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This article was first published on June 13, 2016 at JOURNAL OF MASSAGE SCIENCE
American football is a huge part of American life. It is impossible to imagine our country without the Super Bowl. However, football has also a very dark side associated with death and irreversible changes in the brain function of players.
Let’s look at the life of an average football player. From a relatively young age he undergoes body and head collisions of different intensity. One of the most dangerous consequences occurs during high school and college years when the brain is still going through the final stages of development and at the same time is actively loaded with information.
During these years young athletes frequently experience so called Repetitive Head Injury Syndrome (RHIS). In these cases the young athlete continues to compete after what initially seems like relatively mild head trauma. While doing so he encounters repetitive mild concussions which add up to and create a slowly lingering clinical picture of RHIS.
As it was shown by Boden et al, (2007) 39% (!) of high school football players continued to play during the same season while still having residual symptoms of recent concussions. Later these students who in reality suffer from RHIS are diagnosed with attention deficit disorders or tagged as “academically incapable.”
“The effect of multiple concussions over time remains significant and can result in long-term neurologic and functional deficits. These multiple brain insults are termed Repetitive Head Injury Syndrome” (Cifu, et al., 2014).
While the professional football player continues his career, the intensity and violence of his head injuries increases. Let me give you one stunning example. Scientists from Boston University examined 79 brains of deceased NFL players from Brain Bank and found that 76 (!) had exhibited changes associated with Chronic Traumatic Encephalopathy (Breslow, 2014). These brains were donated by relatives or arranged to be donated by players before they died.
Boxing and Ultimate Fighting are even more gravely dangerous to athletes while less alarming but still hazardous situations happen in ice hockey, soccer and other contact sports.
Finally, we are forever in debt to our veterans who come back home after being severely injured by improvised explosive devices (IEDs) in Afghanistan and Iraq. It was reported that 20% (!) or 233,000 service members who served in Iraq and Afghanistan suffer from Traumatic Brain Injury (Meyer et al, 2010).
For further discussion, the understanding of the mechanism of concussions and its impact on the human brain need to be clarified. When we are running, jumping or even walking, neuronal and axonal membranes are stretched within the normal physiological range. A significant blow to the head can produce sudden sprain of neuronal and axonal membranes and a bouncing impact of the brain against the skull.
We can split events after severe concussion or RHIS into three stages:
1. Hypermetabolism Stage
The stress of brain membranes and micro bleedings into the brain tissue triggers release of different neurotransmitters, especially glutamine, and substances called cytokines which accompany any type of inflammation in our body.
The next step is post-traumatic cellular derangement and an increase in cerebral spinal fluid (CSF) secretion. The first outcome of these events is the increase of intracranial pressure, which compromises cerebral circulation. As it was shown by Yamakami and McIntosh (1989), cerebral circulation can be reduced by up to 50% of normal.
Another equally important event at the early stages after concussion is a dramatic increase of brain metabolism which requires extra glucose to support it (Giza and Hovda, 2001). However, decreased cerebral circulation is unable to deliver the necessary amount of glucose into the brain cells to use it as a fuel. Thus there is a mismatch between glucose demand by the injured brain and its availability, which triggers as McKee and Daneshvar (2015) called it, an “energy crisis in the brain.”
2. Hypometabolism Stage
In approximately 2 to 4 weeks after concussion the brain metabolism slows dramatically because of the negative impact of local inflammation in combination with lack of proper oxygenation (Bergsneider and Hovda, 2000).
At this point ATP or fuel production greatly diminishes by mitochondria. As soon as the normal amount of ATP diminishes, it becomes the first step to the irreversible changes in neural connectivity, especially if the individual continues to suffer repetitive concussions disintegration.
3. Post-Concussion Encephalopathy
If the patient has experienced repetitive mild concussions, he or she starts to develop Post-Concussion Encephalopathy (movement disorders, memory loss, psychiatric behavioral disorders, chronic headaches etc.). One of the major mechanisms of these profound changes in the function of the brain is alternation in the function of so-called tau-protein.
Tau-protein is an important part of normal brain function since it supports the function of neurons. This protein forms microtubules which support neurons with transport of necessary proteins, nutrients and ATP molecules along neuron and transport back waste products. Without that the neuron would deteriorate (Ballatorre et al, 2007).
As a result of concussion, especially RHIS, the normal microtubules deteriorate, tau protein accumulates excessive phosphorus and crumps together and eventually detaches from neurons. Then, these wondering tau proteins accumulate in the different parts of the brain tissue disrupting its normal electrical activity and causing all neurological symptoms associated with RHIS (Gerson et al., 2016). By the way, the same mechanism is responsible for the progression of Alzheimer’s disease.
GLYMPHATIC SYSTEM
Separately I would like to address the Glymphatic System, which is very important for this article and for post-concussion patients. Since the presence of lymphatic vessels wasn’t detected in the brain, the exact mechanisms of waste removal from CNS until recently were a great puzzle for scientists. However, thanks to the works of brilliant Danish neuroscientist Dr. M. Nedergaard we know now how it works. Dr. Nedergaard named the brain’s main waste removal system the Glymphatic System.
While arteries, which bring blood, enter the brain they also pull along CSF which flows along the arteries in a so-called para-arterial influx route located in para-arterial space. Under the pressure generated by arterial pulsation, CSF leaves para-arterial space and forms the connective flow which now goes through the brain tissue itself (i.e., brain parenchyma) and it cleans the waste produced by neurons.
Eventually, the connective flow ends up around the neighboring veins in the para-venous spaces which allow the CSF, which now carries waste products, to be drained along the veins via so called para-venous efflux until CSF with all the waste it carries enters the lymphatic system outside of the brain in the head and neck areas. Thus the flow of CSF itself is a major waste removal mechanism the brain uses to allow neurons to function properly.
However, Dr. Nedergaard didn’t stop there. Recently with a group of colleagues (Xiu et al., 2013) she discovered another critical piece of information. According to a recent study more than 60% of waste formed during normal CNS activity and neuro toxic waste which formed additionally as a result of post-traumatic encephalopathy or Alzheimer’s Disease drains during the sleep! As the authors concluded:
“The restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.” (Xie, et al., 2013).
Finally, there is another recent breakthrough in the work of Louvain et al. (2015) who proved that the drainage to the lymphatic system doesn’t happen only outside of the CNS, but also inside the brain itself. These scientists for the first time detected the presence of the lymphatic vessels inside the brain and in such cases, besides indirect flow of waste products through the Glymphatic System, we now know that the brain can drain waste directly into the lymphatic system inside the CNS.
The information about the Glymphatic System is critically important to massage therapists and to the protocol we will discuss in Part II of this article. It scientifically justifies the critical role Medical Massage plays in the treatment of post-concussion symptoms.
APOPTOSIS
There are a lot of pathological events in cases of RHIS which affect the function of the brain and the brain tries to coupe with them to the best of its ability. One of these mechanisms relative to the Medical Massage practitioner is called apoptosis (AP). AP or death of the cells is executed by the body itself in a programmed fashion. In other words, this protective mechanism allows some cells to die in order to avoid further massive damage. This programmed death is slow disintegration of the cell.
After the cell gets a signal to deteriorate its inner skeleton (or cytoskeleton), it starts to disintegrate and cells develop areas of blebbing and condensation of the nucleus. Finally the cells burst into pieces to form apoptotic bodies which are later cleaned by phagocytes during phagocytosis.
The only way to prevent AP and help neurons survive is to increase cerebral circulation and decrease pressure of CSF.
As readers will see in the Part II of this article the information we discussed above has direct impact on what the massage therapist must or shouldn’t do while working on patients after concussion or post-traumatic encephalopathy. In the final part of the article we will go over the MEDICAL MASSAGE PROTOCOL which must be part of rehabilitation therapy.
The mainstream approach to the treatment of mild to moderate concussion is “rest and time.” Water pills, pain medication and muscle relaxants are some additional tools. Partially this is true – with time and rest the immediate concussion symptoms go away.
The symptoms like disorientation, dizziness, nausea, sleep disorders and headaches will significantly decrease in intensity during the first 15 to 30 days after a concussion. But nobody can predict to what degree the patient will completely recover and if symptoms of post-traumatic encephalopathy might develop, especially if concussions are recurrent.
Thus, it is crucially important to assist the patient to completely recover from all possible directions, especially in the early stages after concussion. At the moment doctors give the green light, Medical Massage must be included into the rehabilitation. The sooner the therapy is implemented the quicker and fuller the recovery the patient will have.
Historically, the MEDICAL MASSAGE PROTOCOL for post-concussion originated in a tragic accident. In 1963 the famous Soviet boxer and two-time Olympic champion, Valeri Popenchenko, collapsed 24 hours after winning the Soviet Union championship. He was diagnosed with severe concussion after the fight he just won.
At that time, the “rest and time” cure was widely implemented. So Valeri was prescribed a three week rest and the immediate post-concussion symptoms indeed disappeared. However, a couple of months after the accident Valeri noticed that he couldn’t focus and every time he tried to exercise he felt very uncomfortable symptoms of palpitation, sweating and light nausea. In other words he developed the so called “exercise intolerance,” which in his case meant the end of his boxing career.
At that time his physician was Professor Dembo, who was also a Soviet authority in sports medicine and massage therapy. Professor Dembo started to dig deeper. He assembled a team of colleagues and his graduate students. This group discovered that the first diagnostic biomarkers to the future development of posttraumatic encephalopathy were irregularities in the function of the autonomic nervous system. These irregularities included: constant fatigue, fluctuation in blood pressure, irregular heart rate, feelings of upset stomach, increased sweat production, etc. If after the disappearance of immediate concussion symptoms these symptoms remain, it is almost a 100% chance that the patient will later develop encephalopathy of a different degree.
As soon as Professor Dembo realized this correlation, he stopped Valeri’s training and started various Medical Massage techniques trying to find the ideal combination of tools to use to activate the sensory receptors in the soft tissues as a tool to restore balance in the autonomic nervous system and help Valeri recover.
Within the following six months Dembo’s team developed the entire treatment protocol for a post-concussion rehabilitation and Valeri’s condition improved tremendously. His focus was restored, he restarted his training and eventually came back to both boxing and later his own scientific career.
Here is the protocol for post-concussion rehabilitation and the rules for its application. The selection of tools and techniques for MEDICAL MASSAGE PROTOCOL depends on the amount of time after the concussion.
HYPERMETABOLISM STAGE (2-3 weeks)
Immediately after concussion the major goal of the therapy is to increase the CSF movement through the glymphatic system and its drainage into the lymphatic system. Thus the treatment protocol is a combination of lymph drainage techniques and cerebral spinal fluid drainage techniques. These first two steps can be applied immediately after head trauma.
Successful drainage of excessive CSF decreases the intracranial pressure with a following lessening of clinical symptoms such as nausea, headaches, blurred vision, etc. An equally important outcome of Medical Massage therapy for these patients is restoration of cerebral perfusion, which in turn prevents development of degenerative changes associated with post-traumatic encephalopathy.
Attention: under normal circumstances any steps of the protocol described below shouldn’t trigger any uncomfortable reactions. However, for post-concussion patients, especially after recent trauma, some steps may trigger unpleasant autonomic reactions as increased head pressure, headache, nausea etc. If patients report any similar problems immediately decrease the intensity of therapy or cease this particular step altogether until the patient can tolerate it. Observe and use your clinical judgment.
Step 1. Repetitive Pumping-Tractions
Lift the client’s head carefully with the right hand and grab the neck with the left hand so that four fingers are on one side of the neck and the thumb on its other side. Then while continuing to hold the neck with the left hand, place the ulnar part of the right hand on the forehead along the frontal sinuses.
Once the hands are in position, ask the client about exhalation and apply slow repetitive pumping-like tractions along the axis of the spine. During the pumping tractions the left hand simultaneously applies repetitive neck compressions with the same frequency. Also during each traction the right hand is directing traction backward from the area of the frontal sinus toward the top of the head. The right and left hands could be switched depending on the therapist’s preference.
Step 2. Repetitive Compressions on the Head and Face
The compression has to be applied with gradually increased pressure to the first threshold of any discomfort. Sustain this pressure on each point for approximately 15 seconds. Pressure should be combined with light manual vibration. Repeat 15 seconds of compression on all proposed areas for the next 10 minutes.
Step 3. Head Compressions
It was suggested to me by Dr. Ross Turchaninov to additionally stimulate the glymphatic system with very gentle, bi-manual repetitive compressions of the skull using soft parts of both palms. The hands are placed on the opposite sides of the head and it gently compresses 3-4 times during the client’s long, slow exhalation. On numerous occasions I have incorporated this proposed technique into original Prof. Dembo’s protocol and it contributed to faster recovery.
Step 4. Pumping Compression on Lateral Neck
The client is positioned on the side. Adjust a towel /pillow so that the neck is well supported and leveled in a horizontal position. Place the ulnar edge of the palm closer to C1. Place four fingers of the other hand in a half grip so the fingertips are aligned in a chain. Place both hands perpendicular to the neck, next to each other. Avoid shaking, especially during the first five treatments.
Using both hands at the same time, apply careful pumping strokes on the lateral neck. Use light pressure and be sure that each stroke has a slightly circular motion. Re-apply similar strokes along the entire lateral neck for one and a half minutes. If the patient can tolerate it, gradually increase pressure. Turn the client’s head to the other side and apply the same therapy on the opposite side of the neck.
Step 1. Thoracic Pump Technique
Frequently even after moderate concussion the client may feel nausea and dizziness during deep inhalation/exhalations. However, usage of the client’s active inhalation is an important tool to accelerate lymph drainage and eventually CSF drainage. This is why Thoracic Pump Technique is such an important treatment tool.
During each inhalation, the diaphragm contacts and descends while additionally decreasing intra-pleural pressure. The drop in the intra-pleural pressure helps to stream air into the lungs but it also is the main driving force for lymphatic circulation. It pulls lymph through the lymphatic system, while it is cleaned in the lymphatic nodes, all the way through until clean lymph is returned into venous circulation. As we discussed in the Part I of this article, the emptied lymphatic system on the head and neck in turn allows the CSF to be drained from the brain.
The client lies on his/her back. Place your hands against the sternum. Ask your client to inhale and exhale. At the time of inhalation, gently resist the expansion of the rib cage applying pressure which the client should overcome while expanding his/her thoracic cage during inhalation. Release the pressure at the end of exhalation and follow the rib cage until it completely collapses before new inhalation efforts. Repeat resistance to the thoracic cage expansion 5 times.
Even gentle resistance of thoracic cage expansion demands stronger contraction of the diaphragm which additionally lowers intra-pleural pressure stimulation lymph drainage and eventually CSF movement. Be sure to use Thoracic Pump Technique only after the client allows the therapist to engage active inhalations as a part of the therapy.
Step 2. Supraclavicular Pump Technique on the Left
Ask your client to turn her/his head to the right. Place your hand in the left supraclavicular area in the junction area of the thoracic duct and the brachiocephalic vein. Apply pumping strokes there trying to fit 3-4 strokes in one client’s exhalation. Repeat these techniques for 3 minutes.
Step 3. Supraclavicular Pump Technique on the Right
Ask your client to turn her/his head to the right. Place your hand in the right supraclavicular area in the junction of the right lymphatic duct and the superior vena cava. Apply pumping strokes there trying to fit 3-4 strokes in one client’s exhalation. Repeat these techniques for 3 minutes.
Step 4. Abdominal Pump Technique
Abdominal Pump Technique, the same way as Thoracic Pump Technique, is a very important driving force for entire lymphatic stimulation. The largest lymphatic vessels including the cisterna chyli are located on the level of the navel and application of Abdominal Pump Technique accelerates movement of the lymph into the thoracic duct and it secondarily increases CSF drainage. Make a fist and place it in the area of the navel. During the client’s prolonged exhalation perform gentle 3-4 pumpings with moderate pressure. Repeat Abdominal Pump technique for 3-5 minutes.
The protocol presented above should be implemented during the Hypermetabolism Stage for approximately the first 7-10 sessions with total duration of each session approximately 35-40 minutes.
HYPOMETABOLISM STAGE (after 3 weeks)
The acceleration of CSF’s movement through the glymphatic system and increase of lymph drainage decreases the intracranial pressure and restores the arterial blood supply to the brain and its venous drainage. Thus the success of the first stage of the therapy coincides with the disappearance or significant reduction of the initial symptoms which appeared after concussion.
From this point the treatment enters the second stage which now targets imbalance within the autonomic nervous system triggered by concussion. As I mentioned above this imbalance and its symptoms are a biomarker and one of the contributing factors to the development of post-traumatic encephalopathy.
One of the first outcomes of Postconcussion Encephalopathy is autonomic irregularities. Unfortunately, they greatly interfere with restoration of cerebral circulation and it overall affects brain recovery from acute trauma contributing to the future development of encephalopathy. Thus, for therapists it is extremely important to understand the equal importance of acceleration of cerebral spinal fluid drainage and restoration of balance between sympathetic and parasympathetic divisions of the autonomic nervous system. I believe that such an integrative approach will help deliver quick and stable clinical results.
The simplest and effective method to balance the activity of the sympathetic and parasympathetic divisions of the autonomic nervous system is full body massage applied with special rules and sequence. The fact that massage therapy affects and balances the autonomic nervous system was confirmed by several Western studies (Barr and Taslitz, 1970; Longworth, 1982). The full body massage session to balance the autonomic nervous system can be seen here:
Each session starts with toes and when working on the upper extremities the therapist should concentrate on fingers. This is the first step which affects the autonomic nervous system. Feet and hands are the most distal parts of the body from the centers (brain and heart) and they are at the very end of the capillary network which is greatly affected by the force of gravity. There are scientists who even consider feet and hands as the reflex zones of the entire cardiovascular system (Chernigovsky, 1980). Some massage modalities like Pericardic Massage are based on this fact (Akmedzhanov et al., 1981).
The usual duration of a full body massage session is 45 minutes. The CSF and Lymph drainage techniques should be continued, but their application should be shortened to 15 minutes. Thus, one hour therapy should include initial application of CSF and Lymph Drainage techniques for 15 minutes, followed by the addition of full body massage for 45 minutes.
Professor Dembo detected that irregularities in the function of the autonomic nervous system are biomarkers for the future development of post traumatic encephalopathy and proposed treatment options based on application of massage therapy.
Today, more than fifty years later, researchers have supported his theory with clinical data. Here is a link posted by a research team in Mayo Clinic in Scottsdale, Arizona which came up with the same conclusions as Prof. Dembo in the 1960s. Autonomic Dysfunction and Concussion - Mayo Clinic.
References:
Akmedzhanov, M.Y., Leshchinskaya, N.P., Arkhangelsky, V.V., Guz, S.Y., Afanasieva, M.S., Sokolov, B.A.: Pericardic Massage and Its Adaptive Effect in Rehabilitation Therapy with
Dosed Physical Exersises in Patients Who had Myocardial Infarction. Vopr. Kurortol. Fizioter. Lech. F iz. Kult., 4:21-23,1981.
Barr, J .S., Taslitz, N.: The Influence of Back Massage on Autonomic Functions. Phys. Ther.,
50(12):1679-1691, 1970.
Chernigovsky, V.N.: Interoreceptors. “Medicine”, Moscow, 1980.
Longworth, J.C.D.: Psychophysiological effects of Slow Stroke Massage in Normotensive
Females. Advan. In Nurs. Scien., July: 44-61, 1982.
Boden BP, Tacchetti RL, Cantu RC, Knowles SB, Mueller FO. Catastrophic head injuries in high school and college football players. Am J Sports Med. 2007 Jul. 35(7):1075-81
Mutch WA, Ellis MJ, Graham MR, Wourms V, Raban R, Fisher JA, Mikulis D, Leiter J, Ryner L. Brain MRI CO2 Stress Testing: A Pilot Study in Patients with Concussion PLoS One. 2014 Jul 17;9(7):e102181.
Meyer KS, Marion DW, Coronel H, Jaffee MS. Combat-related traumatic brain injury and its implications to military healthcare. Psychiatr Clin North Am. 2010 Dec. 33(4):783-96.
Giza CC, Hovda DA (2001) The neurometabolic cascade of concussion. J Athl
Train 36: 228–235.
Xie, L., Kang, H., Xu,Q., Chen, M.J., Liao, L., Thiyagarajan, M., O’Donnell, J., Christensen, D.J., Nicholson, C., Iliff, J.J., Takano, T., Deane, R., Nedergaard M. Sleep Drives Metabolite Clearance from the Adult Brain.. Science 18 Oct 2013: Vol. 342, Issue 6156, pp. 373-377
Nedergaard M. Neuroscience. Garbage truck of the brain. Science. 2013 Jun 28;340(6140):1529-30.
Louvain, A., Smirnov, S., Keyes, T.J., Eccles, J.D., Rouhani, S.J, Peske, J.D., Derecki, N.C., Castle, D., Mandell, J.W., Lee, K.S., Harris, T.H., Kipnis, J. (2015). “Structural and functional features of central nervous system lymphatic vessels” ‘Nature’.
Breslow, J. M. 76 of 79 Deceased NFL Players Found to Have Brain Disease. Frontline, Sept. 2014
Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson DA, McLean AJ. Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet. 1994;344:1055–1056.
Bergsneider M, Hovda DA, Lee SM, et al. Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury. J Neurotrauma. 2000;17:389–401
Yamakami I, McIntosh TK. Effects of traumatic brain injury on regional cerebral blood flow in rats as measured with radiolabeled microspheres. J Cereb Blood Flow Metab. 1989;9:117–124
Cifu, D.X., Drake D.F., Steinmetz B.D. Repetitive Head Injury Syndrome, Medscape, 2014
Mckee AC, Daneshvar DH. The neuropathology of traumatic brain injury. Handb Clin Neurol. 2015;127:45-66.
Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders,” by Carlo Ballatorre, Virginia M.-Y. Lee, and John Q. Trojanowski, Nature Reviews Neuroscience 2007 Vol 8 (9), Sept: 663-72.
Boris Prilutsly, LMT, MA
Mr. Prilutsky, has practiced and taught Medical and Sports Massage for more than 40 years. He has a master’s degree in physical education and rehabilitation from Ukraine. Mr. Prilutsky has worked with athletes and world dignitaries throughout Europe, Israel and the USA.
During the last 3 years he noticed a significant increase in the number of postconcussion patients in his clinic. Mr. Prilutsky understands the great need for therapists to use the correct way to handle their rehabilitations and now he shares his clinical expertise with therapists in JMS and nationally.
REFERENCES
Ballatorre, C., Lee, V.M.Y., Trojanowski, J.Q, Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders, Nature Reviews Neuroscience 2007 Vol 8 (9), Sept: 663-72.
Bergsneider M, Hovda DA, Lee SM, et al. Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury. J Neurotrauma. 2000;17:389–401
Boden BP, Tacchetti RL, Cantu RC, Knowles SB, Mueller FO. Catastrophic head injuries in high school and college football players. Am J Sports Med. 2007 Jul. 35(7):1075-81
Breslow, J. M. 76 of 79 Deceased NFL Players Found to Have Brain Disease. Frontline, Sept. 2014
Cifu, D.X., Drake D.F., Steinmetz B.D. Repetitive Head Injury Syndrome, Medscape, 2014
Giza CC, Hovda DA (2001) The neurometabolic cascade of concussion. J Athl
Train 36: 228–235.
Gerson J, Castillo-Carranza DL, Sengupta U, Bodani R, Prough DS, DeWitt DS, Hawkins BE, Kayed R. Tau Oligomers Derived from Traumatic Brain Injury Cause Cognitive Impairment and Accelerate Onset of Pathology in Htau Mice. J Neurotrauma. 2016 Apr 22.
Louvain, A., Smirnov, S., Keyes, T.J., Eccles, J.D., Rouhani, S.J, Peske, J.D., Derecki, N.C., Castle, D., Mandell, J.W., Lee, K.S., Harris, T.H., Kipnis, J. (2015). “Structural and functional features of central nervous system lymphatic vessels” ‘Nature’.
Mckee AC, Daneshvar DH. The neuropathology of traumatic brain injury. Handb Clin Neurol. 2015;127:45-66.
Meyer KS, Marion DW, Coronel H, Jaffee MS. Combat-related traumatic brain injury and its implications to military healthcare. Psychiatr Clin North Am. 2010 Dec. 33(4):783-96.
Nedergaard M. Neuroscience. Garbage truck of the brain. Science. 2013 Jun 28;340(6140):1529-30.
Yamakami I, McIntosh TK. Effects of traumatic brain injury on regional cerebral blood flow in rats as measured with radiolabeled microspheres. J Cereb Blood Flow Metab. 1989;9:117–124
Xie, L., Kang, H., Xu,Q., Chen, M.J., Liao, L., Thiyagarajan, M., O’Donnell, J., Christensen, D.J., Nicholson, C., Iliff, J.J., Takano, T., Deane, R., Nedergaard M. Sleep Drives Metabolite Clearance from the Adult Brain.. Science 18 Oct 2013: Vol. 342, Issue 6156, pp. 373-377
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