurodegenerative diseases are associated with the accumulation of cellular waste products."  The brain's toxin removal system is impaired after traumatic brain injury. Unless it is repaired and fluid flow restored, inflammation will ravage the brain.  When the system starts to work better, the brain can begin its journey towards healing. 

This research study is fascinating because it explores another aspect of the brain's trash removal system in connection with Alzheimers' dementia. More and more studies are exploring the potent effects of cleaning out the amyloid beta trash that builds  up in the brains of AD patients. In this study, the researchers used ultrasound to provoke immune cells in the brain, known as microglia, to ratchet up their trash removal activities. In 75% of the mice, the re-energized microglia removed enough of the amyloid beta plaque in the brain to result in improved performance in three memory tasks.

If this research is translatable to human beings, it represents a dramatic step in the conquest of this terrible disease and reinforces the principle that cleaning up the trash helps the brain heal. The next step would be to flush those activated immune cells and their trash burden out of the brain entirely. That will be the subject of another scoop! in the near future.

If you keep up on the literature about TBI, one comment you see over and over is: "there are no treatments for TBI" -- other than rest,  and perhaps some drugs for symptomatic relief and some cognitive rehab. They certainly don't believe there is any treatment in the first 24 hours after injury. Except, it turns out, there is.

This is a difficult problem to research. In order to study effective treatments, researchers need access to patients within those first critical hours, a time when most patients are unaware they even have a mild traumatic brain injury. Then the researchers would have to make sure the patients were compliant with the treatment and be able to reassess them at the end of a certain period. Where could researchers find such a group of patients? In the theater of war.

A group of researchers traveled to a field hospital in Iraq to test their hypothesis that NAC (N-acetyl-cysteine), a derivative of the amino acide L-cysteine, could protect the brain against  cognitive, vestibular (balance) and auditory injuries to the brain following  blast exposure. The researchers chose NAC for a number of reasons: it has a 40 year safety record, it has shown strong neuroprotective effects in animal studies, and it has potent anti inflammatory and anti-oxidant properties. And since it doesn't cross the blood brain barrier very easily, it can enter the brain in the places where injury has made the barrier permeable and focus its healing effects there.

In this double-blinded, placebo controlled randomized study, 29 soldiers were given a dose of NAC within 24 hours of sustaining concussions following exposure to  significant ordnance blast. The results at the end of seven day course of treatment were nothing short of astonishing. Of the 29 soldiers who were given NAC and a headache medication within 24 hours of injury, 86% had complete symptom resolution within seven days, as compared to 11% of those receiving placebo treatment. In other words, 86% of the  soldiers receiving NAC and the headache medication had normal cognitive tests at the end of seven days. The researchers have followed this study with another one to confirm their findings. (I will be discussing that shortly as well).

NAC is an emerging superstar in the quest to find safe and effective treatments for MTBI. NAC is safe, well-studied in other contexts, derived from an amino acid contained in our food, and works with a broad spectrum of actions and with multiple systems in the body.  This study and others like it are once again demonstrating that the brain will heal with the right kind of help.

There is an impressive body of literature on the powerful ability of melatonin to protect the brain from injury after trauma, yet there is little published about how it can improve cognitive function. The research in this article, while not dealing specifically with traumatic brain injury, dramatically demonstrates melatonin's brain-protecting action in patients with mild cognitive impairment. Melatonin is most known for its role in our sleep cycle, but it has powerful neurotrophic (neuron-protecting) effects as well.

This was a long term (5 year) study following on the heels of earlier research that reported daily bedtime melatonin significantly improved cognitive function in MCI patients. Since that study was greeted with skepticism, the authors undertook a longer one with more participants. The results were equally as astonishing.

In every parameter tested for cognitive performance, the patients who were treated with melatonin did better. They had better cognitive function, lower rates of depression, and better quality of sleep. They were able to reduce their use of benzodiazepines for sleep (only 6.2% vs. 62.8% for the non-melatonin group) - an important result, since benzodiazepines can cause cognitive impairment by themselves (see my curated subject on sleep-wake disorders and concussion) and actually suppress natural melatonin levels.

We know that traumatic brain injury interferes with melatonin production, and that this loss is correlated with sleep disturbances after TBI.  We also know that melatonin protects the injured hippocampus after tbi, a key center of the brain's  learning and memory functions, and improves spatial memory deficits. Melatonin's ability to shield the brain's critical structures involved with memory and learning may explain its powerful ability to improve cognitive impairments.

To date, there are no FDA-approved treatments for cognitive impairments following TBI. But there is literature on the treatment of cognitive impairment in conditions with similar pathophysiology, such as AD (Alzheimers' Disease). Alzheimers patients have profoundly low melatonin levels, and melatonin can combat the damage caused by amyloid beta and tau proteins which accumulate in the brains of Alzheimers' patients.

Melatonin, while generally safe, cannot be taken by everyone. It is contraindicated if you are already taking prescription sleep medications. It interacts with some diabetes meds, immunosuppressants, blood thinners, blood pressure medicine, birth control pills, and a few other meds. If you are on a prescription drug, it's always wise to get medical advice before you start a melatonin regimen.

Many of my patients report dramatic improvements in cognitive function with bedtime melatonin spray. Hopefully new research is on the horizon that can give us more insight into this miraculous hormone.

Right on the heels of the first study on the healing effects of Granulocyte-Colony Stimulating Factor (G_CSF - see my commentary on that article) comes this study that demonstrated that adding human umbilical stem cells to the mix greatly improved the outcomes.

The previous article demonstrated that G-CSF can stimulate creation of new neurons and improve cognitive outcomes in the injured brain.This study demonstrates that when G-CSF  is combined with umbilical human stem cells (hUBC), a known anti-inflammatory agent, the healing results were even more dramatic and long lasting.

 Brain inflammation, though a necessary and basically healing response to a traumatic brain injury, can spin out of control. When that happens, brain cells  die and their networks become impaired, taking with them our memories, cognitive functions, and motor abilities.

Combining hUBCs and G-CSFs produced more stable and far reaching improvements than either substance alone. Because these natural substances work on many biological levels and with many biological systems - taming inflammation, inducing the growth of new neurons, healing blood vessels, protecting brain cells from dying - using them is a  far better strategy than a drug therapy that targets only a single piece of a vast and complex biological injury.

While this study focused on motor improvements rather than cognitive improvement, it is likely that the combination therapy will have a powerful impact on cognitive improvement as well. The therapy's ability to help inflammation resolve,  induce the growth of new neurons and reduce cell loss in our memory center, the hippocampus, all point to a sustained positive impact on cognitive improvement.

The original article can be found at 

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0090953.