Concussion in Sport

March 2, 2017


A heavily debated topic within sports medicine today is whether or not prior concussion/mTBI increases one’s risk of sustaining a musculoskeletal injury. Most recognize that there is a link between concussion and musculoskeletal injury. Which comes first, the concussion or the risk of injury? Basically, which comes first, the chicken or the egg? To answer this question, we must first start with the series of neurometabolic changes that occur immediately following a mTBI.

For the purpose of this discussion let’s think of neurons like eggs suspended in a jar of water.

The initial injury is just like any other soft tissue injury. Cellular membranes become damaged and intracellular contents escape into the extracellular space. Within the brain this cellular damage is the result of axonal stretching and opening of voltage dependent K+ channels.1,2 Basically someone just dropped our jar, the egg got tossed around, and now the shell is cracked. In turn yolk is leaking into the water and water is leaking into the yolk. In the brain this is observed as an K+ efflux, and Ca2+ influx at the cellular level.1,2 This efflux of extracellular K+ triggers an indiscriminate release of excitatory amino acid (EAA) glutamate and neuronal depolarization, as indicated by Figure: 1.2 Essentially, neurons begin rapidly shutting down.

The balance in the jar is eventually re-established but not without a cost.

In response to neuronal depolarization, a temporary positive feedback loop is established. Additional release of EAAs occurs and triggers the opening of EAA receptor channels as well as the release of even more K+ into the extracellular space.1 This “ionic flux and depolarization can then trigger voltage- or ligand-gated ion channels, creating a diffuse ‘spreading depression-like’ state that may be the biological substrate for very acute post-concussive impairments”.2


This cascading disturbance in ionic homeostasis is combated by over utilization of ATP requiring-membrane ionic pumps. As a result, “hyperglycoloysis, relative depletion of intracellular energy reserves, and an increase in ADP”2 is observed. Additionally, the prolonged intracellular calciu
m flux observed in Figure 2 is mediated by mitochondrial uptake and thus, potentially given rise to mitochondrial dysfunction.2 If mitochondrial dysfunction does occur, this can result in oxidative metabolism disturbances and subsequent alterations of the intracellular redox state. “This puts additional stress on the system by generative damaging free radicals and shifting metabolic pathways that can trigger longer-lasting impairments and set the stage for vulnerability to repeated injury”.2

So why do we see such a prolonged increase in calcium levels?

To begin to answer this question, let us first start with an overview of oligodendrocytes. Oligodendrocytes are specialized glial cells “which speed up conduction by enveloping the axonal projections in a multilayered membrane sheath called myelin”.3 They’re light the rubber that covers a copper wire. As indicated by Figure 2, K+ levels rise to nearly 450% above baseline following a mTBI. This increase in extracellular K+ is toxic to the surrounding cells, and one such cell that is susceptible to a rise in extracellular K+ is oligodendrocytes. “Increased K+ levels trigger an intracellular rise in hydrogen ions (H+). This reduces the pH in the cell, activating TRPA1-channel proteins and leading to an influx of calcium ions (Ca2+). High levels of Ca2+ are toxic to oligodendrocytes and damage myelin” (Figure 3).4 It could be hypothesized that this influx of intracellular Ca2+ and subsequent oligodendrocyte damage gives rise to the prolonged extracellular influx of Ca 2+ observed shortly after the resolve of extracellular K+ levels in Figure 2. Basically, K+ is like a Trojan Horse that enters the oligodendrocyte then opens up the doors for Ca2+ to enter and kill everything, thus destroying the trade routes of the brain.

According to research, “diffusion tensor imaging (DTI) fractional anisotropy (FA) detects abnormalities in multiple white matter tracts (the trade routes) in mild TBI, with the most common changes found in anterior regions of the corona radiata and corpus callosum”.5 Recent studies of mild TBI at the subacute stage (5–18 days post-injury) demonstrate reduced FA in white matter is a useful predictive measure of 3–6 month outcome”.6 This decrease in FA is indicative of demyelination, which is the result of oligodendrocyte dysfunction. It is highly probable that the level of subacute FA is negatively correlated to the level of acute extracellular K+.

So what does the corpus callosum do?

As aforementioned, the white matter of the corpus callosum the trade routes between hemispheres. “The corpus callosum is the brain’s most important connection between cortical areas of both hemispheres. Due to the hemispheric lateralization of brain function, information transfer between both hemispheres is vital for an optimal performance in tasks, in which several psycho-motor functions have to be integrated”.7 Given this knowledge it is alarming that a recent study revealed reduced interhemispheric cortical communication in pediatric patients up to 473 days’ post-concussion.7

This information supports the hypothesis that the physiological effects of a concussion causes white matter damage which then results in neuromechanical deficits that could be related to an increased risk of subsequent musculoskeletal injury for a prolonged period of time.

Going forward, we need to develop strategies to decrease the adverse effects of neuroinflammation and look for potentially early interventions to stimulate remyelination during the sub-acute phase. It comes down to denying the Trojan Horse, preventing the opening of the TRPA-1 gates, minimizing/reversing the effects the damage has had on the trade route.


Post Credit: Christopher Ballance