Traumatic brain injury (TBI), sometimes referred to as the “silent epidemic,” has been identified by the Centers for Disease Control and Prevention (CDC) as a major health concern in the United States [1] and is the leading cause of disability worldwide [2]. Broken down into three grades based upon level of injury and severity, the most common variant of TBI is the mild classification [3, 4]. Mild traumatic brain injury (mTBI), also known by its more common name concussion [5], has an annual incidence in the United States of 1.6–3.8 million cases attributed to sports [1]. Despite the staggering occurrence of sports-related concussions, these mTBIs can be the result of motor vehicle accidents or falls, and have become the dominant war-related injury seen in the military [6]. The mechanical trauma experienced during a single concussive event causes the brain to undergo forceful acceleration and deceleration [7]. This violent shaking of the malleable brain inside the hard, confined spaces of the skull is not only expressed in a linear fashion, but rotational forces associated with a concussion also apply unnecessary axonal strain, leading to diffuse axonal injury (DAI) [8, 9]. Consequently, following a concussive episode, there is a destructive pathophysiological response that initiates a complex chain of neurometabolic and neurochemical reactions.

Due to the biochemical sequelae that follow a concussion, individuals present with a constellation of symptoms that can include physical, cognitive, and emotional manifestations [3, 10]. Some of the most common clinical symptoms include headache, nausea, visual disturbances, light sensitivity, dizziness, fatigue, poor concentration, short-term memory loss, unsteady gait, and irritability [10]. These persistent symptoms from concussion can lead to post-concussive syndrome (PCS) and long-term disabilities [11]. For most sports-related concussions, there is spontaneous recovery with resolution of symptoms within 10 days post-injury [12, 13]. However, up to 15 % of individuals recovering from a concussion report symptoms for more than 1 year following insult [14].

Additionally, injury to the brain is also associated with an increased susceptibility to a number of psychiatric conditions, as well as certain neuropathologies [13, 15, 16].

Even with the multitude of signs and symptoms, alterations in the neurochemical environment, and disruption of normal neurometabolic reactions, conventional neuroimaging techniques and neuropsychological tests fail to adequately detect these alterations in the subacute phase of injury [17]. Additionally, these approaches are not always to differentiate individuals who have suffered a previous concussion from those with no history of prior head injury [18]. Making matters worse is a lack of a universally accepted definition of concussion [19] and an objective diagnostic test [20]. The lack of sensitivity and specificity of current clinical measures for concussion management is a major concern as evidenced by the mounting research demonstrating the damaging effects of cumulative concussions and sub-concussive head trauma [15, 21, 22].

Clearly, concussion is not cerebral ischemia, and it is not stroke. Rather, concussion is a mild form of TBI. If you try to apply the same principles in terms of treatment modalities, biomechanics, or physiology between stroke/ischemia and the TBI, this will not work. Concussion and stroke are two separate and quite different pathophysiological entities. There are, however, some overlaps. Both phenomena may result in a regional and temporal cellular alteration and may produce cell death. That means that concussion, as a mild form of TBI characteristically produces cell dysfunction. Particularly, concussion produces a regional alteration of cellular functions and some of those functions can result in cell death or axonal disconnection. As a result, concussion produces a state of energy crisis and subsequence metabolic diaschisis.

Throughout the years, from the early 1990s on, many people have asked me what physiologically causes a concussion. My answer is that it is an injury caused to the brain due to biomechanical forces [7]. These biomechanical forces do not have to come from a direct blow to the head, but can be the result from any forces that are translated to the head. After contact that causes translation acceleration of the head, there is a slight lag experienced by the brain which then impacts the skull. This initial contact of the brain to the skull is known as the coup, and these coup injuries often are in the frontal lobe which makes concussion hard to diagnose clinically and test for on the field. As the brain is accelerated and then recoiled, there are countrecoup injuries that are injuries away from the initial site of impact and can be shearing injuries of axons and cerebral blood vessels [23]. In addition to linear accelerations, shearing injuries can also be caused by the addition of rotational or angular forces experienced by the brain following a concussive blow, especially in the corpus callosum and structures around the third ventricle [23].

Due to the movement of the brain inside the skull that can cause stress and strain on the cellular level, as well as the impact of the brain on the interior of the skull, concussion leads to the disruption of neuronal membranes. Stretched and damaged axons swell and then separate, although most axons initially affected gradually recover with time, and for the most part the pathophysiology of concussion is thought to be neurometabolic [14]. In fact, it is speculated that these sub-concussive impacts can cause microstructural and biochemical changes in the brain similar to full blown concussive episodes just to a lesser extent [24].

The acute effects related to sports-related concussion are usually short lived [25] and for most sports-related concussions there is spontaneous recovery with resolution of symptoms within 10 days post-injury [12]. However, Rutherford et al. reported that over 50 % of the patients recovering from concussion had symptoms lasting up to 6 weeks, with 15 % of individuals reporting symptoms lasting over 1 week [25].

The idea of an energy crisis in acute phase of brain injury as related to diaschisis is an important issue that I would like to elaborate on in more detail. There is still confusion and controversy over what researchers mean when using the term diaschisis. It should be clearly understood that every TBI, regardless of its severity, starts out as a concussive blow. It changes the properties and characteristics of what the brain uses for fuel and energy. For example, if someone drinks a Gatorade this afternoon, the fuel that is in that Gatorade is used in the brain in one way. If someone has a concussion this afternoon, and then uses a Gatorade, this fuel is used in a completely different manner. So the Gatorade that we thought was good for the physiology of the body was not the same as the Gatorade that we thought would be good for the physiology of the brain.

When trying to credit where most of today’s literature about the physiology of concussion comes from, people have attributed a lot of the work primarily to me, my colleagues, and to some of my students. But if you would like to see where the first and explicit paper was published about the physiology of concussion, you have to look at the work of Earl Walker. In 1944, Dr. Walker became very interested with physiology of concussion and worked alongside with Denny Brown. In his seminal paper: “The physiological basis of concussion,” Dr. Walker suggested that concussion produced a depression-like phenomenon [26]. Accordingly, spreading depression was called a mTBI injury. However, I fail to see what is so “mild” about mTBI.

Another important cornerstone and insight on the diaschisis should be attributed to Constantin von Monakow, a Swiss neurologist of Russian extraction. He worked with Broca, whom the speech area of the brain was famously named after, doing research in stroke patients. It is well known that people who have suffered massive strokes in the left hemisphere are aphasic. Aphasic patients cannot speak, though overall look normal. Dr. von Monakow treated numerous neurological patients who had strokes in the right hemispheres resulting in damage to the right part of the brain. These patients became aphasic, but they recovered over time. He described a phenomenon where the brain was not irreversibly, but rather temporarily, damaged. These stroke patients were stunned; their brain was depressed and they were dysfunctional for a period of time. Language disturbances observed in these patients with nondominant hemisphere lesions were not due to a permanent brain damage and instead resolved over a period of time. This observation inspired Dr. von Monakow to propose a clear distinction between what would be a permanent disability versus that which would be temporary neurological dysfunction. The fact that the majority of concussed individuals eventually recover over time, the concussion, as a phenomenon, may be considered as diaschisis. Indeed, von Monakow aimed to distinguish between the transient central nervous system disorders due to suppression of brain activity and the deficits resulting from brain lesions that never disappear.

The concept of diaschisis comes back to the idea of energy supply for the brain. It is well known that approximately 90 % of a person’s energy comes from something called adenosine triphosphate or ATP that is synthesized about 522 A/s. The human body on average makes about 65 kg of ATP per day. On average, you consume about 380 l of oxygen per day. The average human works at about 100 kcal over about 116 W of power per hour. That would be comparable to a dim light bulb.

The brain contributes up to 2–4 % of the human body mass, but takes up about 20 % of the total energy demands. Most of the energy the brain consumes comes from ATP. The lack of energy supplies and the high demands for fuel in acute phase of TBI results in energy crisis, the concept that I would like to elaborate in more detail in the following text. In order to understand the importance of the energy crisis after mTBI, I have to convince you that it takes energy to live and make the brain functional. I am also going to convince you that it takes energy and sufficient time to recover from brain injury regardless of its severity.

The most common experimental procedure to study TBI in animals is a fluid percussion device. This fluid percussion device is a saline filled cylinder attached to the experimental animal via a craniectomy. By then striking one end of the cylinder with a pendulum, a small amount of volume of fluid is introduced to the cranial cavity, outside of the dura. This action moves the brain a certain distance at a certain velocity. This particular procedure was developed years ago by Gurdjian and is still a valuable tool to study traumatic brain injuries in a well-controlled environment. Instead of taking the head and shaking it violently causing the brain to move, the fluid percussion device will move the brain in a systematic way inside the head. In order to understand the pathophysiological mechanisms underlying the effect of brain motion induced by fluid percussion, a special technique called cerebral microdialysishas been developed. It is a fancy term for putting a small catheter in the brain and is done both in humans and in animals. This procedure allows researchers to dialyze the extracellular space and it works the same way as if blood is dialyzed. It can also measure the concentration of neurochemical substances in the extracellular space.

Immediately after a concussion, a destructive biochemical response ensues that initiates a chain of neurometabolic and neurochemical reactions that include activation of inflammatory responses, imbalances of ion concentrations, increase in the presence of excitatory amino acids, dysregulation of neurotransmitter synthesis and release, and production of free radicals [27]. As outlined by Giza and Hovda [28], the pathophysiological response to concussion is a complex combination of changes in the brain at a vascular and cellular level. As a result from the trauma, the brain undergoes disruptions in neurochemical and neurometabolic homeostasis. This disruption via a physical tearing or shearing of the membrane itself is also compounded by the deregulation of selective ion channels.